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preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style"><div class="fm-sec bkr_bottom_sep"><div class="bkr_thumb"><a href="https://www.nice.org.uk" title="National Institute for Health and Care Excellence (NICE)" class="img_link icnblk_img" ref="pagearea=logo&targetsite=external&targetcat=link&targettype=publisher"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-niceng187er1-lrg.png" alt="Cover of Evidence reviews for the use of vitamin D supplementation as prevention and treatment of COVID-19" /></a></div><div class="bkr_bib"><h1 id="_NBK566064_"><span itemprop="name">Evidence reviews for the use of vitamin D supplementation as prevention and treatment of COVID-19</span></h1><div class="subtitle">Vitamin D for COVID-19</div><p><b>Evidence review A</b></p><p><i>NICE Guideline, No. 187</i></p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2020 Dec</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-3942-8</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2020.</div></div><div class="bkr_clear"></div></div><div id="niceng187er1.s1"><h2 id="_niceng187er1_s1_">1. Vitamin D for COVID-19 prevention and treatment</h2><div id="niceng187er1.s1.1"><h3>1.1. Review question</h3><p>
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<b>What is the clinical effectiveness and safety of vitamin D supplementation for the treatment of COVID-19 in adults, young people and children?</b>
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</p><div id="niceng187er1.s1.1.1"><h4>1.1.1. Introduction</h4><p>Vitamin D is hypothesised to have a role in the immune response to respiratory viruses and can potentially mitigate the inflammatory response. During the COVID-19 pandemic, treatments are being explored as options for managing the disease. Therefore, it has been suggested vitamin D could improve outcomes in people diagnosed with confirmed COVID-19. The 2 major forms of vitamin D, vitamin D<sub>3</sub> (cholecalciferol) and vitamin D<sub>2</sub> (ergocalciferol), are licensed for the prevention and treatment of vitamin D deficiency and are taken by many people who have vitamin D deficiency. The review aims to assess if vitamin D can be used in all people regardless of vitamin D status as a safe treatment option, alone or in combination with other therapies, to treat COVID-19.</p></div><div id="niceng187er1.s1.1.2"><h4>1.1.2. Summary of the protocol</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1tab1"><a href="/books/NBK566064/table/niceng187er1.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1tab1" rid-ob="figobniceng187er1tab1"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.tab1/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.tab1/?report=previmg" alt="Table 1. PICO table for review question 1." /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.tab1"><a href="/books/NBK566064/table/niceng187er1.tab1/?report=objectonly" target="object" rid-ob="figobniceng187er1tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">PICO table for review question 1. </p></div></div></div><div id="niceng187er1.s1.1.3"><h4>1.1.3. Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng187er1.appa">appendix A</a>.</p><p>Risk of bias in randomised controlled trials was assessed by using the Cochrane risk of bias tool (2.0). Results of the risk of bias assessments can be found alongside the evidence table for each study (<a href="#niceng187er1.appd.s1.1">Appendix D.1.1</a>). Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to present results and to evaluate the quality of evidence by outcomes (see <a href="#niceng187er1.appe">Appendix E</a>). GRADE assessment domains include risk of bias, inconsistency, indirectness, and imprecision. Outcomes start at High, for example, for a randomised controlled trial, and can be marked down 1 or 2 levels for each domain through to Moderate, Low and Very Low evidence. Each of the evidence quality ratings are explained below:</p><p>High – Further research is very unlikely to change our confidence in the estimate of effect.</p><p>Moderate – Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.</p><p>Low – Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.</p><p>Very low – Any estimate of effect is very uncertain.</p><p><a href="https://www.nice.org.uk/guidance/ng187/history" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Declarations of interest</a> of the expert panel members who developed the guideline recommendations were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng187er1.s1.1.4"><h4>1.1.4. Effectiveness evidence</h4><div id="niceng187er1.s1.1.4.1"><h5>1.1.4.1. Included studies</h5><p>One search was conducted for all 3 reviews questions, which returned 640 results. For review question 1, after screening, 3 were considered at full text and 1 study was included.</p></div><div id="niceng187er1.s1.1.4.2"><h5>1.1.4.2. Excluded studies</h5><p>Three studies were screened at full text; the 2 excluded studies can be found in <a href="#niceng187er1.appg">Appendix G</a>.</p></div></div><div id="niceng187er1.s1.1.5"><h4>1.1.5. Summary of studies included in the effectiveness and prognostic evidence</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1tab2"><a href="/books/NBK566064/table/niceng187er1.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1tab2" rid-ob="figobniceng187er1tab2"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.tab2/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.tab2/?report=previmg" alt="Table 2. Summary of studies included in the evidence review." /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.tab2"><a href="/books/NBK566064/table/niceng187er1.tab2/?report=objectonly" target="object" rid-ob="figobniceng187er1tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of studies included in the evidence review. </p></div></div><p>See <a href="#niceng187er1.appd.s1">appendix D.1</a> for full evidence tables.</p></div><div id="niceng187er1.s1.1.6"><h4>1.1.6. Summary of the effectiveness evidence</h4><p>One study reported 2 outcomes concerning people who had been admitted to hospital with COVID-19: admission to intensive care and mortality. Evidence quality was graded as very low because of a very serious risk of bias and the low number of participants in the study (n=76).</p><p>The number of people who were admitted to ICU in the calcifediol arm (n=50) was 1 (2%) and in the standard care only arm (n=26) was 13 (50%). An adjusted multivariable model reported that people who received calcifediol treatment plus standard care were less likely to be admitted to intensive care than people who received standard care only, OR 0.03 (95% CI 0.003 to 0.25) [adjusted for hypertension and diabetes as prevalence differed between arms].</p><p>Mortality was reported as number of deaths. There were 0 deaths in the calcifediol treatment plus standard care arm and 2 deaths in the standard care only arm, (OR 0.097, 95%CI 0.004 to 2.099).</p><p>See <a href="#niceng187er1.appe">appendix E</a> for full GRADE tables.</p></div><div id="niceng187er1.s1.1.7"><h4>1.1.7. Economic evidence</h4><p>Economic evidence was not considered for this review.</p></div></div><div id="niceng187er1.s1.2"><h3>1.2. Review question</h3><p>
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<b>What is the clinical effectiveness and safety of vitamin D supplementation for the prevention of SARS CoV2 infection (and subsequent COVID-19) in adults, young people and children?</b>
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</p><div id="niceng187er1.s1.2.1"><h4>1.2.1. Introduction</h4><p>The current COVID-19 pandemic is caused by transmission of SARS-CoV-2 between people. Lowering the infection rate is important in keeping hospital admissions manageable and preventing death and illness. A range of different approaches have been taken for lowering the infection rate. One option that has been suggested is vitamin D supplementation because it has been hypothesised to be involved in the body’s immune response and could mitigate the inflammatory response. This review aims to assess if vitamin D supplementation can prevent SARS CoV2 infection and subsequent COVID-19.</p></div><div id="niceng187er1.s1.2.2"><h4>1.2.2. Summary of the protocol</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1tab3"><a href="/books/NBK566064/table/niceng187er1.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1tab3" rid-ob="figobniceng187er1tab3"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.tab3/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.tab3/?report=previmg" alt="Table 3. PICO table for review question 2." /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.tab3"><a href="/books/NBK566064/table/niceng187er1.tab3/?report=objectonly" target="object" rid-ob="figobniceng187er1tab3">Table 3</a></h4><p class="float-caption no_bottom_margin">PICO table for review question 2. </p></div></div></div><div id="niceng187er1.s1.2.3"><h4>1.2.3. Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng187er1.appa">appendix A</a>.</p><p>Risk of bias in randomised controlled trials was assessed by using the Cochrane risk of bias tool (2.0). Results of the risk of bias assessments can be found alongside the evidence table for each study (<a href="#niceng187er1.appd">Appendix D</a>). Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to present results and to evaluate the quality of evidence by outcomes (see <a href="#niceng187er1.appe">Appendix E</a>). GRADE assessment domains include risk of bias, inconsistency, indirectness, and imprecision. Outcomes start at High, for example, from a randomised controlled trial, can be marked down 1 or 2 levels for each domain through to Moderate, Low and Very Low evidence. Each of the evidence quality ratings are explained below:</p><p>High – Further research is very unlikely to change our confidence in the estimate of effect.</p><p>Moderate – Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.</p><p>Low – Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.</p><p>Very low – Any estimate of effect is very uncertain.</p><p><a href="https://www.nice.org.uk/guidance/ng187/history" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Declarations of interest</a> of the expert panel members who developed the guideline recommendations were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng187er1.s1.2.4"><h4>1.2.4. Effectiveness evidence</h4><div id="niceng187er1.s1.2.4.1"><h5>1.2.4.1. Included studies</h5><p>One search was conducted for all 3 evidence reviews, which returned 640 results. For review question 2, after screening, 2 studies were at full text considered and no studies were included.</p></div><div id="niceng187er1.s1.2.4.2"><h5>1.2.4.2. Excluded studies</h5><p>Two studies were considered at full text. All were excluded and can be found with reasons in <a href="#niceng187er1.appg">Appendix G</a>.</p></div></div><div id="niceng187er1.s1.2.5"><h4>1.2.5. Summary of the effectiveness evidence</h4><p>No evidence relevant to the protocol was found for this question.</p></div><div id="niceng187er1.s1.2.6"><h4>1.2.6. Economic evidence</h4><p>Economic evidence was not considered for this review.</p></div></div><div id="niceng187er1.s1.3"><h3>1.3. Review question</h3><p>
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<b>Is vitamin D status independently associated with susceptibility to developing COVID-19, severity of COVID-19, and poorer outcomes from COVID-19 in adults, young people and children?</b>
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</p><div id="niceng187er1.s1.3.1"><h4>1.3.1. Introduction</h4><p>The COVID-19 pandemic has affected countries differently. Some have hypothesised that the differences are in part caused by people’s vitamin D status. It has also been suggested that the higher incidence of SARS CoV2 infection in older people and ethnic minorities could be partly explained by lower serum vitamin D, which is more common in these groups. The aim of this review is to assess if there is an association between vitamin D status and incidence of SARS CoV2 infection, poorer outcomes, and COVID-19 severity.</p></div><div id="niceng187er1.s1.3.2"><h4>1.3.2. Summary of the protocol</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1tab4"><a href="/books/NBK566064/table/niceng187er1.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1tab4" rid-ob="figobniceng187er1tab4"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.tab4/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.tab4/?report=previmg" alt="Table 4. protocol summary for review question 3." /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.tab4"><a href="/books/NBK566064/table/niceng187er1.tab4/?report=objectonly" target="object" rid-ob="figobniceng187er1tab4">Table 4</a></h4><p class="float-caption no_bottom_margin">protocol summary for review question 3. </p></div></div></div><div id="niceng187er1.s1.3.3"><h4>1.3.3. Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng187er1.appa">appendix A</a>.</p><p>Studies included in this review were anticipated to be cohort, case-control and cross-sectional designs analysing associations between vitamin D using regression adjusting for confounding variables. Regression analyses reveal relationships among variables and adjustment attempts to eliminate the effect of other factors to assess if the variable in question is independently associated with an outcome. In the example of vitamin D, older people have low vitamin D and poorer COVID-19 outcomes. A regression analysis without any adjustment will not infer whether age or vitamin D, or both, are associated with poorer COVID-19 outcomes. A regression model adjusted for age will allow us to see associations, including vitamin D, that are not due to age. This can be done with numerous measurable variables but does not mean that all factors have been accounted for. Many other factors are associated both with COVID-19 outcomes and with vitamin D status, for example obesity, ethnicity, diabetes, socioeconomic status, household crowding and urban place of residence. For this reason, only studies that reported multivariable (adjusted) models for outcomes of interest were considered because at least some confounding variables are considered in these models.</p><p>However, it is noteworthy that associations demonstrated in an adjusted model do not imply that the relationships are causal. There are other factors that could be influencing the association that were not adjusted for. Association should not be confused with causality. This is especially important when many variables are studied in a complex public health scenario. In this scenario spurious associations can arise because the large number of factors studies makes it possible that an association could be discovered by chance or because of multicollinearity, explored below.</p><p>Studies on associations can be used to form the basis for hypothesis testing for causality. Therefore, association studies are usually published to inform future research. It was not expected that many published RCTs would be available for vitamin D as treatment or prevention at this stage of the pandemic. This is because association studies can generate hypotheses and guide timely and costly RCTs. However, there are a number of methodological and statistical considerations that need to be taken into account when interpreting findings from association studies. Firstly, to assess whether there is a confirmed or scientifically proven biological plausibility between the dependent variable and outcome of interest. Caution is required if the hypothesis of the relationship is based on indirect association, that is if A is caused by B, A is similar to C, therefore C must also be caused by B.</p><p>Another consideration that needs careful interpretation in any multivariable analysis is the issue of multicollinearity, meaning 2 or more variables are associated with each other. The mediating and moderating effect from other variables (for example confounding variables or other independent variables in the model) need to be explored before concluding the association between the dependent variable and outcome of interest. This is because the model assumption that a change in the independent variable will lead to a change in the dependent variable while all other variables are held constant will be violated. Without these considerations, estimates for this association will be imprecise and small changes to the raw data may generate large changes to the model results.</p><p>There are also several statistical principles in multivariable analysis that are either not commonly conducted by researchers or poorly reported. For example, the lack of goodness-of-fit testing, lack of residual analysis, the family-wise error rate (due to multiple comparisons in a multivariable model) is not adjusted, violation of assumption of normality, lack of cross-validation, and others. All data was extracted from the studies in relation to these principles, where available.</p><p>All the elements above need careful assessment in order to decide the quality of the study and whether the concluded association is valid. As the studies that were included were looking at association, the risk of bias checklist used was the QUIPS checklist. This checklist has domains that considers the above issues. A modified version of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to present results and to evaluate the quality of evidence by outcomes (see <a href="#niceng187er1.appe">Appendix E</a>). Only outcomes that had been adjusted for covariates were presented, all conducted through multivariable analysis. When unadjusted (univariable) values were presented, they were included in the modified GRADE table for reference. In modified GRADE, the assessment domains include risk of bias, inconsistency, indirectness, and imprecision. For observational studies, outcomes start at Low (for example, cohort study and case control study) can be marked down 1 or 2 levels for each domain through to Very Low evidence. Evidence quality can be raised 1 or levels in specific circumstances: if the effect estimate is large or if the effect shows a dose-response curve. Each of the evidence quality ratings are explained below:</p><p>High – Further research is very unlikely to change our confidence in the estimate of effect.</p><p>Moderate – Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.</p><p>Low – Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.</p><p>Very low – Any estimate of effect is very uncertain.</p><p><a href="https://www.nice.org.uk/guidance/ng187/history" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Declarations of interest</a> of the expert panel members who developed the guideline recommendations were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng187er1.s1.3.4"><h4>1.3.4. Association evidence</h4><div id="niceng187er1.s1.3.4.1"><h5>1.3.4.1. Included studies</h5><p>One search was conducted for all 3 evidence reviews, which returned 640 results. For review question 3, after screening, 69 studies were considered at full text and 12 studies were included.</p><p>Twelve studies were identified as pre-prints and listed as references but data was not extracted from them for this review as they have not yet been peer reviewed. One extra study in preprint was identified through stakeholder consultation and included in the list of preprints. This made a total of 13 preprint studies.</p></div><div id="niceng187er1.s1.3.4.2"><h5>1.3.4.2. Excluded studies</h5><p>Sixty-nine studies were considered at full text. Forty-five were excluded; reasons for exclusion can be found in <a href="#niceng187er1.appg">Appendix G</a>.</p></div></div><div id="niceng187er1.s1.3.5"><h4>1.3.5. Summary of studies included in the effectiveness and prognostic evidence</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1tab5"><a href="/books/NBK566064/table/niceng187er1.tab5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1tab5" rid-ob="figobniceng187er1tab5"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.tab5/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.tab5/?report=previmg" alt="Table 5. Summary of studies included in the evidence review." /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.tab5"><a href="/books/NBK566064/table/niceng187er1.tab5/?report=objectonly" target="object" rid-ob="figobniceng187er1tab5">Table 5</a></h4><p class="float-caption no_bottom_margin">Summary of studies included in the evidence review. </p></div></div><p>See <a href="#niceng187er1.appd.s2">appendix D.2</a> for full evidence tables.</p></div><div id="niceng187er1.s1.3.6"><h4>1.3.6. Summary of the association evidence</h4><p>Twelve studies reported on how vitamin D status associated with COVID-19 outcomes. Outcomes included COVID-19 cases, COVID-19 severity including hospitalisation and mechanical ventilation, and mortality. Studies reported vitamin D status differently. Some measured associations between outcomes and linear vitamin D concentrations. Whereas others used cut-offs to define deficiency and assessed the risk of an outcome by comparing people considered vitamin D deficient and vitamin D sufficient. All outcomes were rated as very low quality of evidence. Evidence was downgraded for high risk of bias, indirectness, and imprecision due to the number of factors adjusted and low participant numbers.</p><div id="niceng187er1.s1.3.6.1"><h5>Association between vitamin D status and COVID-19 cases</h5><p>Six studies explored the association between vitamin D status and COVID-19 incidence. Some studies found a negative association between vitamin D status and COVID-19 incidence. Whether studies measured vitamin D as a linear scale or compared people with vitamin D deficiency to people without did not have an impact on whether a significant association was found.</p><p>Three studies assessed the linear association between vitamin D concentration measured and the risk of COVID-19 cases and 1 found a significant association, OR 0.984 (95% CI 0.983 to 0.986) N=191,779 (<a class="bibr" href="#niceng187er1.s1.3.ref7" rid="niceng187er1.s1.3.ref7">Kaufman 2020</a>). Conversely, another study did not find an association, OR 1.00 (0.998 to 1.01) N=349,017 (<a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>). This study also demonstrated that ethnicity did not impact on the association between vitamin D status and COVID-19 cases. However, it is difficult to provide a definite effect estimate due to lack of power in this analysis. <a class="bibr" href="#niceng187er1.s1.3.ref12" rid="niceng187er1.s1.3.ref12">Raisi-Esrabragh 2020</a> used the same UK Biobank database for their analysis as <a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>. There was no association found between vitamin D status COVID-19 cases, OR 1.00 (1.00 to 1.00), N=4510. However, the UK Biobank study measured serum vitamin D during initial recruitment in 2006–2010. Serum vitamin D fluctuates and a lag of at least 10 years means the recorded concentrations may not be reflective of current concentrations. <a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a> and <a class="bibr" href="#niceng187er1.s1.3.ref7" rid="niceng187er1.s1.3.ref7">Kaufman 2020</a> used data from everyone that was available in their databases, but <a class="bibr" href="#niceng187er1.s1.3.ref12" rid="niceng187er1.s1.3.ref12">Raisi-Esrabragh 2020</a> only used data from people who had taken a SARS CoV2 test. The difference between the results of the studies that used the UK Biobank data and the Kaufman study may have arisen between the two populations that are included in the analyses. The UK Biobank data has a lower proportion of ethnic minorities and includes a more people from higher socioeconomic groups.</p><p>Within the same study, <a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a> also assessed association between receiving a positive COVID-19 test in 2 groups, people who were vitamin D deficient (<25nmol/L) and people who were insufficient (<50nmol/L) were compared with people with serum concentrations above the thresholds. Both analyses showed no difference in COVID-19 cases between people above and below the thresholds, <25nmol/L OR 0.92 (95% CI 0.71 to 1.21), <50nmol/L OR 0.88 (95% CI 0.72 to 1.08). <a class="bibr" href="#niceng187er1.s1.3.ref9" rid="niceng187er1.s1.3.ref9">Meltzer 2020</a> used the same threshold for deficiency, <50nmol/L and demonstrated an association between vitamin D deficiency and COVID-19 cases, OR 1.77 (95% CI 1.12 to 2.81). However, this study did not adjust for demographic factors, such as sex, gender and ethnicity, that are known to have an impact on COVID-19 case rates. <a class="bibr" href="#niceng187er1.s1.3.ref10" rid="niceng187er1.s1.3.ref10">Merzon 2020</a> did control for demographic variables and found that people with suboptimal serum vitamin D (<75nmol/L) were more likely to contract COVID-19 than people above the threshold OR 1.5 (95% CI 1.13 to 1.98).</p><p>Effects are presented as OR/HR (95% CI) in <a class="figpopup" href="/books/NBK566064/table/niceng187er1.tab6/?report=objectonly" target="object" rid-figpopup="figniceng187er1tab6" rid-ob="figobniceng187er1tab6">Table 6</a> unless otherwise stated.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1tab6"><a href="/books/NBK566064/table/niceng187er1.tab6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1tab6" rid-ob="figobniceng187er1tab6"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.tab6/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.tab6/?report=previmg" alt="Table 6. Summary of evidence for the association between vitamin D status and COVID-19 cases." /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.tab6"><a href="/books/NBK566064/table/niceng187er1.tab6/?report=objectonly" target="object" rid-ob="figobniceng187er1tab6">Table 6</a></h4><p class="float-caption no_bottom_margin">Summary of evidence for the association between vitamin D status and COVID-19 cases. </p></div></div></div><div id="niceng187er1.s1.3.6.2"><h5>Association between vitamin D status and COVID-19 severity</h5><p>Seven studies reported on the association between vitamin D status and COVID-19 severity. Measures for severity included the WHO Ordinal Scale for Clinical Improvement (OSCI) score, composite outcomes, mortality, and hospitalisation.</p><p>Two studies report on composite outcomes. <a class="bibr" href="#niceng187er1.s1.3.ref5" rid="niceng187er1.s1.3.ref5">Hernandez 2020</a> did not find a significant association between vitamin D level in nmol/L and the composite outcome of admission to the intensive care unit (ICU), requirement for mechanical ventilation, or in-hospital mortality, OR 1.13 (95% CI 0.27 to 4.77), n=197. <a class="bibr" href="#niceng187er1.s1.3.ref8" rid="niceng187er1.s1.3.ref8">Macaya 2020</a> also did not find an association between vitamin D deficiency (<50nmol/L) and the composite outcome death, admission to ICU, and/or need for higher oxygen flow than that provided by a nasal cannula, OR 3.2 (95% CI 0.99 to 11.4). <a class="bibr" href="#niceng187er1.s1.3.ref11" rid="niceng187er1.s1.3.ref11">Radujkovic 2020</a> did find a significant association between suboptimal vitamin D (<30 nmol/L) and the composite outcome mechanical ventilation and death, HR 6.12 (95% CI 2.79 to 13.42), n=185. The difference between these studies may lie in which factors were adjusted for in the multivariable analysis.</p><p>Results associating vitamin D status with COVID-19 severity scores were mixed. <a class="bibr" href="#niceng187er1.s1.3.ref13" rid="niceng187er1.s1.3.ref13">Ye 2020</a> used the guidelines of the National Health Commission of China to define severe/critical cases. The study found an association between vitamin D deficiency and severe/critical COVID-19, OR 15.18 (95% CI 1.23 to 187.45). Annweiler 2020a used OSCI scores ≥5 to define severe COVID-19 and included 3 groups: people classed as vitamin D sufficient if they received supplements for a year before COVID-19 diagnosis, people who received vitamin D bolus when diagnosed with COVID-19, and people who had not received any supplementation. Compared with no supplementation, supplementation for a year was significantly negatively associated with having severe COVID-19, OR 0.08 (95% CI 0.01 to 0.81), but there was no difference when only receiving a bolus when diagnosed, OR 0.46 (95% CI 0.07 to 2.85).</p><p>Four studies reported mortality as a standalone outcome. 3 studies found that a higher measured vitamin D status (<a class="bibr" href="#niceng187er1.s1.3.ref6" rid="niceng187er1.s1.3.ref6">Karahan 2020</a>, linear vitamin D measurement) or supplementation before diagnosis (<a class="bibr" href="#niceng187er1.s1.3.ref2" rid="niceng187er1.s1.3.ref2">Annweiler 2020</a>, within a month before or up to a week after diagnosis; Annweiler 2020a, supplemented for a year before diagnosis) were negatively associated with death post COVID-19 diagnosis, OR 0.92 (95% CI 0.88 to 0.98), HR 0.11 (95% CI 0.03 to 0.48) and HR 0.07 (95% CI 0.01 to 0.61, respectively. <a class="bibr" href="#niceng187er1.s1.3.ref11" rid="niceng187er1.s1.3.ref11">Radujkovic 2020</a> also found that suboptimal serum vitamin D (<30nmol/L) was associated with higher mortality rate, HR 14.73 (95% CI 4.16 to 52.19). However, receiving a vitamin D bolus when diagnosed with COVID-19 was as associated with death as no supplementation (HR 0.37 (95% CI 0.06 to 2.21), Annweiler 2020a).</p><p>Hospitalisation for COVID-19 symptoms was reported as a standalone outcome in 1 study (<a class="bibr" href="#niceng187er1.s1.3.ref10" rid="niceng187er1.s1.3.ref10">Merzon 2020</a>). Suboptimal vitamin D levels (<75 nmol/L) were as associated with hospitalisation as higher vitamin D, OR 1.95 (95% CI 0.99 to 4.78).</p><p>Effects are presented as OR/HR (95% CI) in <a class="figpopup" href="/books/NBK566064/table/niceng187er1.tab7/?report=objectonly" target="object" rid-figpopup="figniceng187er1tab7" rid-ob="figobniceng187er1tab7">table 7</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1tab7"><a href="/books/NBK566064/table/niceng187er1.tab7/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1tab7" rid-ob="figobniceng187er1tab7"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.tab7/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.tab7/?report=previmg" alt="Table 7. Summary of evidence for the association between vitamin D status and COVID-19 severity." /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.tab7"><a href="/books/NBK566064/table/niceng187er1.tab7/?report=objectonly" target="object" rid-ob="figobniceng187er1tab7">Table 7</a></h4><p class="float-caption no_bottom_margin">Summary of evidence for the association between vitamin D status and COVID-19 severity. </p></div></div><p>See <a href="#niceng187er1.appe">appendix E</a> for full GRADE tables.</p></div></div><div id="niceng187er1.s1.3.7"><h4>1.3.7. Economic evidence</h4><p>No economic evidence was considered for this review.</p></div><div id="niceng187er1.s1.3.rl.r1"><h4>1.3.9. References – included studies</h4><ul class="simple-list"><div id="niceng187er1.s1.3.rl.r1.1"><h5>1.3.9.1. Treatment</h5><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref1">Entrenas Castillo, Marta, Entrenas Costa, Luis Manuel, Vaquero Barrios, José Manuel
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et al. (2020) “Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”;. J Steroid Biochem Mol Biol
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203: 105751–105751 [<a href="/pmc/articles/PMC7456194/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7456194</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32871238" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32871238</span></a>]</div></p></li></ul></div><div id="niceng187er1.s1.3.rl.r1.2"><h5>1.3.9.2. Association</h5><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref2">Annweiler, Cedric, Hanotte, Berangere, de l’Eprevier, Claire Grandin
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et al. (2020) Vitamin D and survival in COVID-19 patients: A quasi-experimental study. The Journal of steroid biochemistry and molecular biology: 105771 [<a href="/pmc/articles/PMC7553119/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7553119</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33065275" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33065275</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref3">Annweiler, Gaelle, Corvaisier, Mathieu, Gautier, Jennifer
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et al. (2020) Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study. Nutrients
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12(11) [<a href="/pmc/articles/PMC7693938/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7693938</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33147894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33147894</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref4">Hastie, Claire E, Mackay, Daniel F, Ho, Frederick
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et al. (2020) Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes & metabolic syndrome
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14(4): 561–565 [<a href="/pmc/articles/PMC7204679/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7204679</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32413819" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32413819</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref5">Hernandez, JL, Nan, D, Fernandez-Ayala, M
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et al. (2020) Vitamin D Status in Hospitalized Patients With SARS-CoV-2 Infection. The Journal of Clinical Endocrinology & Metabolism</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref6">Karahan, S. and Katkat, F. (2020) Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey. Journal of Nutrition, Health and Aging [<a href="/pmc/articles/PMC7533663/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7533663</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33491033" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33491033</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref7">Kaufman, Harvey W, Niles, Justin K, Kroll, Martin H
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et al. (2020) SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PloS one
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15(9): e0239252 [<a href="/pmc/articles/PMC7498100/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7498100</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32941512" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32941512</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref8">Macaya, Fernando, Espejo Paeres, Carolina, Valls, Adrian
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et al. (2020) Interaction between age and vitamin D deficiency in severe COVID-19 infection. Nutricion hospitalaria
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37(5): 1039–1042 [<a href="https://pubmed.ncbi.nlm.nih.gov/32960622" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32960622</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref9">Meltzer, David O, Best, Thomas J, Zhang, Hui
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et al. (2020) Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA network open
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3(9): e2019722 [<a href="/pmc/articles/PMC7489852/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7489852</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32880651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32880651</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref10">Merzon, Eugene, Tworowski, Dmitry, Gorohovski, Alessandro
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et al. (2020) Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. The FEBS journal [<a href="/pmc/articles/PMC7404739/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7404739</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32700398" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32700398</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref11">Radujkovic, Aleksandar, Hippchen, Theresa, Tiwari-Heckler, Shilpa
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et al. (2020) Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients
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12(9) [<a href="/pmc/articles/PMC7551780/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7551780</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32927735" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32927735</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref12">Raisi-Estabragh, Zahra, McCracken, Celeste, Bethell, Mae S
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et al. (2020) Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank. Journal of public health (Oxford, England)
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42(3): 451–460 [<a href="/pmc/articles/PMC7449237/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7449237</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32556213" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32556213</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref13">Ye, Kun, Tang, Fen, Liao, Xin
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et al. (2020) Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study. Journal of the American College of Nutrition: 1–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/33048028" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33048028</span></a>]</div></p></li></ul></div><div id="niceng187er1.s1.3.rl.r1.3"><h5>1.3.9.3. Other</h5><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref14">Hastie, C.E., Mackay, D.F., Ho, F.
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et al. (2020) Corrigendum to “Vitamin D concentrations and COVID-19 infection in UK Biobank” [Diabetes Metabol Syndr: Clin Res Rev 2020 14 (4) 561–5] (Diabetes & Metabolic Syndrome: Clinical Research & Reviews (2020) 14(4) (561–565), (S1871402120301156), (10.1016/j.dsx.2020.04.050)). Diabetes and Metabolic Syndrome: Clinical Research and Reviews
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14(5): 1315–1316 [<a href="/pmc/articles/PMC7377702/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7377702</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32755828" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32755828</span></a>]</div></p></li></ul></div><div id="niceng187er1.s1.3.rl.r1.4"><h5>1.3.9.4. Pre-prints</h5><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref15">Abu Z M Dayem, Ullah, Lavanya, Sivapalan, Claude, Chelala
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et al. COVID-19 in patients with hepatobiliary and pancreatic diseases in East London: A single-centre cohort study.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref16">Aduragbemi A, Faniyi, Sebastian T, Lugg, Sian E, Faustini
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et al. Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref17">Ariel, Israel, Assi Albert, Cicurel, Ilan, Feldhamer
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et al. The link between vitamin D deficiency and Covid-19 in a large population.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref18">Chang, Timothy S, Ding, Yi, Freund, Malika K
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et al. (2020) Prior diagnoses and medications as risk factors for COVID-19 in a Los Angeles Health System. medRxiv : the preprint server for health sciences</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref19">Claire E, Hastie; Jill P, Pell; Naveed, Sattar
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Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank. [<a href="/pmc/articles/PMC7449523/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7449523</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32851419" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32851419</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref20">Grigorios, Panagiotou, Su Ann, Tee, Yasir, Ihsan
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et al. Low serum 25-hydroxyvitamin D (25D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref21">Isaac Z, Pugach and Sofya, Pugach
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Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe. [<a href="/pmc/articles/PMC7957444/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7957444</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33721102" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33721102</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref22">Jie, Chen, Lixia, Xie, Xing, Yuan
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et al. Low serum vitamin D level and COVID-19 infection and outcomes, a multivariate meta-analysis.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref23">Li, Mengyuan, Zhang, Zhilan, Cao, Wenxiu
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et al. (2020) Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach. The Science of the total environment: 142810 [<a href="/pmc/articles/PMC7550892/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7550892</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33097268" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33097268</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref24">Li
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X, van Geffen
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J, van Weele
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M
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et al. (2020) Genetically-predicted vitamin D status, ambient UVB during the pandemic and COVID-19 risk in UK Biobank: Mendelian Randomisation study.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref25">Mendy, Angelico, Apewokin, Senu, Wells, Anjanette A
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et al. (2020) Factors Associated with Hospitalization and Disease Severity in a Racially and Ethnically Diverse Population of COVID-19 Patients. medRxiv: the preprint server for health sciences</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref26">Panagiotou, G., Tee, S.A., Ihsan, Y.
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et al. (2020) Original publication: Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity. Clinical Endocrinology [<a href="https://pubmed.ncbi.nlm.nih.gov/32780518" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32780518</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng187er1.s1.3.ref27">Raharusun, Prabowo, Priambada, Sadiah, Budiarti, Cahni
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et al. (2020) Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study.</div></p></li></ul></div></ul></div></div></div><div id="appendixesappgroup1"><h2 id="_appendixesappgroup1_">Appendices</h2><div id="niceng187er1.appa"><h3>Appendix A. Review protocols</h3><div id="niceng187er1.appa.s1"><h4>A.1.1. Review question 1</h4><p id="niceng187er1.appa.tab1"><a href="/books/NBK566064/table/niceng187er1.appa.tab1/?report=objectonly" target="object" rid-ob="figobniceng187er1appatab1" class="figpopup">Table 1. Review protocol for review question 1</a></p></div><div id="niceng187er1.appa.s2"><h4>A.1.2. Review question 2</h4><p id="niceng187er1.appa.tab2"><a href="/books/NBK566064/table/niceng187er1.appa.tab2/?report=objectonly" target="object" rid-ob="figobniceng187er1appatab2" class="figpopup">Table 2. Review protocol for review question 2</a></p></div><div id="niceng187er1.appa.s3"><h4>A.1.3. Review question 3</h4><p id="niceng187er1.appa.tab3"><a href="/books/NBK566064/table/niceng187er1.appa.tab3/?report=objectonly" target="object" rid-ob="figobniceng187er1appatab3" class="figpopup">Table 3. Review protocol for review question 3</a></p></div></div><div id="niceng187er1.appb"><h3>Appendix B. Literature search strategies</h3><p>Deduplication against the previous review was used to draw out any new references, rather than date limiting in any individual source.</p><div id="niceng187er1.appb.s1"><h4>Medline ALL</h4><p>Search looked at 2002 to October 27th 2020</p><ol><li class="half_rhythm"><div>exp Vitamin D/ (59709)</div></li><li class="half_rhythm"><div>exp Vitamin D Deficiency/ (28155)</div></li><li class="half_rhythm"><div>((vitamin* adj5 D*2) or vitaminD*2).af. (99557)</div></li><li class="half_rhythm"><div>(ergocalciferol* or calciferol* or vs041h42xc or dihydrotachysterol* or dihydrotachysterin* or calcamine or 67-96-9 or r5lm3h112r or Hydroxyvitamin D*2 or 25Hydroxyvitamin D*2 or HydroxyvitaminD*2 or 25HydroxyvitaminD*2 or hydroxycalciferol* or 25hydroxycalciferol* or hydroxyergocalciferol* or 25hydroxyergocalciferol* or ercalcidiol or “25(OH)D” or 21343-40-8 or alfacalcidol*).af. (24782)</div></li><li class="half_rhythm"><div>(cholecalciferol* or colecalciferol* or calciol or 67-97-0 or 1c6v77qf41 or hydroxycholecalciferol* or hydroxycolecalciferol* or 25hydroxycholecalciferol* or 25hydroxycolecalciferol* or calcifediol* or calcidiol* or “19356-17-3” or p6yz13c99q or t0wxw8f54e or dihydroxycholecalciferol* or dihydroxycolecalciferol* or 25dihydroxycholecalciferol* or 25dihydroxycolecalciferol* or dihydroxyvitamin D*2 or 25dihydroxyvitamin* or dihydroxyvitaminD*2 or calcitriol* or 32222-06-3 or 40013-87-4 or 55721-11-4).af. (38720)</div></li><li class="half_rhythm"><div>or/1–5 (120807)</div></li><li class="half_rhythm"><div>exp coronavirus/ (39116)</div></li><li class="half_rhythm"><div>exp Coronavirus Infections/ (42273)</div></li><li class="half_rhythm"><div>((corona* or corono*) adj1 (virus* or viral* or virinae*)).ti,ab,kw,kf. (2176)</div></li><li class="half_rhythm"><div>(coronavirus* or coronovirus* or coronavirinae* or CoV or HCoV* or Betacoronavirus* or Betacoronovirus*).ti,ab,kw,kf. (49098)</div></li><li class="half_rhythm"><div>(“2019-nCoV*” or 2019nCoV* or “19-nCoV*” or 19nCoV* or nCoV2019* or “nCoV-2019*” or nCoV19* or “nCoV-19*” or “COVID-19*” or COVID19* or “COVID-2019*” or COVID2019* or “HCoV-19*” or HCoV19* or “HCoV-2019*” or HCoV2019* or “2019 novel*” or Ncov* or “n-cov” or “SARS-CoV-2*” or “SARSCoV-2*” or “SARSCoV2*” or “SARS-CoV2*” or SARSCov19* or “SARS-Cov19*” or “SARSCov-19*” or “SARS-Cov-19*” or SARSCov2019* or “SARS-Cov2019*” or “SARSCov-2019*” or “SARS-Cov-2019*” or SARS2* or “SARS-2*” or SARScoronavirus2* or “SARS-coronavirus-2*” or “SARScoronavirus 2*” or “SARS coronavirus2*” or SARScoronovirus2* or “SARS-coronovirus-2*” or “SARScoronovirus 2*” or “SARS coronovirus2*” or covid).ti,ab,kw,kf. (65326)</div></li><li class="half_rhythm"><div>(respiratory* adj2 (symptom* or disease* or illness* or condition*) adj5 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw,kf. (301)</div></li><li class="half_rhythm"><div>((“seafood market*” or “food market*”) adj10 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw,kf. (85)</div></li><li class="half_rhythm"><div>(pneumonia* adj3 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw,kf. (527)</div></li><li class="half_rhythm"><div>((outbreak* or wildlife* or pandemic* or epidemic*) adj1 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw,kf. (316)</div></li><li class="half_rhythm"><div>Middle East Respiratory Syndrome Coronavirus/ (1371)</div></li><li class="half_rhythm"><div>(“middle east respiratory syndrome*” or “middle eastern respiratory syndrome*” or MERSCoV* or “MERS-CoV*” or MERS).ti,ab,kw,kf. (5948)</div></li><li class="half_rhythm"><div>(“severe acute respiratory syndrome*” or SARS).ti,ab,kw,kf. (32888)</div></li><li class="half_rhythm"><div>(“SARS-CoV-1*” or “SARSCoV-1*” or “SARSCoV1*” or “SARS-CoV1*” or SARSCoV or “SARS-CoV” or SARS1* or “SARS-1*” or SARScoronavirus1* or “SARS-coronavirus-1*” or “SARScoronavirus 1*” or “SARS coronavirus1*” or SARScoronovirus1* or “SARS-coronovirus-1*” or “SARScoronovirus 1*” or “SARS coronovirus1*”).ti,ab,kw,kf. (23577)</div></li><li class="half_rhythm"><div>or/7–19 (95256)</div></li><li class="half_rhythm"><div>6 and 20 (290)</div></li><li class="half_rhythm"><div>21 (290)</div></li><li class="half_rhythm"><div>limit 22 to (english language and yr=“2002 -Current”) (288)</div></li><li class="half_rhythm"><div>animals/ not (humans/ and animals/) (4716381)</div></li><li class="half_rhythm"><div>23 not 24 (283)</div></li></ol></div><div id="niceng187er1.appb.s2"><h4>Embase</h4><p>2002 to October 27th 2020</p><ol><li class="half_rhythm"><div>exp vitamin D/ (144538)</div></li><li class="half_rhythm"><div>vitamin D deficiency/ (30650)</div></li><li class="half_rhythm"><div>((vitamin* adj5 D*2) or vitaminD*2).af. (152453)</div></li><li class="half_rhythm"><div>(ergocalciferol* or calciferol* or vs041h42xc or dihydrotachysterol* or dihydrotachysterin* or calcamine or 67-96-9 or r5lm3h112r or Hydroxyvitamin D*2 or 25Hydroxyvitamin D*2 or HydroxyvitaminD*2 or 25HydroxyvitaminD*2 or hydroxycalciferol* or 25hydroxycalciferol* or hydroxyergocalciferol* or 25hydroxyergocalciferol* or ercalcidiol or “25(OH)D” or 21343-40-8 or alfacalcidol*).af. (46690)</div></li><li class="half_rhythm"><div>(cholecalciferol* or colecalciferol* or calciol or 67-97-0 or 1c6v77qf41 or hydroxycholecalciferol* or hydroxycolecalciferol* or 25hydroxycholecalciferol* or 25hydroxycolecalciferol* or calcifediol* or calcidiol* or “19356-17-3” or p6yz13c99q or t0wxw8f54e or dihydroxycholecalciferol* or dihydroxycolecalciferol* or 25dihydroxycholecalciferol* or 25dihydroxycolecalciferol* or dihydroxyvitamin D*2 or 25dihydroxyvitamin* or dihydroxyvitaminD*2 or calcitriol* or 32222-06-3 or 40013-87-4 or 55721-11-4).af. (62783)</div></li><li class="half_rhythm"><div>or/1–5 (184996)</div></li><li class="half_rhythm"><div>exp Coronavirinae/ (20645)</div></li><li class="half_rhythm"><div>exp Coronavirus infection/ (22005)</div></li><li class="half_rhythm"><div>(“coronavirus disease 2019” or “severe acute respiratory syndrome coronavirus 2”).sh,dj. (59354)</div></li><li class="half_rhythm"><div>((corona* or corono*) adj1 (virus* or viral* or virinae*)).ti,ab,kw. (1675)</div></li><li class="half_rhythm"><div>(coronavirus* or coronovirus* or coronavirinae* or CoV or HCoV* or Betacoronavirus* or Betacoronovirus*).ti,ab,kw. (49400)</div></li><li class="half_rhythm"><div>(“2019-nCoV*” or 2019nCoV* or “19-nCoV*” or 19nCoV* or nCoV2019* or “nCoV-2019*” or nCoV19* or “nCoV-19*” or “COVID-19*” or COVID19* or “COVID-2019*” or COVID2019* or “HCoV-19*” or HCoV19* or “HCoV-2019*” or HCoV2019* or “2019 novel*” or Ncov* or “n-cov” or “SARS-CoV-2*” or “SARSCoV-2*” or “SARSCoV2*” or “SARS-CoV2*” or SARSCov19* or “SARS-Cov19*” or “SARSCov-19*” or “SARS-Cov-19*” or SARSCov2019* or “SARS-Cov2019*” or “SARSCov-2019*” or “SARS-Cov-2019*” or SARS2* or “SARS-2*” or SARScoronavirus2* or “SARS-coronavirus-2*” or “SARScoronavirus 2*” or “SARS coronavirus2*” or SARScoronovirus2* or “SARS-coronovirus-2*” or “SARScoronovirus 2*” or “SARS coronovirus2*” or covid).ti,ab,kw. (62449)</div></li><li class="half_rhythm"><div>(respiratory* adj2 (symptom* or disease* or illness* or condition*) adj5 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw. (372)</div></li><li class="half_rhythm"><div>((“seafood market*” or “food market*”) adj10 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw. (93)</div></li><li class="half_rhythm"><div>(pneumonia* adj3 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw. (583)</div></li><li class="half_rhythm"><div>((outbreak* or wildlife* or pandemic* or epidemic*) adj1 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)).ti,ab,kw. (146)</div></li><li class="half_rhythm"><div>Middle East respiratory syndrome/ (1633)</div></li><li class="half_rhythm"><div>(“middle east respiratory syndrome*” or “middle eastern respiratory syndrome*” or MERSCoV* or “MERS-CoV*” or MERS).ti,ab,kw. (6425)</div></li><li class="half_rhythm"><div>(“severe acute respiratory syndrome*” or SARS).ti,ab,kw. (32952)</div></li><li class="half_rhythm"><div>(“SARS-CoV-1*” or “SARSCoV-1*” or “SARSCoV1*” or “SARS-CoV1*” or SARSCoV or “SARS-CoV” or SARS1* or “SARS-1*” or SARScoronavirus1* or “SARS-coronavirus-1*” or “SARScoronavirus 1*” or “SARS coronavirus1*” or SARScoronovirus1* or “SARS-coronovirus-1*” or “SARScoronovirus 1*” or “SARS coronovirus1*”).ti,ab,kw. (22626)</div></li><li class="half_rhythm"><div>or/7–20 (99755)</div></li><li class="half_rhythm"><div>limit 21 to medline (25815)</div></li><li class="half_rhythm"><div>21 not 22 (73940)</div></li><li class="half_rhythm"><div>6 and 23 (413)</div></li><li class="half_rhythm"><div>nonhuman/ not (human/ and nonhuman/) (4724889)</div></li><li class="half_rhythm"><div>24 not 25 (398)</div></li><li class="half_rhythm"><div>limit 26 to (english language and yr=“2002 -Current”) (388)</div></li></ol></div><div id="niceng187er1.appb.s3"><h4>Cochrane Database of Systematic Reviews (CDSR) & CENTRAL</h4><p>Issue 10 of 12, 2020</p><p>ID Search</p><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>#1.</dt><dd><p class="no_top_margin">MeSH descriptor: [Vitamin D] explode all trees</p></dd></dl><dl class="bkr_refwrap"><dt>#2.</dt><dd><p class="no_top_margin">MeSH descriptor: [Vitamin D Deficiency] explode all trees</p></dd></dl><dl class="bkr_refwrap"><dt>#3.</dt><dd><p class="no_top_margin">((vitamin* near/5 D*) or vitaminD*)</p></dd></dl><dl class="bkr_refwrap"><dt>#4.</dt><dd><p class="no_top_margin">(ergocalciferol* or calciferol* or vs041h42xc or dihydrotachysterol* or dihydrotachysterin* or calcamine or “67-96-9” or “r5lm3h112r” or “Hydroxyvitamin D*” or “25Hydroxyvitamin D*” or “HydroxyvitaminD*” or “25HydroxyvitaminD*” or hydroxycalciferol* or 25hydroxycalciferol* or hydroxyergocalciferol* or 25hydroxyergocalciferol* or ercalcidiol or “25(OH)D” or “21343-40-8” or alfacalcidol*)</p></dd></dl><dl class="bkr_refwrap"><dt>#5.</dt><dd><p class="no_top_margin">(cholecalciferol* or colecalciferol* or calciol or “67-97-0” or 1c6v77qf41 or hydroxycholecalciferol* or hydroxycolecalciferol* or 25hydroxycholecalciferol* or 25hydroxycolecalciferol* or calcifediol* or calcidiol* or “19356-17-3” or p6yz13c99q or t0wxw8f54e or dihydroxycholecalciferol* or dihydroxycolecalciferol* or 25dihydroxycholecalciferol* or 25dihydroxycolecalciferol* or dihydroxyvitamin D* or 25dihydroxyvitamin* or dihydroxyvitaminD* or calcitriol* or “32222-06-3” or “40013-87-4” or “55721-11-4”)</p></dd></dl><dl class="bkr_refwrap"><dt>#6.</dt><dd><p class="no_top_margin">#1 or #2 or #3 or #4 or #5</p></dd></dl><dl class="bkr_refwrap"><dt>#7.</dt><dd><p class="no_top_margin">MeSH descriptor: [Coronavirus] explode all trees</p></dd></dl><dl class="bkr_refwrap"><dt>#8.</dt><dd><p class="no_top_margin">MeSH descriptor: [Coronavirus Infections] explode all trees</p></dd></dl><dl class="bkr_refwrap"><dt>#9.</dt><dd><p class="no_top_margin">((corona* or corono*) near/1 (virus* or viral* or virinae*)):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#10.</dt><dd><p class="no_top_margin">(coronavirus* or coronovirus* or coronavirinae* or CoV or HCoV* or Betacoronavirus* or Betacoronovirus*):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#11.</dt><dd><p class="no_top_margin">(“2019 nCoV” or 2019nCoV* or “19 nCoV” or 19nCoV* or nCoV2019* or “nCoV 2019” or nCoV19* or “nCoV 19” or “COVID 19” or COVID19* or “COVID 2019” or COVID2019* or “HCoV 19” or HCoV19* or “HCoV 2019” or HCoV2019* or “2019 novel” or Ncov* or “n cov” or “SARS CoV 2” or “SARSCoV 2” or “SARSCoV2” or “SARS CoV2” or SARSCov19* or “SARS Cov19” or “SARSCov 19” or “SARS Cov 19” or SARSCov2019* or “SARS Cov2019” or “SARSCov 2019” or “SARS Cov 2019” or SARS2* or “SARS 2” or SARScoronavirus2* or “SARS coronavirus 2” or “SARScoronavirus 2” or “SARS coronavirus2” or SARScoronovirus2* or “SARS coronovirus 2” or “SARScoronovirus 2” or “SARS coronovirus2” or covid):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#12.</dt><dd><p class="no_top_margin">(respiratory* near/2 (symptom* or disease* or illness* or condition*) near/5 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#13.</dt><dd><p class="no_top_margin">((“seafood market” or “seafood markets” or “food market” or “food markets”) near/10 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#14.</dt><dd><p class="no_top_margin">(pneumonia* near/3 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#15.</dt><dd><p class="no_top_margin">((outbreak* or wildlife* or pandemic* or epidemic*) near/1 (Wuhan* or Hubei* or China* or Chinese* or Huanan*)):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#16.</dt><dd><p class="no_top_margin">MeSH descriptor: [Middle East Respiratory Syndrome Coronavirus] explode all trees</p></dd></dl><dl class="bkr_refwrap"><dt>#17.</dt><dd><p class="no_top_margin">(“middle east respiratory syndrome” or “middle eastern respiratory syndrome” or “middle east respiratory syndromes” or “middle eastern respiratory syndromes” or MERSCoV* or “MERS CoV” or MERS):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#18.</dt><dd><p class="no_top_margin">(“severe acute respiratory syndrome” or “severe acute respiratory syndromes” or SARS):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#19.</dt><dd><p class="no_top_margin">(“SARS CoV 1” or “SARSCoV 1” or “SARSCoV1” or “SARS CoV1” or SARSCoV or SARS CoV or SARS1 or “SARS 1” or SARScoronavirus1 or “SARS coronavirus 1” or “SARScoronavirus 1” or “SARS coronavirus1” or SARScoronovirus1 or “SARS coronovirus 1” or “SARScoronovirus 1” or “SARS coronovirus1”):ti,ab,kw</p></dd></dl><dl class="bkr_refwrap"><dt>#20.</dt><dd><p class="no_top_margin">{or #7–#19}</p></dd></dl><dl class="bkr_refwrap"><dt>#21.</dt><dd><p class="no_top_margin">#6 and #20</p></dd></dl><dl class="bkr_refwrap"><dt>#22.</dt><dd><p class="no_top_margin">(clinicaltrials or trialsearch):so</p></dd></dl><dl class="bkr_refwrap"><dt>#23.</dt><dd><p class="no_top_margin">#21 not #22</p></dd></dl></dl></div><div id="niceng187er1.appb.s4"><h4>MedRxiv & BioRxiv preprints</h4><p>This database comprises a full copy of the <a href="https://connect.medrxiv.org/relate/content/181" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">medRxiv and bioRxiv Covid-19/SARS-CoV-2 collection</a>, which was downloaded via a custom feed. The EPPI database feed was run at 8am on the 23<sup>rd</sup> October 2020 before being sifted for relevance to the vitamin D topic. We did not use the native interface in MedRxiv or BioRxiv due to problems with the search functionality and data extraction options.</p><p>1 additional result was identified by searching for references from the medRxiv and bioRxiv Covid-19/SARS-CoV-2 collection that had appeared in our custom feed between 8am on the 23<sup>rd</sup> October and 10am on the 29<sup>th</sup> October 2020. This set of references have not previously been assessed by NICE for relevance to the vitamin D topic. The following terms were searched for in the title and abstract fields of these records in EPPI reviewer: vitamin; hydroxyvitamin; dihydroxyvitamin, ergocalciferol; calciferol; cholecalciferol; colecalciferol (combined with the Boolean ‘OR’).</p><p>Note that EPPI Reviewer 5 automatically truncates search terms.</p></div><div id="niceng187er1.appb.s5"><h4>World Health Organization Global research on coronavirus disease (COVID-19)</h4><p>Search conducted 29/10/2020.</p><p>tw:(“vitamin D” OR “vitamin D1” OR “vitamin D2” OR “vitamin D3” OR “vitamin D4” OR “vitamin D5” OR hydroxyvitamin OR dihydroxyvitamin OR ergocalciferol OR calciferol OR cholecalciferol OR colecalciferol)</p><p>348 results</p></div><div id="niceng187er1.appb.s6"><h4>
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<a href="http://Clinicaltrials.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Clinicaltrials.gov</a>
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</h4><p>Search conducted 29/10/2020.</p><p><b>Condition:</b> covid OR ncov OR 2019nCoV OR covid19 OR SARS OR (Severe Acute Respiratory Syndrome) OR Coronavirus OR corona OR orthocoronavirinae OR MERS OR (middle respiratory syndrome)</p><p><b>Other terms:</b> (Vitamin (d OR d1 OR d2 OR d3 OR d4 OR d5)) OR hydroxyvitamin OR dihydroxyvitamin OR ergocalciferol OR calciferol OR cholecalciferol OR colecalciferol</p></div></div><div id="niceng187er1.appc"><h3>Appendix C. Effectiveness & association evidence study selection</h3><div id="niceng187er1.appc.s1"><h4>C.1.1. Review question 1</h4><p id="niceng187er1.appc.fig1"><a href="/books/NBK566064/figure/niceng187er1.appc.fig1/?report=objectonly" target="object" rid-ob="figobniceng187er1appcfig1" class="figpopup">Figure 1. Review question 1</a></p></div><div id="niceng187er1.appc.s2"><h4>C.1.2. Review question 2</h4><p id="niceng187er1.appc.fig2"><a href="/books/NBK566064/figure/niceng187er1.appc.fig2/?report=objectonly" target="object" rid-ob="figobniceng187er1appcfig2" class="figpopup">Figure 2. Review question 2</a></p></div><div id="niceng187er1.appc.s3"><h4>C.1.3. Review question 3</h4><p id="niceng187er1.appc.fig3"><a href="/books/NBK566064/figure/niceng187er1.appc.fig3/?report=objectonly" target="object" rid-ob="figobniceng187er1appcfig3" class="figpopup">Figure 3. Review question 3</a></p></div></div><div id="niceng187er1.appd"><h3>Appendix D. Effectiveness & association evidence</h3><div id="niceng187er1.appd.s1"><h4>D.1. Effectiveness evidence</h4><div id="niceng187er1.appd.s1.1"><h5>D.1.1. Vitamin D as treatment</h5><p id="niceng187er1.appd.et1"><a href="/books/NBK566064/bin/niceng187er1-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.1.1.1.
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Entrenas Castillo 2020
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</a><span class="small"> (PDF, 254K)</span></p></div></div><div id="niceng187er1.appd.s2"><h4>D.2. Association evidence</h4><p id="niceng187er1.appd.et2"><a href="/books/NBK566064/bin/niceng187er1-appd-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.1.
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Annweiler 2020
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</a><span class="small"> (PDF, 238K)</span></p><p id="niceng187er1.appd.et3"><a href="/books/NBK566064/bin/niceng187er1-appd-et3.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.2. Annweiler 2020a</a><span class="small"> (PDF, 261K)</span></p><p id="niceng187er1.appd.et4"><a href="/books/NBK566064/bin/niceng187er1-appd-et4.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.3.
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Hastie 2020
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</a><span class="small"> (PDF, 259K)</span></p><p id="niceng187er1.appd.et5"><a href="/books/NBK566064/bin/niceng187er1-appd-et5.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.4.
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Hernandez 2020
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</a><span class="small"> (PDF, 312K)</span></p><p id="niceng187er1.appd.et6"><a href="/books/NBK566064/bin/niceng187er1-appd-et6.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.5.
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Karahan 2020
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</a><span class="small"> (PDF, 254K)</span></p><p id="niceng187er1.appd.et7"><a href="/books/NBK566064/bin/niceng187er1-appd-et7.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.6.
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Kaufman 2020
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</a><span class="small"> (PDF, 201K)</span></p><p id="niceng187er1.appd.et8"><a href="/books/NBK566064/bin/niceng187er1-appd-et8.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.7.
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Macaya 2020
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</a><span class="small"> (PDF, 247K)</span></p><p id="niceng187er1.appd.et9"><a href="/books/NBK566064/bin/niceng187er1-appd-et9.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.8.
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Meltzer 2020
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</a><span class="small"> (PDF, 323K)</span></p><p id="niceng187er1.appd.et10"><a href="/books/NBK566064/bin/niceng187er1-appd-et10.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.9.
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Merzon 2020
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</a><span class="small"> (PDF, 206K)</span></p><p id="niceng187er1.appd.et11"><a href="/books/NBK566064/bin/niceng187er1-appd-et11.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.10.
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Radujkovic 2020
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</a><span class="small"> (PDF, 280K)</span></p><p id="niceng187er1.appd.et12"><a href="/books/NBK566064/bin/niceng187er1-appd-et12.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.11.
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Raisi-Estabragh 2020
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</a><span class="small"> (PDF, 221K)</span></p><p id="niceng187er1.appd.et13"><a href="/books/NBK566064/bin/niceng187er1-appd-et13.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.2.1.12.
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Ye 2020
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</a><span class="small"> (PDF, 243K)</span></p></div></div><div id="niceng187er1.appe"><h3>Appendix E. GRADE tables</h3><div id="niceng187er1.appe.s1"><h4>E.1.1. Effectiveness of vitamin D as a COVID-19 treatment</h4><div id="niceng187er1.appe.s1.1"><h5>E.1.1.1. Effectiveness of vitamin D supplement as treatment for COVID-19</h5><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1appetab1"><a href="/books/NBK566064/table/niceng187er1.appe.tab1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1appetab1" rid-ob="figobniceng187er1appetab1"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.appe.tab1/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.appe.tab1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.appe.tab1"><a href="/books/NBK566064/table/niceng187er1.appe.tab1/?report=objectonly" target="object" rid-ob="figobniceng187er1appetab1">Table</a></h4><p class="float-caption no_bottom_margin">OR 0.02 (0.002 to 0.17)</p></div></div></div></div><div id="niceng187er1.appe.s2"><h4>E.1.2. Effectiveness of vitamin as a COVID-19 preventative measure</h4><p>No evidence found</p></div><div id="niceng187er1.appe.s3"><h4>E.1.3. Association between vitamin D status and COVID-19 outcomes</h4><div id="niceng187er1.appe.s3.1"><h5>E.1.3.1. Association between vitamin D status and COVID-19 cases</h5><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1appetab2"><a href="/books/NBK566064/table/niceng187er1.appe.tab2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1appetab2" rid-ob="figobniceng187er1appetab2"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.appe.tab2/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.appe.tab2/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.appe.tab2"><a href="/books/NBK566064/table/niceng187er1.appe.tab2/?report=objectonly" target="object" rid-ob="figobniceng187er1appetab2">Table</a></h4><p class="float-caption no_bottom_margin">Case control Cases n=449</p></div></div></div><div id="niceng187er1.appe.s3.2"><h5>E.1.3.2. Association between vitamin D status and severity of COVID-19</h5><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1appetab3"><a href="/books/NBK566064/table/niceng187er1.appe.tab3/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1appetab3" rid-ob="figobniceng187er1appetab3"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.appe.tab3/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.appe.tab3/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.appe.tab3"><a href="/books/NBK566064/table/niceng187er1.appe.tab3/?report=objectonly" target="object" rid-ob="figobniceng187er1appetab3">Table</a></h4><p class="float-caption no_bottom_margin">Vitamin D status definition: Vitamin D level (nmol/L) Severity definition: composite severity endpoint (admission to the intensive care unit (ICU), requirement for mechanical ventilation, or in-hospital mortality)</p></div></div></div></div></div><div id="niceng187er1.appf"><h3>Appendix F. Ongoing studies (<a href="http://clinicaltrials.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">clinicaltrials.gov</a>)</h3><p>
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<b>Search date: 29/10/2020</b>
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</p><div id="niceng187er1.appf.s1"><h4>F.1.1. Prevention</h4><div id="niceng187er1.appf.s1.1"><h5>F.1.1.1. As monotherapy</h5><p>Double-blind randomized design comparing 1000 I.U. vitamin D versus matched placebo in healthy young adults. (Reducing Asymptomatic Infection With Vitamin D in Coronavirus Disease).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04476680" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04476680</a>
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</p><p>Parallel-group, placebo-controlled trial of vitamin D3 supplementation for the Prevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthcare Teams (PROTECT).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04483635" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04483635</a>
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</p><p>A multicenter randomized double-blinded placebo-controlled clinical trial with parallel groups design to investigate the Preventive and Therapeutic Effects of Oral 25-hydroxyvitamin D3 on Coronavirus (COVID-19) in Adults.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04386850" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04386850</a>
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</p><p>Blinded randomized clinical trial on the efficacy of Vitamin D Supplementation to Prevent the Risk of Acquiring or Evolving Into the Severe Form of COVID-19 in Healthcare Workers Caring for Patients With the Disease.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04535791" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04535791</a>
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</p><p>Phase 3 Randomised Controlled Trial of Vitamin D Supplementation to Reduce Risk and Severity of COVID-19 and Other Acute Respiratory Infections in the UK Population</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04579640" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04579640</a>
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</p></div><div id="niceng187er1.appf.s1.2"><h5>F.1.1.2. As combination therapy</h5><p>Open-label RCT of vitamin D3 2000 IU (50 μg) plus 30 mg of zinc gluconate per day for 2 months versus usual care in adults >60 years who are ‘institutionalised’ but asymptomatic. Incidence of COVID-19 infection is a secondary outcome (Seguy D. Impact of Zinc and Vitamin D3 Supplementation on the Survival of Aged Patients Infected With COVID-19 (ZnD3-CoVici)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04351490" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04351490</a>
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</p><p>Single group open-label study of a combination of hydroxychloroquine, vitamins C and D (form not specified), and zinc as prophylaxis in healthy healthcare workers who are at risk of COVID-19 (Haza S. A Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection (HELPCOVID-19)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/record/NCT04335084" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/record/NCT04335084</a>
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</p><p>Open label RCT investigating interventions to prevent progression of COVID-19. Interventions include hydroxychloroquine, azithromycin, zinc, vitamin D, vitamin B12 with or without vitamin C. (International ALLIANCE Study of Therapies to Prevent Progression of COVID-19)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04395768" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04395768</a>
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</p><p>A Randomized, Double-Blind, Placebo-Controlled Phase IIa Study of Hydroxychloroquine, Vitamin C, Vitamin D, and Zinc for the Prevention of COVID-19 Infection on medical workers who at elevated risk of COVID-19 due to exposure to positive patients in the Emergency Department or Intensive Care Unit.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04335084" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04335084</a>
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</p><p>A prospective, double-blind, randomized, placebo-controlled study in two distinct cohorts to evaluate the efficacy and safety of hydroxychloroquine (with vitamin D) in the prevention of COVID-19 infection.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04372017" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04372017</a>
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</p></div></div><div id="niceng187er1.appf.s2"><h4>F.1.2. Treatment</h4><div id="niceng187er1.appf.s2.1"><h5>F.1.2.1. As monotherapy</h5><p>Randomised controlled trial of a single oral dose of 25,000 IU (625 μg) vitamin D (form not specified) versus usual care in patients who are infected with SARS-CoV-2 but do not have severe symptoms (Castillo MJ. Vitamin D on Prevention and Treatment of COVID-19 (COVITD-19)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04334005" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04334005</a>
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</p><p>RCT comparing single doses of vitamin D3, 50,000 IU to 200,000 IU (1250 Vs 5000 μg) in people with COVID-19 pneumonia >75 years of age, or >70 with low oxygen saturations (Annweiler C. COvid-19 and Vitamin D Supplementation: a Multicenter Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-risk COVID-19 Patients (CoVitTrial)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/record/NCT04344041" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/record/NCT04344041</a>
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</p><p>RCT comparing vitamin D3 (500,000 IU single dose) to placebo in adults admitted to hospital with COVID-19. Primary outcomes are respiratory SOFA at one week and need for high dose oxygen or mechanical ventilation at 30 days. (Cholecalciferol to Improve the Outcomes of COVID-19 Patients (CARED))</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04411446" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04411446</a>
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</p><p>Single group open-label study of vitamin D supplementation (form not specified) in adults with COVID-19 and vitamin D deficiency (threshold for deficiency not defined). Participants to receive 2 weeks of vitamin D supplementation (10–15,000 IU based on age), with a further 3 weeks treatment if vitamin D levels remain low. Outcomes include 25(OH)D level and COVID-19 symptoms. (Vitamin D Testing and Treatment for COVID 19)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04407286" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04407286</a>
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</p><p>Randomised controlled trial comparing 2 doses of vitamin D3 (50,000 IU twice/once weekly and 1,000 IU daily) with low dose vitamin D3 in adults with COVID-19. Primary outcome: COVID-19 symptom recovery at 3 weeks. (Vitamin D and COVID-19 Management)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04385940" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04385940</a>
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</p><p>A Cluster-Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Vitamin D3 Supplementation to Reduce Disease Severity in Persons With Newly Diagnosed COVID-19 Infection and to Prevent Infection in Household Members.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04536298" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04536298</a>
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</p><p>Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04411446" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04411446</a>
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</p><p>Open label randomised parallel study on the Prevention and Treatment With Calcifediol of COVID-19 Coronavirus-induced Acute Respiratory Syndrome (SARS).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04366908" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04366908</a>
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</p><p>A Multicentre Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-risk COVID-19 Patients (CoVitTrial).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04344041" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04344041</a>
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</p><p>Vitamin D Supplementation in Patients With COVID-19: A Randomized, Double-blind, Placebo-controlled Trial.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04449718" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04449718</a>
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</p><p>Randomised parallel trial on the Effect of Vitamin D Administration on Prevention and Treatment of Mild Forms of Suspected Covid-19.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04334005" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04334005</a>
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</p><p>Randomised Parallel Trial on The Role of Vitamin D in Mitigating COVID-19 Infection Severity: Focusing on Reducing Health Disparities in South Carolina (VitD-COVID19).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04482673" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04482673</a>
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</p><p>Randomised Parallel Trial To determine the efficacy of high dose Vitamin D (an over-the-counter nutritional supplement) in preventing immune-related complications in outpatients with confirmed SARS-CoV-2 infection.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04489628" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04489628</a>
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</p><p>An open label treatment study for people with COVID 19 and low levels of vitamin D.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04407286" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04407286</a>
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</p><p>Randomised Parallel Trial on the Effect of Vitamin D on Morbidity and Mortality of the COVID-19 (COVID-VIT-D).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04552951" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04552951</a>
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</p><p>High Dose Vitamin-D Substitution in Patients With COVID-19: a Randomized Controlled, Multi Centre Study (VitCov).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04525820" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04525820</a>
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</p><p>A double blind, randomized, controlled three weeks clinical trial on the efficacy of vitamin D (daily low dose versus weekly high dose) in COVID-19 patients in order to determine the relationship between baseline vitamin D deficiency and clinical characteristics and to asses patients’ response to vitamin D supplementation in week three and determine its association with disease progression and recovery.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04385940" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04385940</a>
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</p><p>Efficacy of Vitamin D Treatment in Paediatric Patients Hospitalized by COVID-19: Open Controlled Clinical Trial.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04502667" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04502667</a>
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</p><p>Randomised Double Blind Controlled Study on Short Term, High Dose Vitamin D Supplementation for COVID-19 (SHADE).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04459247" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04459247</a>
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</p></div><div id="niceng187er1.appf.s2.2"><h5>F.1.2.2. As combination therapy</h5><p>Single group open-label study of a combination of hydroxychloroquine, vitamins C and D (form not specified), and zinc plus azithromycin as treatment for COVID-19 (Haza S. A Study of Quintuple Therapy to Treat COVID-19 Infection (HAZDpaC)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04334512" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04334512</a>
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</p><p>Open-label RCT of vitamin D (form not specified; 50,000 IU once weekly for 2/52) added to aspirin 81 mg daily for 2/52. Investigating whether early treatment with aspirin and vitamin D in COVID-19 can mitigate COVID-19-associated coagulopathy and reduce hospitalization rates. (The LEAD COVID-19 Trial: Low-risk, Early Aspirin and Vitamin D to Reduce COVID-19 Hospitalizations)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04363840" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04363840</a>
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</p><p>Open label randomised parallel study on the Impact of Zinc and Vitamin D3 Supplementation on the Survival of Institutionalized Aged Patients Infected With COVID-19.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04351490" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04351490</a>
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</p><p>Multi-center, prospective, randomized controlled trial is to investigate low-risk, early treatment with aspirin and vitamin D in COVID-19 can mitigate the prothrombotic state and reduce hospitalization rates. (The LEAD COVID-19 Trial).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04363840" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04363840</a>
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</p><p>A Randomized, Double-Blind, Placebo-Controlled Phase IIa Study of Quintuple Therapy (Hydroxychloroquine, Azithromycin, Vitamin C, Vitamin D, and Zinc) to Treat COVID-19 Infection.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04334512" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04334512</a>
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</p><p>A Phase II Double-Blind Randomized Placebo-Controlled Trial of Combination Therapy (Ivermectin, Doxycycline Hcl, Zinc, Vitamin D3, Vitamin C) to Treat COVID-19 Infection.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04482686" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04482686</a>
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</p><p>Proof-of-concept Open-label Randomized Dose-response Comparison Study of Famotidine Plus Vitamins C and D3 for Adults With Probable COVID-19.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04565392" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04565392</a>
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</p><p>Randomized Double-Blind Placebo-Controlled Proof-of-Concept Trial of a Plant Polyphenol (with Vitamin D3) for the Outpatient Treatment of Mild Coronavirus Disease (COVID-19).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04400890" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04400890</a>
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</p><p>Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, Vitamin D, Vitamin B12 With or Without Vitamin C, a Multi-centre, International, Randomized Trial: The International ALLIANCE Study.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04395768" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04395768</a>
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</p><p>A Non-Randomised Pilot Study for COVID-19 Outpatient Treatment With the Combination of Ivermectin-azithromycin-cholecalciferol.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04399746" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04399746</a>
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</p></div></div><div id="niceng187er1.appf.s3"><h4>F.1.3. Association between vitamin D status and COVID-19</h4><p>Case-control study investigating whether serum 25(OH)D level correlates to COVID-19 disease severity in people not treated in critical care. (Do Vitamin D Levels Really Correlated With Disease Severity in COVID-19 Patients? (COVIDVIT))</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04394390" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04394390</a>
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</p><p>Case-series investigating differences in vitamin D blood levels between COVID-19 patients with different degrees of disease severity (mild-severe disease compared with patients requiring critical care). (VITACOV: Vitamin D Polymorphisms and Severity of COVID-19 Infection)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04370808" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04370808</a>
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</p><p>Case-control study investigating serum zinc, vitamin D and vitamin B12 levels in pregnant women with COVID-19. (Evaluation of the Relationship Between Zinc Vitamin D and b12 Levels in the Covid-19 Positive Pregnant Women)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04407572" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04407572</a>
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</p><p>Case-control study investigating whether vitamin D levels affect outcomes in COVID-19 infection and whether vitamin D deficiency is associated with increased risk. (Investigating the Role of Vitamin D in the Morbidity of COVID-19 Patients)</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04386044" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04386044</a>
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</p><p>Prospective cohort study investigating the association between vitamin D deficiency and worse outcomes in people admitted to hospital for COVID-19. (Increased Risk of Severe Coronavirus Disease 2019 in Patients With Vitamin D Deficiency (COVIT-D))</p><p>
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<a href="https://clinicaltrials.gov/ct2/show/NCT04403932" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://clinicaltrials.gov/ct2/show/NCT04403932</a>
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</p><p>Retrospective Pilot Study of Vitamin D Status and Immune-inflammatory Status in Different UK Populations With COVID-19 Infection</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04519034" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04519034</a>
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</p><p>Prognostic Factors and Outcomes of COVID-19 Cases in Ethiopia: Multi-Site Cohort Study. To determine the epidemiological and clinical features of COVID-19 cases, immunological and virological courses, interaction with nutritional status, and response to treatment for COVID-19 patients admitted to treatment centers in Ethiopia.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04584424" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04584424</a>
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</p><p>Observational study to investigating the Role of Vitamin D in the Morbidity of COVID-19 Patients.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04386044" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04386044</a>
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</p><p>An observational study on Vitamin D-related Polymorphisms and Vitamin D Levels as Risk Biomarkers of COVID-19 Infection Severity. (VITACOV).</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04370808" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04370808</a>
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</p><p>Prospective Cohort Study to Determine the Association Between Vitamin D Deficiency and Severity of the Disease in Patients With Coronavirus Disease.</p><p>
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<a href="https://ClinicalTrials.gov/show/NCT04403932" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04403932</a>
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</p><p>A Case-Control Study on N-terminal Pro B-type Natriuretic Peptide and Vitamin D Levels as Prognostic Markers in COVID-19 Pneumonia.</p><p>
|
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<a href="https://ClinicalTrials.gov/show/NCT04487951" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04487951</a>
|
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</p><p>A Case-Control Study to investigate Whether Vitamin D Levels Really Correlated With Disease Severity in COVID-19 Patients. (COVIDVIT)</p><p>
|
|
<a href="https://ClinicalTrials.gov/show/NCT04394390" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04394390</a>
|
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</p><p>Retrospective observational unicentric study in nursing-home residents with COVID-19. Health status monitoring data available until May 15, 2020. For all participants, gender, age, disability, history and comorbidities, treatments, date of last vitamin D3 supplementation, results of last blood test, date of suspicion / diagnosis of COVID-19, COVID-19 OSCI score, and eventual hospitalization or death (surveillance data available until May 15, 2020) are collected.</p><p>
|
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<a href="https://ClinicalTrials.gov/show/NCT04435119" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04435119</a>
|
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</p><p>A case=Control Study of the Relationship Between Zinc Vitamin D and b12 Levels in the Covid-19 Positive Pregnant Women.</p><p>
|
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<a href="https://ClinicalTrials.gov/show/NCT04407572" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://ClinicalTrials.gov/show/NCT04407572</a>
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</p></div></div><div id="niceng187er1.appg"><h3>Appendix G. Excluded studies</h3><div id="niceng187er1.appg.s1"><h4>G.1.1. Treatment</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1appgtab1"><a href="/books/NBK566064/table/niceng187er1.appg.tab1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1appgtab1" rid-ob="figobniceng187er1appgtab1"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.appg.tab1/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.appg.tab1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.appg.tab1"><a href="/books/NBK566064/table/niceng187er1.appg.tab1/?report=objectonly" target="object" rid-ob="figobniceng187er1appgtab1">Table</a></h4><p class="float-caption no_bottom_margin">- Not a peer-reviewed publication <i>A review published by CEBM posted as a webpage and not peer-reviewed</i>.</p></div></div></div><div id="niceng187er1.appg.s2"><h4>G.1.2. Prevention</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1appgtab2"><a href="/books/NBK566064/table/niceng187er1.appg.tab2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1appgtab2" rid-ob="figobniceng187er1appgtab2"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.appg.tab2/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.appg.tab2/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.appg.tab2"><a href="/books/NBK566064/table/niceng187er1.appg.tab2/?report=objectonly" target="object" rid-ob="figobniceng187er1appgtab2">Table</a></h4></div></div></div><div id="niceng187er1.appg.s3"><h4>G.1.3. Association</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng187er1appgtab3"><a href="/books/NBK566064/table/niceng187er1.appg.tab3/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figniceng187er1appgtab3" rid-ob="figobniceng187er1appgtab3"><img class="small-thumb" src="/books/NBK566064/table/niceng187er1.appg.tab3/?report=thumb" src-large="/books/NBK566064/table/niceng187er1.appg.tab3/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="niceng187er1.appg.tab3"><a href="/books/NBK566064/table/niceng187er1.appg.tab3/?report=objectonly" target="object" rid-ob="figobniceng187er1appgtab3">Table</a></h4><p class="float-caption no_bottom_margin">- Study does not contain any relevant predictive values <i>Unclear what had been adjusted in the meta-analysis</i>.</p></div></div></div></div></div></div><div class="fm-sec"><div><p>Evidence reviews underpinning recommendations 1.1 to 1.3 and research recommendations in the NICE guideline</p><p>These evidence reviews were developed by Centre for Guidelines Methods and Economics Team</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2020.</div><div class="small"><span class="label">Bookshelf ID: NBK566064</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/33378142" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">33378142</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobniceng187er1tab1"><div id="niceng187er1.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">PICO table for review question 1</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Field</th><th id="hd_h_niceng187er1.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Content</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Population</b>
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</td><td headers="hd_h_niceng187er1.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Inclusion: Adults, young people and children with confirmed COVID-19.</p>
|
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<p>Notes:
|
|
<ul><li class="half_rhythm"><div>Other coronavirus such as SARS CoV1 (symptomatic) and MERS will be included</div></li><li class="half_rhythm"><div>People with confirmed COVID-19 who are co-infected with other respiratory viruses will be included</div></li><li class="half_rhythm"><div>Subgroups will be explored
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Gender</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Comorbidities</div></li><li class="half_rhythm"><div>BMI</div></li><li class="half_rhythm"><div>Use of immune suppressing treatments</div></li><li class="half_rhythm"><div>Socioeconomic status</div></li><li class="half_rhythm"><div>Baseline vitamin D status</div></li><li class="half_rhythm"><div>COVID-19 infection severity at point of supplementation</div></li><li class="half_rhythm"><div>Other supplement use</div></li><li class="half_rhythm"><div>Timing of vitamin D measurements (for example, historical, on entry to hospital / ICU)</div></li><li class="half_rhythm"><div>Shielding status</div></li><li class="half_rhythm"><div>Living in care homes</div></li></ul></div></li></ul>
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Exclusion: Adults, young people and children with other respiratory infections unrelated to coronavirus</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Intervention</b>
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</td><td headers="hd_h_niceng187er1.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Vitamin D supplementation (all dosages, formulations and routes of administration)</p>
|
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<p>Note: Vitamin D supplementation as an adjunctive treatment will be included if other treatments are balanced out in the control arm</p>
|
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</td></tr><tr><td headers="hd_h_niceng187er1.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Comparator</b>
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</td><td headers="hd_h_niceng187er1.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Placebo or standard care or no treatment</p>
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<p>Note: for vitamin D supplementation as an adjunctive treatment, the comparator will be the index treatment(s). For example: Vitamin D + Treatment X versus Treatment X</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Outcomes</b>
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</td><td headers="hd_h_niceng187er1.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Primary outcomes:</b>
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<ul><li class="half_rhythm"><div>Mortality (including all-cause mortality and COVID-19-related mortality)</div></li><li class="half_rhythm"><div>Intensive care unit admission</div></li></ul>
|
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<b>Secondary outcomes:</b>
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|
<ul><li class="half_rhythm"><div>Hospitalisation</div></li><li class="half_rhythm"><div>Use of ventilation (including non-invasive and invasive)</div></li><li class="half_rhythm"><div>Infection cure rates (laboratory/virologically or radiographically confirmed)</div></li><li class="half_rhythm"><div>Time to clinical cure</div></li><li class="half_rhythm"><div>Complications (primary or secondary to COVID-19)</div></li><li class="half_rhythm"><div>Reduction in symptoms and/or symptom severity</div></li><li class="half_rhythm"><div>Adverse effects and safety</div></li><li class="half_rhythm"><div>Tolerability</div></li><li class="half_rhythm"><div>Long COVID</div></li></ul></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1tab2"><div id="niceng187er1.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of studies included in the evidence review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng187er1.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng187er1.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng187er1.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analysis</th><th id="hd_h_niceng187er1.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<a class="bibr" href="#niceng187er1.s1.3.ref1" rid="niceng187er1.s1.3.ref1">Entrenas Castillo 2020</a>
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</p>
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<p>RCT</p>
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<p>Spain</p>
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</td><td headers="hd_h_niceng187er1.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>N=76 admitted with confirmed COVID-19 randomised in a 2:1 ratio into intervention and comparator arms.</p>
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<p>n=50 in intervention arm, received calcifediol treatment plus standard care</p>
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<p>n=26 received standard care only</p>
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</td><td headers="hd_h_niceng187er1.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Calcifediol (0.532 mg) on admission, then 0.266 mg on days 3 and 7, then weekly until discharge.</td><td headers="hd_h_niceng187er1.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Univariate and multivariable logistic regressions were used to estimate the probability of admission to intensive care unit (ICU). Mortality was reported as number of event counts.</td><td headers="hd_h_niceng187er1.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>ICU admission</p>
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<p>COVID-19 mortality</p>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1tab3"><div id="niceng187er1.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">PICO table for review question 2</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.tab3_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Field</th><th id="hd_h_niceng187er1.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Content</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Population</b>
|
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</td><td headers="hd_h_niceng187er1.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Inclusion: Adults, young people and children who are not infected with SARS CoV2 (or SAR CoV1 and MERS).</p>
|
|
<p>Notes: Studies on specific sub-populations such as those identified as ‘vulnerable’, ‘extremely vulnerable’ or other comorbidities will be included.
|
|
<ul><li class="half_rhythm"><div>Subgroups will be explored
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Gender</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Comorbidities</div></li><li class="half_rhythm"><div>BMI</div></li><li class="half_rhythm"><div>Use of immune suppressing treatments</div></li><li class="half_rhythm"><div>Socioeconomic status</div></li><li class="half_rhythm"><div>Baseline vitamin D status</div></li><li class="half_rhythm"><div>COVID-19 infection severity at point of supplementation</div></li><li class="half_rhythm"><div>Other supplement use</div></li><li class="half_rhythm"><div>Timing of vitamin D measurements (for example, historical, on entry to hospital / ICU)</div></li><li class="half_rhythm"><div>Shielding status</div></li><li class="half_rhythm"><div>Living in care homes</div></li></ul></div></li></ul>
|
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Exclusion: Adults, young people and children who already have contracted SARS CoV2 at the point of study entry.</p>
|
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</td></tr><tr><td headers="hd_h_niceng187er1.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Intervention</b>
|
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</td><td headers="hd_h_niceng187er1.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Vitamin D supplementation (all dosages, formulations and routes of administration)</p>
|
|
<p>Note: Vitamin D supplementation as an adjunctive treatment will be included if other treatments are balanced out in the control arm</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Comparator</b>
|
|
</td><td headers="hd_h_niceng187er1.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Placebo or standard care or no treatment</p>
|
|
<p>Note: for vitamin D supplementation as an adjunctive treatment, the comparator will be the index treatment(s). For example: Vitamin D + Treatment X versus Treatment X</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Outcomes</b>
|
|
</td><td headers="hd_h_niceng187er1.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Primary outcomes:</b>
|
|
<ul><li class="half_rhythm"><div>Mortality (including all-cause mortality and COVID-19-related mortality)</div></li><li class="half_rhythm"><div>Intensive care unit admission</div></li></ul>
|
|
<b>Secondary outcomes:</b>
|
|
<ul><li class="half_rhythm"><div>Hospitalisation</div></li><li class="half_rhythm"><div>Use of ventilation (including non-invasive and invasive)</div></li><li class="half_rhythm"><div>Infection cure rates (laboratory/virologically or radiographically confirmed)</div></li><li class="half_rhythm"><div>Time to clinical cure</div></li><li class="half_rhythm"><div>Complications (primary or secondary to COVID-19)</div></li><li class="half_rhythm"><div>Reduction in symptoms and/or symptom severity</div></li><li class="half_rhythm"><div>Adverse effects and safety</div></li><li class="half_rhythm"><div>Tolerability</div></li><li class="half_rhythm"><div>Long COVID</div></li></ul></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1tab4"><div id="niceng187er1.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">protocol summary for review question 3</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.tab4_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Field</th><th id="hd_h_niceng187er1.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Content</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Population</b>
|
|
</td><td headers="hd_h_niceng187er1.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Inclusion: Adults, young people and children with confirmed COVID-19.</p>
|
|
<p>Note: Other coronavirus such as SARS CoV1 (symptomatic) and MERS will be included as indirect evidence</p>
|
|
<p>Exclusion: Adults, young people and children with other respiratory infections unrelated to coronavirus.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Dependent variables</b>
|
|
</td><td headers="hd_h_niceng187er1.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Vitamin D status (as measured by serum/plasma 25-hydroxyvitamin D [25(OH)D concentration]).</p>
|
|
<p>Deficiency is defined as serum 25(OH)D concentration <25nmol/L</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Independent variables, confounders</b>
|
|
</td><td headers="hd_h_niceng187er1.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Gender</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Comorbidities</div></li><li class="half_rhythm"><div>Body mass index</div></li><li class="half_rhythm"><div>Use of immune suppressing treatments</div></li><li class="half_rhythm"><div>Socioeconomic status</div></li><li class="half_rhythm"><div>Baseline vitamin D status</div></li><li class="half_rhythm"><div>COVID-19 infection severity at point of supplementation</div></li><li class="half_rhythm"><div>Other supplement use</div></li><li class="half_rhythm"><div>Timing of vitamin D measurements (for example, historical, on entry to hospital / intensive care unit [ICU])</div></li><li class="half_rhythm"><div>Shielding status</div></li><li class="half_rhythm"><div>Living in care homes</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<b>Outcomes</b>
|
|
</td><td headers="hd_h_niceng187er1.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Incidence of COVID-19 (laboratory/virologically confirmed)</div></li><li class="half_rhythm"><div>COVID-19 rate (laboratory/virologically confirmed)</div></li><li class="half_rhythm"><div>Severity of confirmed COVID-19 (for example, but not limited to, Centers for Disease Control and Prevention definition, World Health Organization definition, proxy such as hospitalisation, ventilation, ICU admission, and others)</div></li><li class="half_rhythm"><div>Poor outcomes (for example, mortality, complications, morbidities post infection, long COVID)</div></li></ul></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1tab5"><div id="niceng187er1.tab5" class="table"><h3><span class="label">Table 5</span><span class="title">Summary of studies included in the evidence review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.tab5_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><th id="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analysis</th><th id="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D status</th><th id="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dependent variable/confounders</th><th id="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref2" rid="niceng187er1.s1.3.ref2">Annweiler 2020</a>
|
|
</p>
|
|
<p>Retrospective quasi-experimental study</p>
|
|
<p>France</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>N=66</p>
|
|
<p>Nursing home residents diagnosed with COVID-19</p>
|
|
<p>Residents received chronic vitamin D supplementation with regular maintenance boluses (single oral dose of 80,000 IU vitamin D3 every 2 to 3 months). When residents last received supplementation dictated which group they were in:</p>
|
|
<p>n=57 received vitamin D bolus within 1 month of or a week after COVID-19 diagnosis</p>
|
|
<p>n=9 did not receive vitamin D bolus</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Associations between predictor variables, such as vitamin D3 supplements, and the likelihood of COVID-19 mortality at a specific time.</p>
|
|
<p>Comparing time to death between intervention and comparator groups.</p>
|
|
<p>Associations between bolus vitamin D3 supplements and World Health Organization Ordinal Scale for Clinical Improvement (OSCI) score, taking into account factors that may affect the result.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Determined by whether the participant had received the vitamin D bolus or not</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>COVID-19 confirmed with RT-PCR</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Sex</div></li><li class="half_rhythm"><div>Use of treatments</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>COVID-19 mortality</p>
|
|
<p>World Health Organization Ordinal Scale for Clinical Improvement (OSCI) score for COVID-19 in acute phase</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Annweiler 2020a</p>
|
|
<p>Retrospective cohort study</p>
|
|
<p>France</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=77 admitted to hospital with COVID-19</p>
|
|
<p>n=29 received vitamin D bolus over the preceding year</p>
|
|
<p>n=16 received a vitamin D supplement after COVID-19 diagnosis</p>
|
|
<p>n=32 received no vitamin D supplement</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Comparisons between groups for the reported outcomes.</p>
|
|
<p>The association between each group and 14-day mortality at a specific time, adjusting for confounders.</p>
|
|
<p>Comparison of survival between the groups.</p>
|
|
<p>Association between vitamin D status and severe COVID-19, adjusted for confounding variables.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Determined by whether the participant had received the vitamin D bolus or not</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>COVID-19 confirmed with RT-PCR</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Sex</div></li><li class="half_rhythm"><div>Use of treatments</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>14-day COVID-19 mortality</p>
|
|
<p>OSCI score for COVID-19 in acute phase</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>
|
|
</p>
|
|
<p>Retrospective cohort study</p>
|
|
<p>UK</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N = 348,598</p>
|
|
<p>n=348,139 no COVID</p>
|
|
<p>n=449 COVID-positive</p>
|
|
<p>Participants in the UK Biobank study with complete data</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Association between vitamin D and SARS-CoV-2 infection explored using multivariable logistic regression adjusted for confounding variables.</p>
|
|
<p>Interaction between vitamin D and ethnicity and its association with SARS-CoV-2 infection was explored with multivariable analysis.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Measurements taken when participants were first recruited between 2006 to 2010</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Dependent variable: SARS-CoV-2 infection as recorded by Public Health England.</div></li></ul>
|
|
Confounders:
|
|
<ul><li class="half_rhythm"><div>sex</div></li><li class="half_rhythm"><div>month of assessment</div></li><li class="half_rhythm"><div>Townsend deprivation quintile</div></li><li class="half_rhythm"><div>household income</div></li><li class="half_rhythm"><div>self-reported health rating</div></li><li class="half_rhythm"><div>smoking status</div></li><li class="half_rhythm"><div>body mass index (BMI) quintile</div></li><li class="half_rhythm"><div>ethnicity</div></li><li class="half_rhythm"><div>age at assessment</div></li><li class="half_rhythm"><div>diabetes</div></li><li class="half_rhythm"><div>systolic blood pressure</div></li><li class="half_rhythm"><div>diastolic blood pressure</div></li><li class="half_rhythm"><div>long-standing illness, disability or infirmity</div></li></ul></td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SARS-CoV2 infection</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref5" rid="niceng187er1.s1.3.ref5">Hernandez 2020</a>
|
|
</p>
|
|
<p>Case-control study</p>
|
|
<p>Spain</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=413</p>
|
|
<p>n=216 cases were aged 18 or over admitted to hospital with confirmed COVID-19, n=19 were taking vitamin D supplements.</p>
|
|
<p>n=197 controls were recruited from the Camargo study cohort and were sex-matched with the non-vitamin D supplemented cases.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4 models were conducted:
|
|
<ul><li class="half_rhythm"><div>simple correlation using Spearman rho between 25(OH)D sufficiency categories and clinical indications</div></li><li class="half_rhythm"><div>A multivariable general linear model comparing 25(OH)D levels between COVID-19 patients and controls that took into account confounding factors</div></li><li class="half_rhythm"><div>in COVID-19 patients only, multivariable binary logistic regression between 25(OH)D and disease severity</div></li><li class="half_rhythm"><div>in COVID-19 patients only, multivariable logistic between 25(OH)D and disease severity taking into account confounding factors</div></li></ul></td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Measurements were taken at hospital admission (cases) or during recruitment into study (controls)</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>SARS-CoV-2 infection confirmed by RT-PCR
|
|
<ul><li class="half_rhythm"><div>age</div></li><li class="half_rhythm"><div>smoking, hypertension</div></li><li class="half_rhythm"><div>diabetes mellitus</div></li><li class="half_rhythm"><div>history of cardiovascular events</div></li><li class="half_rhythm"><div>immunosuppression</div></li><li class="half_rhythm"><div>BMI</div></li><li class="half_rhythm"><div>serum corrected calcium</div></li><li class="half_rhythm"><div>glomerular filtration rate</div></li><li class="half_rhythm"><div>month of vitamin D determination</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Composite severity endpoint: admission to the intensive care unit (ICU), requirement for mechanical ventilation, or in-hospital mortality.</div></li><li class="half_rhythm"><div>Also reported:
|
|
<ul><li class="half_rhythm"><div>Length of stay</div></li><li class="half_rhythm"><div>Secondary infection</div></li><li class="half_rhythm"><div>Pneumonia</div></li></ul></div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref6" rid="niceng187er1.s1.3.ref6">Karahan 2020</a>
|
|
</p>
|
|
<p>Case-control study</p>
|
|
<p>Turkey</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=149</p>
|
|
<p>COVID-19 patients who were admitted into the hospital with confirmed COVID-19.</p>
|
|
<p>n=47, moderate COVID-19</p>
|
|
<p>n=102, severe-critical COVID-19</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Compared patients in the moderate arm to the severe/critical arm; and then compared patients who survived and patients who died.</p>
|
|
<p>Pearson’s correlation evaluated the bivariate correlation between the serum 25(OH) vitamin D level and inflammatory marker.</p>
|
|
<p>Univariable and multivariable logistic regression analyses were used to determine the independent associates of mortality.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Measurements taken by electrochemiluminescence at admission.</p>
|
|
<p>Patients were stratified according to their serum 25(OH) vitamin D levels:
|
|
<ul><li class="half_rhythm"><div>≥75 nmol/L: normal</div></li><li class="half_rhythm"><div>51 to 74 nmol/L: insufficiency</div></li><li class="half_rhythm"><div><50 nmol/L: deficiency</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>SARS-CoV-2 infection confirmed by PCR</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Comorbidities</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">In-hospital mortality</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref7" rid="niceng187er1.s1.3.ref7">Kaufman 2020</a>
|
|
</p>
|
|
<p>Retrospective cohort study</p>
|
|
<p>US</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=191779</p>
|
|
<p>Participant data was collected from a Quest Diagnostics database that processed SARS-CoV-2 tests and matched it to data held on individual’s vitamin D results from the preceding 12 months.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Polynomial regression was fitted between vitamin D values and infection.</p>
|
|
<p>Multivariable logistic regression was performed adjusting for confounders.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Measurements taken by electrochemiluminescence or liquid chromatograph/tandem mass spectrometry.</p>
|
|
<p>Patients were stratified according to their serum 25(OH) vitamin D levels:
|
|
<ul><li class="half_rhythm"><div>≥75 nmol/L: optimal</div></li><li class="half_rhythm"><div>51 to 74 nmol/L: suboptimal</div></li><li class="half_rhythm"><div><50 nmol/L: deficiency</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>SARS-CoV-2 infection confirmed by PCR.</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Month of vitamin D test</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SARS-CoV2 infection</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref8" rid="niceng187er1.s1.3.ref8">Macaya 2020</a>
|
|
</p>
|
|
<p>Case series</p>
|
|
<p>Spain</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>admitted to hospital with COVID-19</p>
|
|
<p>n=49 had non-severe COVID-19</p>
|
|
<p>n=31 had severe COVID-19</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Association between the composite COVID-19 outcome and vitamin D level was conducted by multivariable logistic regression adjusting for confounders.</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Measured by chemiluminescent immunoassay at admission or within the previous 3 months.</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>COVID-19 severity</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Obesity</div></li><li class="half_rhythm"><div>Sex</div></li><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Advanced kidney disease</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Composite COVID-19 outcome: death, admission to ICU, need for higher oxygen flow than provided by a nasal cannula.</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref9" rid="niceng187er1.s1.3.ref9">Meltzer 2020</a>
|
|
</p>
|
|
<p>Retrospective cohort study</p>
|
|
<p>US</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N=4313 patients tested for SARS-CoV-2 infection at the university.</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Association between vitamin D status and SARS-CoV-2 infection multivariable generalised linear model with binomial residuals and log-link function was estimated adjusting for confounders</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D measurements were from the preceding 12 months. To account for changes to vitamin D status, status was estimated by taking into account changes to supplements taken. Participants were grouped as follows:
|
|
<ul><li class="half_rhythm"><div>Likely deficient</div></li><li class="half_rhythm"><div>Likely sufficient</div></li><li class="half_rhythm"><div>Last level deficient and treatment increased</div></li><li class="half_rhythm"><div>Last level not deficient and treatment decreased</div></li></ul></td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>SARS-CoV-2 infection confirmed by PCR.</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Sex</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Employee status</div></li><li class="half_rhythm"><div>Vitamin D status</div></li><li class="half_rhythm"><div>Comorbidity indicators</div></li><li class="half_rhythm"><div>BMI</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SARS-CoV2 infection</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref10" rid="niceng187er1.s1.3.ref10">Merzon 2020</a>
|
|
</p>
|
|
<p>Case-control study</p>
|
|
<p>Israel</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=14,000</p>
|
|
<p>People of the Leumit Health Services who were tested for SARS-CoV-2.</p>
|
|
<p>n=782, COVID-19 positive</p>
|
|
<p>n=7025, COVID-19 negative</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Univariate analyses assessed the association between baseline characteristics and COVID-19 infection and hospitalisation.</p>
|
|
<p>Multivariable analyses assessed the association between 25(OH)D levels and COVID-19 infection and hospitalisation, adjusting for confounders.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Measured by chemiluminescence assay.</p>
|
|
<p>Low vitamin D level was considered <75 nmol/L.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>SARS-CoV-2 infection confirmed by RT-PCR</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Demographic variables</div></li><li class="half_rhythm"><div>Psychiatric disorders</div></li><li class="half_rhythm"><div>Somatic disorders</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>SARS-CoV2 infection</p>
|
|
<p>Hospitalisation</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref11" rid="niceng187er1.s1.3.ref11">Radujkovic 2020</a>
|
|
</p>
|
|
<p>Retrospective cohort study</p>
|
|
<p>Germany</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=185</p>
|
|
<p>Consecutive symptomatic SARS-CoV-2-positive patients admitted to hospital</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cox regression was used to assess association between vitamin D status and composite endpoint, adjusted for confounders.</p>
|
|
<p>Survival analysis was conducted by Kaplan–Meier curves.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Samples taken at admission retrospectively measured by immunoassay.</p>
|
|
<p>Low vitamin D level was considered <30 nmol/L</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>SARS-CoV-2 infection measured by RT-PCR</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Gender</div></li><li class="half_rhythm"><div>Comorbidity</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Composite endpoint: invasive mechanical ventilation and/or death.</p>
|
|
<p>All-cause mortality.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref12" rid="niceng187er1.s1.3.ref12">Raisi-Estabragh 2020</a>
|
|
</p>
|
|
<p>Nested case-control study</p>
|
|
<p>UK</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=4510</p>
|
|
<p>People aged 40 to 69 in the UK Biobank study who had taken a SARS-CoV-2 test.</p>
|
|
<p>n=1326, COVID-19 positive</p>
|
|
<p>n=3184, COVID-19 negative</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Univariate logistic regression was performed for every variable individually to assess the association between them and SARS-CoV-2 infection.</p>
|
|
<p>Multivariable logistic regression models were run to associated groups of variables with COVID-19 infection, one of which included vitamin D levels, adjusted for confounders.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Measured at central laboratory at time of recruitment, 2006 to 2010.</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>SARS-CoV-2 infection as recorded by Public Health England</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Sex</div></li><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Vitamin D</div></li><li class="half_rhythm"><div>Season of vitamin D measurement</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SARS-CoV2 infection</td></tr><tr><td headers="hd_h_niceng187er1.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref13" rid="niceng187er1.s1.3.ref13">Ye 2020</a>
|
|
</p>
|
|
<p>Case-control study</p>
|
|
<p>China</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>N=142</p>
|
|
<p>n=62 cases with COVID-19 treated in hospital</p>
|
|
<p>n=80 controls recruited from an examination centre with no medical condition, matched to cases by sex and age.</p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unconditional logistic regression assessing association between all measured risk factors and severe/critical disease, and another for the association between all measured risk factors and cases versus controls.</td><td headers="hd_h_niceng187er1.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Electrochemiluminescence immunoassay on samples taken at admission.</p>
|
|
<p>Patients were stratified according to their serum 25(OH) vitamin D levels:
|
|
<ul><li class="half_rhythm"><div><50 nmol/L: deficient</div></li><li class="half_rhythm"><div>50 to 75 nmol/L: insufficient</div></li><li class="half_rhythm"><div>≥ 75 nmol/L: sufficient</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Dependent variable:</p>
|
|
<p>SARS-CoV-2 infection diagnosed by RNA from throat swab samples.</p>
|
|
<p>Confounders:
|
|
<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Sex</div></li><li class="half_rhythm"><div>Comorbidities</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng187er1.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>COVID-19 severity</p>
|
|
<p>SARS-CoV2 infection</p>
|
|
</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1tab6"><div id="niceng187er1.tab6" class="table"><h3><span class="label">Table 6</span><span class="title">Summary of evidence for the association between vitamin D status and COVID-19 cases</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.tab6_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D</th><th id="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Association</th><th id="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N</th><th id="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adjusted for</th><th id="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Quality</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D level (nmol/L)</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 1.00 (0.998 to 1.01)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cases n=449</p>
|
|
<p>Control n=348,598</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ethnicity, sex, month of assessment, Townsend deprivation quintile, household income, self-reported health rating, smoking status, body mass index (BMI) category, age at assessment, diabetes, SBP, DBP, and long-standing illness, disability or infirmity</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D level (nmol/L)</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 1 (1 to 1)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref12" rid="niceng187er1.s1.3.ref12">Raisi-Esrabragh 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cases n=1326</p>
|
|
<p>Control n=3184</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sex, age and ethnicity</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D level (ng/ml)</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD: −9.3; p<0.001</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref5" rid="niceng187er1.s1.3.ref5">Hernandez 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cases n=197</p>
|
|
<p>Control n=197</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, smoking, hypertension, diabetes mellitus, history of cardiovascular events, immunosuppressio n, body mass index (BMI), serum corrected calcium, glomerular filtration rate and the month of vitamin D determination</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D level (ng/ml)</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.984 (0.983 to 0.986)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref7" rid="niceng187er1.s1.3.ref7">Kaufman 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cohort N=191,779</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Gender, age, latitudes, ethnicity</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D level (nmol/L) by ethnicity</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.90 (0.66 to 1.23)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cases n=449</p>
|
|
<p>Control n=348,598</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ethnicity, sex, month of assessment, Townsend deprivation quintile, household income, self-reported health rating, smoking status, BMI category, age at assessment, diabetes, SBP, DBP, and long-standing illness, disability or infirmity</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D deficiency <25 nmol/L</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.92 (0.71 to 1.21)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cases n=449</p>
|
|
<p>Control n=348,598</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ethnicity, sex, month of assessment, Townsend deprivation quintile, household income, self-reported health rating, smoking status, BMI category, age at assessment, diabetes, SBP, DBP, and long-standing illness, disability or infirmity</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D insufficiency <50 nmol/L</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.88 (0.72 to 1.08)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cases n=449</p>
|
|
<p>Control n=348,598</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ethnicity, sex, month of assessment, Townsend deprivation quintile, household income, self-reported health rating, smoking status, BMI category, age at assessment, diabetes, SBP, DBP, and long-standing illness, disability or infirmity</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D deficient <50 nmol/L</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 1.77 (1.12 to 2.81)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref9" rid="niceng187er1.s1.3.ref9">Meltzer 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Positive n=71</p>
|
|
<p>Negative n=418</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypertension, diabetes, chronic pulmonary disease, pulmonary circulation disorders, depression, immunosuppression, liver disease, and chronic kidney disease.</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Vitamin D suboptimal <75 nmol/L</b>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 1.5 (1.13 to 1.98)</td><td headers="hd_h_niceng187er1.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref10" rid="niceng187er1.s1.3.ref10">Merzon 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cases n=782</p>
|
|
<p>Control n=7025</p>
|
|
</td><td headers="hd_h_niceng187er1.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, ethnicity, smoking, depression/anxiety, schizophrenia, dementia, diabetes, hypertension, cardiovascular disease, chronic lung disease, obesity, BMI and socioeconomic status.</td><td headers="hd_h_niceng187er1.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1tab7"><div id="niceng187er1.tab7" class="table"><h3><span class="label">Table 7</span><span class="title">Summary of evidence for the association between vitamin D status and COVID-19 severity</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.tab7_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcome</th><th id="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Effect</th><th id="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D status</th><th id="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Number of people in study</th><th id="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adjusted for</th><th id="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Quality</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Composite endpoint: (admission to the intensive care unit (ICU), requirement for mechanical ventilation, or in-hospital mortality)</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 1.13 (0.27 to 4.77)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref5" rid="niceng187er1.s1.3.ref5">Hernandez 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D level, nmol/L</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">197</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Smoking, hypertension, diabetes mellitus, history of cardiovascular events, immunosuppression, body mass index, serum corrected calcium, glomerular filtration rate and the month of vitamin D determination.</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Composite endpoint including mechanical ventilation and death</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 6.12 (2.79 to 13.42)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref11" rid="niceng187er1.s1.3.ref11">Radujkovic 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D suboptimal <30 nmol/L</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">185</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender and comorbidities. Includes values for whole cohort not for inpatients only</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Severe/critical cases defined as having one of the following: breathing rate >30/min, O2 saturation ≤93% at rest, PaO2/FiO2 ≤ mmHg or lung imaging shows significant progression, respiratory failure (PaO2 <60mmHg), shock, organ failures that requires ICU care</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 15.18 (1.23 to 187.45)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref13" rid="niceng187er1.s1.3.ref13">Ye 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D deficiency <50 nmol/L</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, sex and comorbidities</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Mortality</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.92 (0.88 to 0.98)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref6" rid="niceng187er1.s1.3.ref6">Karahan 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D level (ng/ml), continuous measure</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">149</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, smoking, hyperlipidaemia, diabetes mellitus, chronic kidney disease, chronic atrial fibrillation, congestive heart failure, acute kidney injury, estimated glomerular filtration rate, haemoglobin, neutrophil count</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Composite outcome defining severity of COVID-19 included death, admission to ICU, and/or need for higher oxygen flow than that provided by a nasal cannula</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 3.2 (0.99 to 11.4)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref8" rid="niceng187er1.s1.3.ref8">Macaya 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D deficiency <50 nmol/L</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">80</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, obesity, severe chronic kidney (CKD) disease, cardiac disease</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Mortality, follow-up to 2 months</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 0.11 (0.03 to 0.48)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref2" rid="niceng187er1.s1.3.ref2">Annweiler 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D sufficient if received a vitamin D booster supplement within a month of COVID-19 diagnosis</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">66</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, number of drugs daily taken, functional abilities, nutritional status, COVID-19 treatment with corticosteroids and/or hydroxychloroquine and/or dedicated antibiotics, and hospitalisation for COVID-19</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>COVID-19 mortality, 14-day follow-up</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 0.07 (0.01 to 0.61)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Annweiler 2020a</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D sufficient if received vitamin D supplements for a year before COVID-19 diagnosis</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, GIR score, severe undernutrition, history of cancer, history of hypertension, history of cardiomyopathy, glycated haemoglobin, number of acute health problems, use of antibiotics, use of systemic corticosteroids, use of treatments of respiratory disorders</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>COVID-19 mortality, 14-day follow-up</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 0.37 (0.06 to 2.21)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Annweiler 2020a</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D sufficient if received vitamin D supplement when diagnosed with COVID-19</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, GIR score, severe undernutrition, history of cancer, history of hypertension, history of cardiomyopathy, glycated haemoglobin, number of acute health problems, use of antibiotics, use of systemic corticosteroids, use of treatments of respiratory disorders</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Severe COVID-19 – World Health Organization Ordinal Scale for Clinical Improvement (OSCI) score ≥ 5</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.08 (0.01 to 0.81)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref2" rid="niceng187er1.s1.3.ref2">Annweiler 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D sufficient if received vitamin D supplements for a year before COVID-19 diagnosis</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, GIR score, severe undernutrition, history of cancer, history of hypertension, history of cardiomyopathy, glycated haemoglobin, number of acute health problems, use of antibiotics, use of systemic corticosteroids, use of treatments of respiratory disorders</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Severe COVID-19 – OSCI score ≥ 5</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.46 (0.07 to 2.85)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Annweiler 2020a</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D sufficient if received vitamin D supplement when diagnosed with COVID-19</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">77</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, GIR score, severe undernutrition, history of cancer, history of hypertension, history of cardiomyopathy, glycated haemoglobin, number of acute health problems, use of antibiotics, use of systemic corticosteroids, use of treatments of respiratory disorders</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Hospitalisation for COVID-19 symptoms</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 1.95 (0.99 to 4.78)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref10" rid="niceng187er1.s1.3.ref10">Merzon 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D suboptimal <75 nmol/L</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7,807</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Multiple conditions and demographic variables</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr><tr><td headers="hd_h_niceng187er1.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<b>Mortality</b>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 14.73 (4.16 to 52.19)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref11" rid="niceng187er1.s1.3.ref11">Radujkovic 2020</a>
|
|
</td><td headers="hd_h_niceng187er1.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D suboptimal (<30 nmol/L)</td><td headers="hd_h_niceng187er1.tab7_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">185</td><td headers="hd_h_niceng187er1.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Age, gender, comorbidity</td><td headers="hd_h_niceng187er1.tab7_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very low</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1appatab1"><div id="niceng187er1.appa.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">Review protocol for review question 1</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appa.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appa.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Field</th><th id="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Content</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROSPERO registration number</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not registered.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review title</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D supplementation for treating COVID-19</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review question</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">What is the clinical effectiveness and safety of vitamin D supplementation for the treatment of COVID-19 in adults, young people and children?</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Objective</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To investigate the clinical efficacy, effectiveness and safety of vitamin D supplementation as a treatment for people with confirmed COVID-19.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Searches</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The following databases will be searched:
|
|
<ul><li class="half_rhythm"><div>Cochrane Central Register of Controlled Trials (CENTRAL)</div></li><li class="half_rhythm"><div>Cochrane Database of Systematic Reviews (CDSR)</div></li><li class="half_rhythm"><div>Embase</div></li><li class="half_rhythm"><div>MEDLINE</div></li></ul>
|
|
Searches will be restricted by:
|
|
<ul><li class="half_rhythm"><div>From year 2002 onwards</div></li><li class="half_rhythm"><div>English language only</div></li><li class="half_rhythm"><div>Human studies only</div></li></ul>
|
|
Other searches:
|
|
<ul><li class="half_rhythm"><div>WHO databases of global research</div></li><li class="half_rhythm"><div><a href="http://ClinicalTrials.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials<wbr style="display:inline-block"></wbr>​.gov</a></div></li><li class="half_rhythm"><div>medRxiv and bioRxiv</div></li></ul>
|
|
There will be no re-run of searches.</p>
|
|
<p>The full search strategies for MEDLINE, Embase and CENTRAL database will be published in the final review.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Condition or domain being studied</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">COVID-19</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Inclusion: Adults, young people and children with confirmed COVID-19.</p>
|
|
<p>Notes:
|
|
<ul><li class="half_rhythm"><div>Other coronavirus such as SARS CoV1 (symptomatic) and MERS <b>will be</b> included</div></li><li class="half_rhythm"><div>People with confirmed COVID-19 who are co-infected with other respiratory viruses <b>will be</b> included</div></li><li class="half_rhythm"><div>Subgroups will be explored, see (section 17).</div></li></ul>
|
|
Exclusion: Adults, young people and children with other respiratory infections unrelated to coronavirus.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D supplementation (all dosages, formulations and routes of administration).</p>
|
|
<p>Note: Vitamin D supplementation as an adjunctive treatment will be included if other treatments are balanced out in the control arm.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparator</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Placebo or standard care or no treatment</p>
|
|
<p>Note: for vitamin D supplementation as an adjunctive treatment, the comparator will be the index treatment(s). For example: Vitamin D + Treatment X versus Treatment X.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Types of study to be included</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Inclusion:
|
|
<ul><li class="half_rhythm"><div>Systematic review of RCTs</div></li><li class="half_rhythm"><div>RCTs (including open-label)</div></li><li class="half_rhythm"><div>Controlled Clinical Trials</div></li></ul>
|
|
If there is insufficient RCT and CCT, prospective and retrospective cohort studies with control arm will be included.</p>
|
|
<p>Exclusion:
|
|
<ul><li class="half_rhythm"><div>Case-control studies</div></li><li class="half_rhythm"><div>Cross section studies</div></li><li class="half_rhythm"><div>Case series and case reports</div></li><li class="half_rhythm"><div>Qualitative studies</div></li></ul></p>
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|
</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other exclusion criteria</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul><li class="half_rhythm"><div>Conference abstracts will be excluded.</div></li><li class="half_rhythm"><div>Preprints will be excluded. However, references of preprints that meet the inclusion criteria will be made available as an appendix to the evidence review. Rationales for exclusion: Unknown authenticity of,
|
|
<ul><li class="half_rhythm"><div>Study design</div></li><li class="half_rhythm"><div>Analytical methods</div></li><li class="half_rhythm"><div>Outcomes data being reported</div></li><li class="half_rhythm"><div>Conclusion being drawn</div></li><li class="half_rhythm"><div>Ethical approval</div></li><li class="half_rhythm"><div>Conflict of interests</div></li></ul></div></li></ul>
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|
Decisions based on data from unknown authenticity may be harmful to patients.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Context</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">It has been hypothesised that vitamin D may have a role in the body’s immune response to respiratory viruses. The 2 major forms of vitamin D, vitamin D3 (colecalciferol) and vitamin D2 (ergocalciferol), are licensed for the prevention and treatment of vitamin D deficiency. Vitamin D supplements are not specifically licensed for preventing or treating any infection, including the novel coronavirus infection that causes COVID-19.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Primary outcomes (critical outcomes)</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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|
<ul><li class="half_rhythm"><div>Mortality (including all cause mortality and COVID-19 related mortality)</div></li><li class="half_rhythm"><div>ICU admission</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary outcomes (important outcomes)</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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|
<ul><li class="half_rhythm"><div>Hospitalisation</div></li><li class="half_rhythm"><div>Use of ventilation (including non-invasive and invasive)</div></li><li class="half_rhythm"><div>Infection cure rates (laboratory/virologically or radiographically confirmed)</div></li><li class="half_rhythm"><div>Time to clinical cure</div></li><li class="half_rhythm"><div>Complications (primary or secondary to COVID-19)</div></li><li class="half_rhythm"><div>Reduction in symptoms and/or symptom severity</div></li><li class="half_rhythm"><div>Adverse effects and safety</div></li><li class="half_rhythm"><div>Tolerability</div></li><li class="half_rhythm"><div>Long COVID</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data extraction (selection and coding)</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>All references identified by the searches and from other sources will be uploaded into EPPI reviewer and de-duplicated. 10% of the abstracts will be reviewed by two reviewers, with any disagreements resolved by discussion or, if necessary, a third independent reviewer.</p>
|
|
<p>The full text of potentially eligible studies will be retrieved and will be assessed in line with the criteria outlined above. A standardised form will be used to extract data (for example, baseline vitamin D status, dosage) from studies (see <a href="https://www.nice.org.uk/process/pmg20/resources" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual, Appendix L</a>).</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Risk of bias (quality) assessment</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Risk of bias will be assessed using the appropriate checklist as described in Developing NICE guidelines: the manual.</p>
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<p>For systematic review, ROBIS will be used</p>
|
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<p>For RCT and CCT, Cochrane RoB 2 tool will be used</p>
|
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<p>For prospective and retrospective cohort study, Cochrane ROBINS-I will be used.</p>
|
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strategy for data synthesis</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Where appropriate, pairwise meta-analysis will be conducted based on Cochrane Handbook for Systematic Reviews of Interventions (version 6.1, 2020)
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<ul><li class="half_rhythm"><div>Heterogeneity will be assessed by visual inspection of 95%CIs, I squared and Chi squared.</div></li><li class="half_rhythm"><div>Where data points are sufficient, sensitivity analysis will be conducted for studies with high risk of bias</div></li><li class="half_rhythm"><div>GRADE will be used to present the evidence.</div></li><li class="half_rhythm"><div>Where data points are sufficient, funnel plot will be used to assess publication bias.</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analysis of sub-groups</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Subgroup effects will be explored for:
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<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Gender</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Comorbidities</div></li><li class="half_rhythm"><div>Body mass index</div></li><li class="half_rhythm"><div>Use of immune suppressing treatments</div></li><li class="half_rhythm"><div>Socioeconomic status</div></li><li class="half_rhythm"><div>Baseline vitamin D status</div></li><li class="half_rhythm"><div>COVID-19 infection severity at point of supplementation</div></li><li class="half_rhythm"><div>Other supplement use</div></li><li class="half_rhythm"><div>Timing of vitamin D measurements (for example, historical, on entry to hospital / intensive care unit)</div></li><li class="half_rhythm"><div>Shielding status</div></li><li class="half_rhythm"><div>Living in care homes</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type and method of review</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Language</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">English</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Country</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review conducted by NICE, England</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anticipated or actual start date</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26/10/2020</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anticipated completion date</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23/11/2020</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Named contact</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<b>5a. Named contact</b>
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</p>
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<p>Toni Tan</p>
|
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<p>Catrin Austin</p>
|
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<p>
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<b>5b. Organisational affiliation of the review</b>
|
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</p>
|
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<p>National Institute for Health and Care Excellence (NICE) and Public Health England (PHE).</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review team members</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">From NICE:
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<ul><li class="half_rhythm"><div>Toni Tan</div></li><li class="half_rhythm"><div>Catrin Austin</div></li><li class="half_rhythm"><div>Thomas Hudson</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Funding sources/sponsor</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This systematic review is being completed by NICE which receives funding from DH&SC, NHSE and PHE.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conflicts of interest</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All guideline committee members and anyone who has direct input into NICE guidelines (including the evidence review team and expert witnesses) must declare any potential conflicts of interest in line with NICE’s code of practice for declaring and dealing with conflicts of interest. Any relevant interests, or changes to interests, will also be declared publicly at the start of each guideline committee meeting. Before each meeting, any potential conflicts of interest will be considered by the guideline committee Chair and a senior member of the development team. Any decisions to exclude a person from all or part of a meeting will be documented. Any changes to a member’s declaration of interests will be recorded in the minutes of the meeting. Declarations of interests will be published with the final guideline.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Collaborators</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Development of this systematic review will be overseen by an advisory committee who will use the review to inform the development of evidence-based recommendations in line with <a href="https://www.nice.org.uk/process/pmg20/resources/appendix-l-interim-process-and-methods-for-guidelines-developed-in-response-to-health-and-social-care-emergencies-8779776589/chapter/who-is-involved" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">section 3 of appendix L of Developing NICE guidelines: the manual</a>. Members of the guideline committee are available on the NICE website.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other registration details</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference/URL for published protocol</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dissemination plans</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICE may use a range of different methods to raise awareness of the guideline. These include standard approaches such as:
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<ul><li class="half_rhythm"><div>notifying registered stakeholders of publication</div></li><li class="half_rhythm"><div>publicising the guideline through NICE’s newsletter and alerts</div></li><li class="half_rhythm"><div>issuing a press release or briefing as appropriate, posting news articles on the NICE website, using social media channels, and publicising the guideline within NICE.</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Keywords</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D, COVID-19</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Details of existing review of same topic by same authors</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Additional information</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Details of final publication</td><td headers="hd_h_niceng187er1.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="http://www.nice.org.uk" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www<wbr style="display:inline-block"></wbr>​.nice.org.uk</a>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1appatab2"><div id="niceng187er1.appa.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Review protocol for review question 2</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appa.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appa.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Field</th><th id="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Content</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROSPERO registration number</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not registered</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review title</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D supplementation for preventing SARS CoV 2 infection (and subsequent COVID-19)</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review question</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">What is the clinical effectiveness and safety of vitamin D supplementation for the prevention of SARS CoV2 infection (and subsequent COVID-19) in adults, young people and children?</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Objective</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To investigate the clinical efficacy, effectiveness and safety of vitamin D supplementation to prevent SARS CoV2 infection (and subsequent COVID-19).</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Searches</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>The following databases will be searched:
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<ul><li class="half_rhythm"><div>Cochrane Central Register of Controlled Trials (CENTRAL)</div></li><li class="half_rhythm"><div>Cochrane Database of Systematic Reviews (CDSR)</div></li><li class="half_rhythm"><div>Embase</div></li><li class="half_rhythm"><div>MEDLINE</div></li></ul>
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Searches will be restricted by:
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<ul><li class="half_rhythm"><div>From year 2002 onwards</div></li><li class="half_rhythm"><div>English language only</div></li><li class="half_rhythm"><div>Human studies only</div></li></ul>
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Other searches:
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<ul><li class="half_rhythm"><div>WHO databases of global research</div></li><li class="half_rhythm"><div><a href="http://ClinicalTrials.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials<wbr style="display:inline-block"></wbr>​.gov</a></div></li><li class="half_rhythm"><div>medRxiv and bioRxiv</div></li></ul>
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There will be no re-run of searches.</p>
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<p>The full search strategies for MEDLINE, Embase and CENTRAL database will be published in the final review.</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Condition or domain being studied</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">COVID-19</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Inclusion:
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<ul><li class="half_rhythm"><div>Adults, young people and children who are not infected with SARS CoV2 (or SAR CoV1 and MERS).</div></li></ul>
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Notes: Studies on specific sub-populations such as those identified as ‘vulnerable’, ‘extremely vulnerable’ or other comorbidities will be included.</p>
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<p>Subgroups will be explored, see (section 17).</p>
|
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<p>Exclusion:</p>
|
|
<p>Adults, young people and children who already have contracted SARS CoV2 at the point of study entry.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Vitamin D supplementation (all dosages, formulations and routes of administration).</p>
|
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<p>Note: Vitamin D supplementation as a combination preventative strategy with other preventative interventions will be included if other preventative interventions are balanced out in the control arm.</p>
|
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparator</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Placebo or no preventative intervention</p>
|
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<p>Note: for vitamin D supplementation as a combination preventative strategy with other preventative interventions, the comparator will be the index preventative intervention(s). For example: Vitamin D + Preventative treatment X versus Preventative treatment X.</p>
|
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Types of study to be included</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Inclusion:
|
|
<ul><li class="half_rhythm"><div>Systematic review of RCTs</div></li><li class="half_rhythm"><div>RCTs (including open-label)</div></li><li class="half_rhythm"><div>Controlled Clinical Trials</div></li></ul>
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If there is insufficient RCT and CCT, prospective and retrospective cohort studies with control arm will be included.</p>
|
|
<p>Exclusion:
|
|
<ul><li class="half_rhythm"><div>Case-control studies</div></li><li class="half_rhythm"><div>Cross section studies</div></li><li class="half_rhythm"><div>Case series and case reports</div></li><li class="half_rhythm"><div>Qualitative studies</div></li></ul></p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other exclusion criteria</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<ul><li class="half_rhythm"><div>Conference abstracts will be excluded.</div></li><li class="half_rhythm"><div>Preprints will be excluded. However, references of preprints that meet the inclusion criteria will be made available as an appendix to the evidence review. Rationales for exclusion: Unknown authenticity of,
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<ul><li class="half_rhythm"><div>Study design</div></li><li class="half_rhythm"><div>Analytical methods</div></li><li class="half_rhythm"><div>Outcomes data being reported</div></li><li class="half_rhythm"><div>Conclusion being drawn</div></li><li class="half_rhythm"><div>Ethical approval</div></li><li class="half_rhythm"><div>Conflict of interests</div></li></ul></div></li></ul>
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Decisions based on data from unknown authenticity may be harmful to patients.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Context</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">It has been hypothesised that vitamin D may have a role in the body’s immune response to respiratory viruses. The 2 major forms of vitamin D, vitamin D3 (colecalciferol) and vitamin D2 (ergocalciferol), are licensed for the prevention and treatment of vitamin D deficiency. Vitamin D supplements are not specifically licensed for preventing or treating any infection, including the novel coronavirus infection that causes COVID-19.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Primary outcomes (critical outcomes)</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Incidence of SARS CoV2 infection (laboratory/virologically confirmed)</div></li><li class="half_rhythm"><div>SARS CoV2 infection rate (laboratory/virologically confirmed)</div></li><li class="half_rhythm"><div>Number of people who developed COVID-19 (laboratory/virologically confirmed)</div></li><li class="half_rhythm"><div>Severity of COVID-19</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Secondary outcomes (important outcomes)</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Mortality</div></li><li class="half_rhythm"><div>Morbidity</div></li><li class="half_rhythm"><div>Adverse effects and safety</div></li><li class="half_rhythm"><div>Poor outcomes (for example, long COVID)</div></li><li class="half_rhythm"><div>Tolerability</div></li><li class="half_rhythm"><div>Adherence</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data extraction (selection and coding)</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>All references identified by the searches and from other sources will be uploaded into EPPI reviewer and de-duplicated. 10% of the abstracts will be reviewed by two reviewers, with any disagreements resolved by discussion or, if necessary, a third independent reviewer.</p>
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<p>The full text of potentially eligible studies will be retrieved and will be assessed in line with the criteria outlined above. A standardised form will be used to extract data (for example, baseline vitamin D status, dosage) from studies (see <a href="https://www.nice.org.uk/process/pmg20/resources" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual, Appendix L</a>).</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Risk of bias (quality) assessment</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Risk of bias will be assessed using the appropriate checklist as described in Developing NICE guidelines: the manual.</p>
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<p>For systematic review, ROBIS will be used</p>
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<p>For RCT and CCT, Cochrane RoB 2 tool will be used</p>
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<p>For prospective and retrospective cohort study, Cochrane ROBINS-I will be used.</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strategy for data synthesis</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Where appropriate, pairwise meta-analysis will be conducted based on Cochrane Handbook for Systematic Reviews of Interventions (version 6.1, 2020)
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<ul><li class="half_rhythm"><div>Heterogeneity will be assessed by visual inspection of 95%CIs, I squared and Chi squared.</div></li><li class="half_rhythm"><div>Where data points are sufficient, sensitivity analysis will be conducted for studies with high risk of bias</div></li><li class="half_rhythm"><div>GRADE will be used to present the evidence.</div></li><li class="half_rhythm"><div>Where data points are sufficient, funnel plot will be used to assess publication bias.</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analysis of sub-groups</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Subgroup effects will be explored for:
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<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Gender</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Comorbidities</div></li><li class="half_rhythm"><div>Body mass index</div></li><li class="half_rhythm"><div>Use of immune suppressing treatments</div></li><li class="half_rhythm"><div>Socioeconomic status</div></li><li class="half_rhythm"><div>Baseline vitamin D status</div></li><li class="half_rhythm"><div>Other supplement use</div></li><li class="half_rhythm"><div>Timing of vitamin D measurements (for example, historical, on entry to hospital / intensive care unit)</div></li><li class="half_rhythm"><div>Shielding status</div></li><li class="half_rhythm"><div>Living in care homes</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type and method of review</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Language</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">English</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Country</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review conducted by NICE, England</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anticipated or actual start date</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26/10/2020</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anticipated completion date</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23/11/2020</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Named contact</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<b>5a. Named contact</b>
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</p>
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<p>Toni Tan</p>
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<p>Catrin Austin</p>
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<p>
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<b>5b. Organisational affiliation of the review</b>
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</p>
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<p>National Institute for Health and Care Excellence (NICE) and Public Health England (PHE)</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review team members</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">From NICE:
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<ul><li class="half_rhythm"><div>Toni Tan</div></li><li class="half_rhythm"><div>Catrin Austin</div></li><li class="half_rhythm"><div>Thomas Hudson</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Funding sources/sponsor</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This systematic review is being completed by NICE which receives funding from DH&SC, NHSE and PHE.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conflicts of interest</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All guideline committee members and anyone who has direct input into NICE guidelines (including the evidence review team and expert witnesses) must declare any potential conflicts of interest in line with NICE’s code of practice for declaring and dealing with conflicts of interest. Any relevant interests, or changes to interests, will also be declared publicly at the start of each guideline committee meeting. Before each meeting, any potential conflicts of interest will be considered by the guideline committee Chair and a senior member of the development team. Any decisions to exclude a person from all or part of a meeting will be documented. Any changes to a member’s declaration of interests will be recorded in the minutes of the meeting. Declarations of interests will be published with the final guideline.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Collaborators</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Development of this systematic review will be overseen by an advisory committee who will use the review to inform the development of evidence-based recommendations in line with <a href="https://www.nice.org.uk/process/pmg20/resources/appendix-l-interim-process-and-methods-for-guidelines-developed-in-response-to-health-and-social-care-emergencies-8779776589/chapter/who-is-involved" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">section 3 of appendix L of Developing NICE guidelines: the manual</a>. Members of the guideline committee are available on the NICE website.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other registration details</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference/URL for published protocol</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dissemination plans</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICE may use a range of different methods to raise awareness of the guideline. These include standard approaches such as:
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<ul><li class="half_rhythm"><div>notifying registered stakeholders of publication</div></li><li class="half_rhythm"><div>publicising the guideline through NICE’s newsletter and alerts</div></li><li class="half_rhythm"><div>issuing a press release or briefing as appropriate, posting news articles on the NICE website, using social media channels, and publicising the guideline within NICE.</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Keywords</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D, COVID-19.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Details of existing review of same topic by same authors</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Additional information</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Details of final publication</td><td headers="hd_h_niceng187er1.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="http://www.nice.org.uk" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www<wbr style="display:inline-block"></wbr>​.nice.org.uk</a>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1appatab3"><div id="niceng187er1.appa.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Review protocol for review question 3</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appa.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appa.tab3_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Field</th><th id="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Content</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROSPERO registration number</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not registered</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review title</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The associations of vitamin D status with COVID-19, severity and poorer outcomes.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review question</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Is vitamin D status independently associated with susceptibility to developing COVID-19, severity of COVID-19, and poorer outcomes from COVID-19 in adults, young people and children?</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Objective</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To investigate whether vitamin D status alone is independently associated with higher risk of contracting COVID-19, higher risk of having more severe COVID-19 infection, and more likely to have poorer outcomes.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Searches</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>The following databases will be searched:
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<ul><li class="half_rhythm"><div>Cochrane Central Register of Controlled Trials (CENTRAL)</div></li><li class="half_rhythm"><div>Cochrane Database of Systematic Reviews (CDSR)</div></li><li class="half_rhythm"><div>Embase</div></li><li class="half_rhythm"><div>MEDLINE</div></li></ul>
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Searches will be restricted by:
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<ul><li class="half_rhythm"><div>From year 2002 onwards</div></li><li class="half_rhythm"><div>English language only</div></li><li class="half_rhythm"><div>Human studies only</div></li></ul>
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Other searches:
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<ul><li class="half_rhythm"><div>WHO databases of global research</div></li><li class="half_rhythm"><div><a href="http://ClinicalTrials.gov" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials<wbr style="display:inline-block"></wbr>​.gov</a></div></li><li class="half_rhythm"><div>medRxiv and bioRxiv</div></li></ul>
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There will be no re-run of searches.</p>
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<p>The full search strategies for MEDLINE, Embase and CENTRAL database will be published in the final review.</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Condition or domain being studied</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">COVID-19</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Inclusion: Adults, young people and children with confirmed COVID-19.</p>
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<p>Note: Other coronavirus such as SARS CoV1 (symptomatic) and MERS will be included as indirect evidence</p>
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<p>Exclusion: Adults, young people and children with other respiratory infections unrelated to coronavirus.</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dependent variable</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D status (as measured by serum/plasma 25(OH)D concentration)</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Independent variables/confounders/effect moderators/effect mediators</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Statistical methods including adjustments will be assessed in included studies for the following (but not limited to):
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<ul><li class="half_rhythm"><div>Age</div></li><li class="half_rhythm"><div>Gender</div></li><li class="half_rhythm"><div>Ethnicity</div></li><li class="half_rhythm"><div>Comorbidities (including those identified as ‘vulnerable’ and ‘extremely vulnerable’)</div></li><li class="half_rhythm"><div>Body mass index</div></li><li class="half_rhythm"><div>Use of immune suppressing treatments</div></li><li class="half_rhythm"><div>Socioeconomic status (for example, deprivation, housing, occupation)</div></li><li class="half_rhythm"><div>Previous history of COVID-19</div></li><li class="half_rhythm"><div>Other supplement use</div></li><li class="half_rhythm"><div>Timing of vitamin D measurements (for example, historical, on entry to hospital / intensive care unit [ICU])</div></li><li class="half_rhythm"><div>Shielding status</div></li><li class="half_rhythm"><div>Living in care homes</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Types of study to be included</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inclusion:
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<ul><li class="half_rhythm"><div>Systematic review of non-randomised studies</div></li><li class="half_rhythm"><div>Prospective and retrospective cohort studies</div></li><li class="half_rhythm"><div>Case-control studies</div></li><li class="half_rhythm"><div>Cross-sectional studies</div></li><li class="half_rhythm"><div>Case series</div></li></ul>
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Exclusion:
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<ul><li class="half_rhythm"><div>Case reports</div></li><li class="half_rhythm"><div>Ecological studies which used either weather patterns (ultraviolet index) or geographical latitude of locations as a proxy for vitamin D alone (not measuring vitamin D or status)</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other exclusion criteria</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Conference abstracts will be excluded.</div></li><li class="half_rhythm"><div>Preprints will be excluded. However, references of preprints that meet the inclusion criteria will be made available as an appendix to the evidence review. Rationales for exclusion: Unknown authenticity of,
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<ul><li class="half_rhythm"><div>Study design</div></li><li class="half_rhythm"><div>Analytical methods</div></li><li class="half_rhythm"><div>Outcomes data being reported</div></li><li class="half_rhythm"><div>Conclusion being drawn</div></li><li class="half_rhythm"><div>Ethical approval</div></li><li class="half_rhythm"><div>Conflict of interests</div></li></ul></div></li></ul>
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Decisions based on data from unknown authenticity may be harmful to patients.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Context</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">It has been hypothesised that vitamin D may have a role in the body’s immune response to respiratory viruses. It has also been hypothesised that vitamin D status could be a contributing risk factor for COVID-19.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes of interest</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Incidence of COVID-19 (laboratory/virologically confirmed)</div></li><li class="half_rhythm"><div>COVID-19 rate (laboratory/virologically confirmed)</div></li><li class="half_rhythm"><div>Severity of confirmed COVID-19 (for example, but not limited to, CDC definition, WHO definition, proxy such as hospitalisation, ventilation, ICU admission, and others)</div></li><li class="half_rhythm"><div>Poor outcomes (for example, mortality, complications, morbidities post infection, long COVID)</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data extraction (selection and coding)</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>All references identified by the searches and from other sources will be uploaded into EPPI reviewer and de-duplicated. 10% of the abstracts will be reviewed by two reviewers, with any disagreements resolved by discussion or, if necessary, a third independent reviewer.</p>
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<p>The full text of potentially eligible studies will be retrieved and will be assessed in line with the criteria outlined above. A standardised form will be used to extract data (for example, baseline vitamin D status, dosage) from studies (see <a href="https://www.nice.org.uk/process/pmg20/resources" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual, Appendix L</a>).</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Risk of bias (quality) assessment</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Risk of bias will be assessed using the appropriate checklist as described in Developing NICE guidelines: the manual.</p>
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<p>For systematic review, ROBIS will be used</p>
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<p>For other study designs, QUIPS (for univariate analysis) and PROBAST (for multivariate analysis) checklist will be used.</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Strategy for data synthesis</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Where appropriate, for example, 2 or more studies that have adjusted for exactly the same confounders, moderators or mediators, pairwise meta-analysis will be conducted based on Cochrane Handbook for Systematic Reviews of Interventions (version 6.1, 2020)
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<ul><li class="half_rhythm"><div>Heterogeneity will be assessed by visual inspection of 95% CIs, I squared and Chi squared.</div></li><li class="half_rhythm"><div>Where data points are sufficient, sensitivity analysis will be conducted for studies with high risk of bias</div></li><li class="half_rhythm"><div>GRADE will be used to present the evidence.</div></li><li class="half_rhythm"><div>Where data points are sufficient, funnel plot will be used to assess publication bias.</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Analysis of sub-groups</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">See section 8</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type and method of review</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Language</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">English</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Country</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review conducted by NICE, England</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anticipated or actual start date</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26/10/2020</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anticipated completion date</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23/11/2020</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Named contact</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<b>5a. Named contact</b>
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</p>
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<p>Toni Tan</p>
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<p>Catrin Austin</p>
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<p>
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<b>5b. Organisational affiliation of the review</b>
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</p>
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<p>National Institute for Health and Care Excellence (NICE) and Public Health England (PHE)</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review team members</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">From NICE:
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<ul><li class="half_rhythm"><div>Toni Tan</div></li><li class="half_rhythm"><div>Catrin Austin</div></li><li class="half_rhythm"><div>Thomas Hudson</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Funding sources/sponsor</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This systematic review is being completed by NICE which receives funding from DH&SC, NHSE and PHE.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conflicts of interest</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All guideline committee members and anyone who has direct input into NICE guidelines (including the evidence review team and expert witnesses) must declare any potential conflicts of interest in line with NICE’s code of practice for declaring and dealing with conflicts of interest. Any relevant interests, or changes to interests, will also be declared publicly at the start of each guideline committee meeting. Before each meeting, any potential conflicts of interest will be considered by the guideline committee Chair and a senior member of the development team. Any decisions to exclude a person from all or part of a meeting will be documented. Any changes to a member’s declaration of interests will be recorded in the minutes of the meeting. Declarations of interests will be published with the final guideline.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Collaborators</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Development of this systematic review will be overseen by an advisory committee who will use the review to inform the development of evidence-based recommendations in line with <a href="https://www.nice.org.uk/process/pmg20/resources/appendix-l-interim-process-and-methods-for-guidelines-developed-in-response-to-health-and-social-care-emergencies-8779776589/chapter/who-is-involved" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">section 3 of appendix L of Developing NICE guidelines: the manual</a>. Members of the guideline committee are available on the NICE website.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other registration details</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference/URL for published protocol</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dissemination plans</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICE may use a range of different methods to raise awareness of the guideline. These include standard approaches such as:
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<ul><li class="half_rhythm"><div>notifying registered stakeholders of publication</div></li><li class="half_rhythm"><div>publicising the guideline through NICE’s newsletter and alerts</div></li><li class="half_rhythm"><div>issuing a press release or briefing as appropriate, posting news articles on the NICE website, using social media channels, and publicising the guideline within NICE.</div></li></ul></td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Keywords</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Vitamin D, COVID-19.</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Details of existing review of same topic by same authors</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Additional information</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr><tr><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Details of final publication</td><td headers="hd_h_niceng187er1.appa.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="http://www.nice.org.uk" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www<wbr style="display:inline-block"></wbr>​.nice.org.uk</a>
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</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobniceng187er1appcfig1"><div id="niceng187er1.appc.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%201.%20Review%20question%201.&p=BOOKS&id=566064_niceng187er1appcf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK566064/bin/niceng187er1appcf1.jpg" alt="Figure 1. Review question 1." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 1</span><span class="title">Review question 1</span></h3></div></article><article data-type="fig" id="figobniceng187er1appcfig2"><div id="niceng187er1.appc.fig2" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20Review%20question%202.&p=BOOKS&id=566064_niceng187er1appcf2.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK566064/bin/niceng187er1appcf2.jpg" alt="Figure 2. Review question 2." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">Review question 2</span></h3></div></article><article data-type="fig" id="figobniceng187er1appcfig3"><div id="niceng187er1.appc.fig3" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%203.%20Review%20question%203.&p=BOOKS&id=566064_niceng187er1appcf3.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK566064/bin/niceng187er1appcf3.jpg" alt="Figure 3. Review question 3." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 3</span><span class="title">Review question 3</span></h3></div></article><article data-type="table-wrap" id="figobniceng187er1appetab1"><div id="niceng187er1.appe.tab1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appe.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appe.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng187er1.appe.tab1_1_1_1_1" colspan="7" rowspan="1" style="text-align:center;vertical-align:middle;">Quality assessment</th><th id="hd_h_niceng187er1.appe.tab1_1_1_1_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Number of participants</th><th id="hd_h_niceng187er1.appe.tab1_1_1_1_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Effect</th><th id="hd_h_niceng187er1.appe.tab1_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng187er1.appe.tab1_1_1_1_4" style="text-align:center;vertical-align:middle;">Quality</th></tr><tr><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1" id="hd_h_niceng187er1.appe.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No of studies</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1" id="hd_h_niceng187er1.appe.tab1_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Design</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1" id="hd_h_niceng187er1.appe.tab1_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk of bias</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1" id="hd_h_niceng187er1.appe.tab1_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconsistency</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1" id="hd_h_niceng187er1.appe.tab1_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Indirectness</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1" id="hd_h_niceng187er1.appe.tab1_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Imprecision</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1" id="hd_h_niceng187er1.appe.tab1_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Other considerations</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_2" id="hd_h_niceng187er1.appe.tab1_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Intervention</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_2" id="hd_h_niceng187er1.appe.tab1_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Control</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_3" id="hd_h_niceng187er1.appe.tab1_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Univariate 95%CI</th><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_3" id="hd_h_niceng187er1.appe.tab1_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Multivariable 95%CI</th></tr></thead><tbody><tr><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_1 hd_h_niceng187er1.appe.tab1_1_1_2_2 hd_h_niceng187er1.appe.tab1_1_1_2_3 hd_h_niceng187er1.appe.tab1_1_1_2_4 hd_h_niceng187er1.appe.tab1_1_1_2_5 hd_h_niceng187er1.appe.tab1_1_1_2_6 hd_h_niceng187er1.appe.tab1_1_1_2_7 hd_h_niceng187er1.appe.tab1_1_1_1_2 hd_h_niceng187er1.appe.tab1_1_1_2_8 hd_h_niceng187er1.appe.tab1_1_1_2_9 hd_h_niceng187er1.appe.tab1_1_1_1_3 hd_h_niceng187er1.appe.tab1_1_1_2_10 hd_h_niceng187er1.appe.tab1_1_1_2_11 hd_h_niceng187er1.appe.tab1_1_1_1_4" id="hd_b_niceng187er1.appe.tab1_1_1_1_1" colspan="12" rowspan="1" style="text-align:left;vertical-align:top;">Odds ratio: ICU admission (follow-up: 2 months or until death; Better indicated by lower values)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_1 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>1</sup></td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_2 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trial</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_3 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>2</sup></td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_4 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_5 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_6 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_7 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">low number of participants</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_2 hd_h_niceng187er1.appe.tab1_1_1_2_8 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">50</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_2 hd_h_niceng187er1.appe.tab1_1_1_2_9 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">26</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_3 hd_h_niceng187er1.appe.tab1_1_1_2_10 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>OR 0.02</p>
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<p>(0.002 to 0.17)</p>
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</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_3 hd_h_niceng187er1.appe.tab1_1_1_2_11 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>Adj OR 0.03<sup>3</sup></p>
|
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<p>(0.003 to 0.25)</p>
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</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_4 hd_b_niceng187er1.appe.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_1 hd_h_niceng187er1.appe.tab1_1_1_2_2 hd_h_niceng187er1.appe.tab1_1_1_2_3 hd_h_niceng187er1.appe.tab1_1_1_2_4 hd_h_niceng187er1.appe.tab1_1_1_2_5 hd_h_niceng187er1.appe.tab1_1_1_2_6 hd_h_niceng187er1.appe.tab1_1_1_2_7 hd_h_niceng187er1.appe.tab1_1_1_1_2 hd_h_niceng187er1.appe.tab1_1_1_2_8 hd_h_niceng187er1.appe.tab1_1_1_2_9 hd_h_niceng187er1.appe.tab1_1_1_1_3 hd_h_niceng187er1.appe.tab1_1_1_2_10 hd_h_niceng187er1.appe.tab1_1_1_2_11 hd_h_niceng187er1.appe.tab1_1_1_1_4" id="hd_b_niceng187er1.appe.tab1_1_1_3_1" colspan="12" rowspan="1" style="text-align:left;vertical-align:top;">Odds ratio: mortality (follow-up: 2 months; Better indicated by lower values)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_1 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>1</sup></td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_2 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trial</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_3 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>2</sup></td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_4 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_5 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_6 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_1 hd_h_niceng187er1.appe.tab1_1_1_2_7 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">low number of participants</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_2 hd_h_niceng187er1.appe.tab1_1_1_2_8 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">50</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_2 hd_h_niceng187er1.appe.tab1_1_1_2_9 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">26</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_3 hd_h_niceng187er1.appe.tab1_1_1_2_10 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>OR 0.097<sup>4</sup></p>
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<p>(0.004 to 2.99)</p>
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</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_3 hd_h_niceng187er1.appe.tab1_1_1_2_11 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td><td headers="hd_h_niceng187er1.appe.tab1_1_1_1_4 hd_b_niceng187er1.appe.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="niceng187er1.appe.tab1_1"><p class="no_margin">
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<a class="bibr" href="#niceng187er1.s1.3.ref1" rid="niceng187er1.s1.3.ref1">Entrenas Castillo 2020</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="niceng187er1.appe.tab1_2"><p class="no_margin">Downgraded by 2 levels: Reported outcome, mortality, not analysed in multivariable analysis. Only ICU was reported in this way, even though they are both listed on the clinical trials register as outcomes. Adjustment for multivariable analysis not fully explored or reported, only hypertension and diabetes are reported as definitively included in the model but does include “others”.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="niceng187er1.appe.tab1_3"><p class="no_margin">Diabetes and hypertension were unbalanced after randomisation so were adjusted for in multivariable analysis.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="niceng187er1.appe.tab1_4"><p class="no_margin">No events in intervention arm. 2 events in control arm. NICE-calculated OR.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng187er1appetab2"><div id="niceng187er1.appe.tab2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appe.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appe.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng187er1.appe.tab2_1_1_1_1" colspan="7" rowspan="1" style="text-align:center;vertical-align:middle;">Quality assessment</th><th id="hd_h_niceng187er1.appe.tab2_1_1_1_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Effect</th><th id="hd_h_niceng187er1.appe.tab2_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng187er1.appe.tab2_1_1_1_3" style="text-align:center;vertical-align:middle;">Quality</th></tr><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1" id="hd_h_niceng187er1.appe.tab2_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No of studies</th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1" id="hd_h_niceng187er1.appe.tab2_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Design <i>N</i></th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1" id="hd_h_niceng187er1.appe.tab2_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk of bias</th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1" id="hd_h_niceng187er1.appe.tab2_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconsistency</th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1" id="hd_h_niceng187er1.appe.tab2_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Indirectness</th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1" id="hd_h_niceng187er1.appe.tab2_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Imprecision</th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1" id="hd_h_niceng187er1.appe.tab2_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Other considerations</th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_2" id="hd_h_niceng187er1.appe.tab2_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Univariate 95%CI</th><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_2" id="hd_h_niceng187er1.appe.tab2_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Multivariable 95%CI</th></tr></thead><tbody><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_h_niceng187er1.appe.tab2_1_1_1_3" id="hd_b_niceng187er1.appe.tab2_1_1_1_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">Vitamin D status definition: Vitamin D level (nmol/L)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>1</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Case control</p>
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<p>Cases n=449</p>
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<p>Control n=348,598</p>
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</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>15</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious indirectness<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>OR 0.99</p>
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<p>(0.99 to 0.999)</p>
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</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>Adj OR 1.00<sup>2</sup></p>
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<p>(0.998 to 1.01)</p>
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</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Case control</p>
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<p>Cases n=1326</p>
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<p>Control n=3184</p>
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</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>15</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">OR 1 (0.99 to 1)</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>Adj OR 1<sup>4</sup></p>
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<p>(1 to 1)</p>
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</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_h_niceng187er1.appe.tab2_1_1_1_3" id="hd_b_niceng187er1.appe.tab2_1_1_4_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">Vitamin D status definition: Vitamin D level (ng/ml)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>5</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Case control</p>
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<p>Cases n=197</p>
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<p>Control n=197</p>
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</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>16</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No serious indirectness<sup>6</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious imprecision<sup>7</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>Mean difference<sup>8</sup></p>
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<p>Case=11.9 ng/ml</p>
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<p>Control=21.2 ng/ml</p>
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<p>MD= −9.3 ng/ml</p>
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<p>(p<0.0001)</p>
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|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>9</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Cohort</p>
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<p>N=191,779</p>
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<p>Unclear no. of positive cases</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>15</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious indirectness<sup>10</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 0.984<sup>11</sup></p>
|
|
<p>(0.983 to 0.986)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_4_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_h_niceng187er1.appe.tab2_1_1_1_3" id="hd_b_niceng187er1.appe.tab2_1_1_7_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">Vitamin D status definition: Vitamin D level (nmol/L)*Ethnicity interaction term<sup>19</sup></th></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>1</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Case control</p>
|
|
<p>Cases n=449</p>
|
|
<p>Control n=348,598</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>15</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>2</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 0.90<sup>2</sup></p>
|
|
<p>(0.66 to 1.23)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_h_niceng187er1.appe.tab2_1_1_1_3" id="hd_b_niceng187er1.appe.tab2_1_1_9_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">Vitamin D status definition: Vitamin D deficient (<25 nmol/L)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>1</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Case control</p>
|
|
<p>Cases n=449</p>
|
|
<p>Control n=348,598</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>15</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>OR 1.37</p>
|
|
<p>(1.07 to 1.76)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 0.92<sup>2</sup></p>
|
|
<p>(0.71 to 1.21)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_h_niceng187er1.appe.tab2_1_1_1_3" id="hd_b_niceng187er1.appe.tab2_1_1_11_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">Vitamin D status definition: Vitamin D insufficient (<50 nmol/L)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>1</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Case control</p>
|
|
<p>Cases n=449</p>
|
|
<p>Control n=348,598</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>15</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>OR 1.19</p>
|
|
<p>(0.99 to 1.44)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 0.88<sup>2</sup></p>
|
|
<p>(0.72 to 1.08)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_h_niceng187er1.appe.tab2_1_1_1_3" id="hd_b_niceng187er1.appe.tab2_1_1_13_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">Vitamin D status definition: Vitamin D deficient (<20 ng/mL)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>12</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>Positive n=71</p>
|
|
<p>Negative n=418</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>16</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>20</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 1.77<sup>14</sup></p>
|
|
<p>(1.12 to 2.81)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_h_niceng187er1.appe.tab2_1_1_1_3" id="hd_b_niceng187er1.appe.tab2_1_1_15_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">Vitamin D status definition: Vitamin D suboptimal (<30 ng/mL)</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_1 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>17</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_2 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Case control</p>
|
|
<p>Cases n=782</p>
|
|
<p>Control n=7025</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_3 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>16</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_4 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_5 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>20</sup></td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_6 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_1 hd_h_niceng187er1.appe.tab2_1_1_2_7 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_8 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>OR 1.58</p>
|
|
<p>(1.24 to 2.01)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_2 hd_h_niceng187er1.appe.tab2_1_1_2_9 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 1.5<sup>18</sup></p>
|
|
<p>(1.13 to 1.98)</p>
|
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</td><td headers="hd_h_niceng187er1.appe.tab2_1_1_1_3 hd_b_niceng187er1.appe.tab2_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="niceng187er1.appe.tab2_1"><p class="no_margin">
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<a class="bibr" href="#niceng187er1.s1.3.ref4" rid="niceng187er1.s1.3.ref4">Hastie 2020</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="niceng187er1.appe.tab2_2"><p class="no_margin">Adjusted for ethnicity, sex, month of assessment, Townsend deprivation quintile, household income, self-reported health rating, smoking status, BMI category, age at assessment, diabetes, SBP, DBP, and long-standing illness, disability or infirmity.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="niceng187er1.appe.tab2_3"><p class="no_margin">
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<a class="bibr" href="#niceng187er1.s1.3.ref12" rid="niceng187er1.s1.3.ref12">Raisi-Esrabragh 2020</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="niceng187er1.appe.tab2_4"><p class="no_margin">Adjusted for sex, age and ethnicity.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="niceng187er1.appe.tab2_5"><p class="no_margin">
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<a class="bibr" href="#niceng187er1.s1.3.ref5" rid="niceng187er1.s1.3.ref5">Hernandez 2020</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>6</dt><dd><div id="niceng187er1.appe.tab2_6"><p class="no_margin">No downgrade as the historical control is in 2019, assuming population profiles have not changed since.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7</dt><dd><div id="niceng187er1.appe.tab2_7"><p class="no_margin">Downgrade 2 levels: small sample size assessed against [n = 100+50i], where i = number of independent variables adjusted.</p></div></dd></dl><dl class="bkr_refwrap"><dt>8</dt><dd><div id="niceng187er1.appe.tab2_8"><p class="no_margin">Adjusted for age, smoking, hypertension, diabetes mellitus, history of cardiovascular events, immunosuppression, body mass index, serum corrected calcium, glomerular filtration rate and the month of vitamin D determination.</p></div></dd></dl><dl class="bkr_refwrap"><dt>9</dt><dd><div id="niceng187er1.appe.tab2_9"><p class="no_margin">
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<a class="bibr" href="#niceng187er1.s1.3.ref7" rid="niceng187er1.s1.3.ref7">Kaufman 2020</a>
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|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>10</dt><dd><div id="niceng187er1.appe.tab2_10"><p class="no_margin">Downgrade 2 levels: Vitamin status data was historical (preceding 12 months) where vitamin level may have changed before SAR-CoV-2 testing. Also, the outcome is SAR-CoV-2 positive, not COVID-19 (unclear proportion of asymptomatic positive cases).</p></div></dd></dl><dl class="bkr_refwrap"><dt>11</dt><dd><div id="niceng187er1.appe.tab2_11"><p class="no_margin">Adjusted for gender, age, latitudes, ethnicity.</p></div></dd></dl><dl class="bkr_refwrap"><dt>12</dt><dd><div id="niceng187er1.appe.tab2_12"><p class="no_margin">
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<a class="bibr" href="#niceng187er1.s1.3.ref9" rid="niceng187er1.s1.3.ref9">Meltzer 2020</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>13</dt><dd><div id="niceng187er1.appe.tab2_13"><p class="no_margin">Downgrade 2 level: Vitamin D status and demographic data are over a decade old.</p></div></dd></dl><dl class="bkr_refwrap"><dt>14</dt><dd><div id="niceng187er1.appe.tab2_14"><p class="no_margin">Adjusted for hypertension, diabetes, chronic pulmonary disease, pulmonary circulation disorders, depression, immunosuppression, liver disease, and chronic kidney disease.</p></div></dd></dl><dl class="bkr_refwrap"><dt>15</dt><dd><div id="niceng187er1.appe.tab2_15"><p class="no_margin">Downgrade 2 levels: high risk of bias assessed by QUIPS checklist.</p></div></dd></dl><dl class="bkr_refwrap"><dt>16</dt><dd><div id="niceng187er1.appe.tab2_16"><p class="no_margin">Downgrade 1 level: moderate risk of bias assessed by QUIPS checklist.</p></div></dd></dl><dl class="bkr_refwrap"><dt>17</dt><dd><div id="niceng187er1.appe.tab2_17"><p class="no_margin">
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<a class="bibr" href="#niceng187er1.s1.3.ref10" rid="niceng187er1.s1.3.ref10">Merzon 2020</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>18</dt><dd><div id="niceng187er1.appe.tab2_18"><p class="no_margin">Adjusted for multiple conditions and demographic variables.</p></div></dd></dl><dl class="bkr_refwrap"><dt>19</dt><dd><div id="niceng187er1.appe.tab2_19"><p class="no_margin">This means to explore whether Ethnicity is an effect moderator of vitamin D level which impacts on its association with COVID-19 cases. The non-significant result suggested ethnicity has no interaction with vitamin D level and its association with COVID-19 cases.</p></div></dd></dl><dl class="bkr_refwrap"><dt>20</dt><dd><div id="niceng187er1.appe.tab2_20"><p class="no_margin">Downgrade 1 level: Vitamin D status are historical.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng187er1appetab3"><div id="niceng187er1.appe.tab3" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appe.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appe.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng187er1.appe.tab3_1_1_1_1" colspan="7" rowspan="1" style="text-align:center;vertical-align:middle;">Quality assessment</th><th id="hd_h_niceng187er1.appe.tab3_1_1_1_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Effect</th><th id="hd_h_niceng187er1.appe.tab3_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng187er1.appe.tab3_1_1_1_3" style="text-align:center;vertical-align:middle;">Quality</th></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1" id="hd_h_niceng187er1.appe.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No of studies</th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1" id="hd_h_niceng187er1.appe.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Design <i>N</i></th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1" id="hd_h_niceng187er1.appe.tab3_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk of bias</th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1" id="hd_h_niceng187er1.appe.tab3_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconsistency</th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1" id="hd_h_niceng187er1.appe.tab3_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Indirectness</th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1" id="hd_h_niceng187er1.appe.tab3_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Imprecision</th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1" id="hd_h_niceng187er1.appe.tab3_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Other considerations</th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_2" id="hd_h_niceng187er1.appe.tab3_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Univariate 95%CI</th><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_2" id="hd_h_niceng187er1.appe.tab3_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Multivariable 95%CI</th></tr></thead><tbody><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_1_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
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<p>Vitamin D status definition: Vitamin D level (nmol/L)</p>
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<p>Severity definition: composite severity endpoint (admission to the intensive care unit (ICU), requirement for mechanical ventilation, or in-hospital mortality)</p>
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|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>1</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Case series<sup>2</sup></p>
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<p>n=197</p>
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</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>OR 1.55</p>
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|
<p>(0.66 to 3.65)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>Adj OR 1.13<sup>4</sup></p>
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<p>(0.27 to 4.77)</p>
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|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_3_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
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<p>Vitamin D status definition: Vitamin D suboptimal (<12 ng/ml)</p>
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<p>Severity definition: composite endpoint including mechanical ventilation and death</p>
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</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>5</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Cohort</p>
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<p>n=185</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>20</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>HR 7.66</p>
|
|
<p>(3.53 to 16.63)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj HR 6.12<sup>6</sup></p>
|
|
<p>(2.79 to 13.42)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_5_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: Vitamin D deficiency (<50 nmol/L)</p>
|
|
<p>Severity definition: severe/critical cases defined as having one of the following: breathing rate >30/min, O<sup>2</sup> saturation ≤93% at rest, PaO2/FiO2 ≤mmHg or lung imaging shows significant progression, respiratory failure (PaO<sup>2</sup> <60mmHg), shock, organ failures that requires ICU care</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>7</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Case control</p>
|
|
<p>COVID-19 positive</p>
|
|
<p>n=60</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>OR 7.11</p>
|
|
<p>(1.36 to 37.16)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 15.18<sup>8</sup></p>
|
|
<p>(1.23 to 187.45)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_7_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: Vitamin D level (ng/mL)</p>
|
|
<p>Severity definition (univariate): Moderate – fever and pulmonary symptoms with pneumonia. Severe-Critical – respiratory distress, O<sup>2</sup> saturation ≤93% at rest, PaO2/FiO2 ≤mmHg or chest imaging shows lesion, respiratory failure (mechanical ventilation), shock, organ failures that requires ICU care Severity definition (multivariable): Mortality</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>9</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>n=149</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>20</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>24</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>7</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Mean difference (SD)</p>
|
|
<p>Moderate = 26.3 (8.4)</p>
|
|
<p>Severe-Critical = 10.1 (6.2)</p>
|
|
<p>MD = −16.2 (−18.6 to −13.8)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 0.92<sup>10</sup></p>
|
|
<p>(0.88 to 0.98)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_9_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: Vitamin D deficiency as <20 ng/mL</p>
|
|
<p>Severity definition: composite outcome defining severity of COVID-19 included death, admission to ICU, and/or need for higher oxygen flow than that provided by a nasal cannula.</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>11</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Case series</p>
|
|
<p>n=80</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 3.2<sup>12</sup></p>
|
|
<p>(0.9 to 11.4)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_11_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: vitamin D sufficient if received a vitamin D booster supplement within a month of COVID-19 diagnosis.</p>
|
|
<p>Severity definition: mortality, follow-up up to 2 months.</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>14</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>n=66</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>25</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>HR 0.21</p>
|
|
<p>(0.07 to 0.63)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj HR 0.11<sup>15</sup></p>
|
|
<p>(0.03 to 0.48)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_13_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: vitamin D sufficient if received vitamin D supplements for a year before COVID-19 diagnosis</p>
|
|
<p>Severity definition: 14-day COVID-19 mortality</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>16</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>n=77</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj HR 0.07<sup>17</sup></p>
|
|
<p>(0.01 to 0.61)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_15_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: vitamin D sufficient if received vitamin D supplement when diagnosed with COVID-19</p>
|
|
<p>Severity definition: 14-day COVID-19 mortality</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>16</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>n=77</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj HR 0.37<sup>17</sup></p>
|
|
<p>(0.06 to 2.21)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_17_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: vitamin D sufficient if received vitamin D supplements for a year before COVID-19 diagnosis</p>
|
|
<p>Severity definition: Severe COVID-19 – OSCI score ≥ 5</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>16</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>n=77</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 0.08<sup>17</sup></p>
|
|
<p>(0.01 to 0.81)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_19_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: vitamin D sufficient if received vitamin D supplement when diagnosed with COVID-19</p>
|
|
<p>Severity definition: Severe COVID-19 – OSCI score ≥ 5</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>16</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>n=77</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Very serious<sup>13</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">_</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 0.46<sup>17</sup></p>
|
|
<p>(0.07 to 2.85)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_21_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: Vitamin D suboptimal (<30 ng/mL)</p>
|
|
<p>Severity definition: hospitalisation for COVID-19 symptoms</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>18</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Case control</p>
|
|
<p>n=7807</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>20</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious indirectness<sup>19</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>OR 2.09</p>
|
|
<p>(1.01 to 4.31)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj OR 1.95<sup>21</sup></p>
|
|
<p>(0.99 to 4.78)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">LOW</td></tr><tr><th headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_h_niceng187er1.appe.tab3_1_1_1_3" id="hd_b_niceng187er1.appe.tab3_1_1_23_1" colspan="10" rowspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Vitamin D status definition: Vitamin D suboptimal (<12 nmol/L)</p>
|
|
<p>Severity definition: mortality</p>
|
|
</th></tr><tr><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_1 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1<sup>22</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_2 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Cohort</p>
|
|
<p>n=185</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_3 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Serious<sup>20</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_4 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_5 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_6 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious imprecision<sup>3</sup></td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_1 hd_h_niceng187er1.appe.tab3_1_1_2_7 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_8 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>HR 18.05</p>
|
|
<p>(5.14 to 63.43)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_2 hd_h_niceng187er1.appe.tab3_1_1_2_9 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>Adj HR 14.73<sup>23</sup></p>
|
|
<p>(4.16 to 52.19)</p>
|
|
</td><td headers="hd_h_niceng187er1.appe.tab3_1_1_1_3 hd_b_niceng187er1.appe.tab3_1_1_23_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">VERY LOW</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="niceng187er1.appe.tab3_1"><p class="no_margin">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref5" rid="niceng187er1.s1.3.ref5">Hernandez 2020</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="niceng187er1.appe.tab3_2"><p class="no_margin">This is sub-analysis of cases only from <a class="bibr" href="#niceng187er1.s1.3.ref5" rid="niceng187er1.s1.3.ref5">Hernandez 2020</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="niceng187er1.appe.tab3_3"><p class="no_margin">Downgrade 2 levels: very small sample size assessed against [n = 100+50i], where i = number of independent variables adjusted.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="niceng187er1.appe.tab3_4"><p class="no_margin">Adjusted for age, smoking, hypertension, diabetes mellitus, history of cardiovascular events, immunosuppression, body mass index, serum corrected calcium, glomerular filtration rate and the month of vitamin D determination.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="niceng187er1.appe.tab3_5"><p class="no_margin">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref11" rid="niceng187er1.s1.3.ref11">Radujkovic 2020</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>6</dt><dd><div id="niceng187er1.appe.tab3_6"><p class="no_margin">Adjusted for age, gender and comorbidities. Includes values for whole cohort not for inpatients only.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7</dt><dd><div id="niceng187er1.appe.tab3_7"><p class="no_margin"><a class="bibr" href="#niceng187er1.s1.3.ref13" rid="niceng187er1.s1.3.ref13">Ye 2020</a> – values presented in GRADE table are compared with mild/moderate cases.</p></div></dd></dl><dl class="bkr_refwrap"><dt>8</dt><dd><div id="niceng187er1.appe.tab3_8"><p class="no_margin">Adjusted for age, sex and comorbidities.</p></div></dd></dl><dl class="bkr_refwrap"><dt>9</dt><dd><div id="niceng187er1.appe.tab3_9"><p class="no_margin"><a class="bibr" href="#niceng187er1.s1.3.ref6" rid="niceng187er1.s1.3.ref6">Karahan 2020</a> – Cohort of COVID-19 positive patients with moderate or severe/critical condition.</p></div></dd></dl><dl class="bkr_refwrap"><dt>10</dt><dd><div id="niceng187er1.appe.tab3_10"><p class="no_margin">Adjusted for age, smoking, hyperlipidaemia, diabetes mellitus, chronic kidney disease, chronic atrial fibrillation, congestive heart failure, acute kidney injury, eGFR, haemoglobin, neutrophil count.</p></div></dd></dl><dl class="bkr_refwrap"><dt>11</dt><dd><div id="niceng187er1.appe.tab3_11"><p class="no_margin">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref8" rid="niceng187er1.s1.3.ref8">Macaya 2020</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>12</dt><dd><div id="niceng187er1.appe.tab3_12"><p class="no_margin">Adjusted for age, gender, obesity, severe CKD, cardiac disease.</p></div></dd></dl><dl class="bkr_refwrap"><dt>13</dt><dd><div id="niceng187er1.appe.tab3_13"><p class="no_margin">Downgrade 2 levels: high risk of bias assessed by QUIPS checklist.</p></div></dd></dl><dl class="bkr_refwrap"><dt>14</dt><dd><div id="niceng187er1.appe.tab3_14"><p class="no_margin">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref2" rid="niceng187er1.s1.3.ref2">Annweiler 2020</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>15</dt><dd><div id="niceng187er1.appe.tab3_15"><p class="no_margin">Adjusted for age, gender, number of drugs daily taken, functional abilities, nutritional status, COVID-19 treatment with corticosteroids and/or hydroxychloroquine and/or dedicated antibiotics, and hospitalization for COVID-19.</p></div></dd></dl><dl class="bkr_refwrap"><dt>16</dt><dd><div id="niceng187er1.appe.tab3_16"><p class="no_margin">Annweiler 2020a</p></div></dd></dl><dl class="bkr_refwrap"><dt>17</dt><dd><div id="niceng187er1.appe.tab3_17"><p class="no_margin">Compared with non-supplemented group diagnosed with COVID-19. Adjusted for age, gender, GIR score, severe undernutrition, history of cancer, history of hypertension, history of cardiomyopathy, glycated haemoglobin, number of acute health problems, use of antibiotics, use of systemic corticosteroids, use of treatments of respiratory disorders.</p></div></dd></dl><dl class="bkr_refwrap"><dt>18</dt><dd><div id="niceng187er1.appe.tab3_18"><p class="no_margin">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref10" rid="niceng187er1.s1.3.ref10">Merzon 2020</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>19</dt><dd><div id="niceng187er1.appe.tab3_19"><p class="no_margin">Historic vitamin D values used for association.</p></div></dd></dl><dl class="bkr_refwrap"><dt>20</dt><dd><div id="niceng187er1.appe.tab3_20"><p class="no_margin">Downgrade 1 level: moderate risk of bias assessed by QUIPS checklist.</p></div></dd></dl><dl class="bkr_refwrap"><dt>21</dt><dd><div id="niceng187er1.appe.tab3_21"><p class="no_margin">Adjusted for multiple conditions and demographic variables.</p></div></dd></dl><dl class="bkr_refwrap"><dt>22</dt><dd><div id="niceng187er1.appe.tab3_22"><p class="no_margin">
|
|
<a class="bibr" href="#niceng187er1.s1.3.ref11" rid="niceng187er1.s1.3.ref11">Radujkovic 2020</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>23</dt><dd><div id="niceng187er1.appe.tab3_23"><p class="no_margin">Adjusted for age, gender, comorbidity.</p></div></dd></dl><dl class="bkr_refwrap"><dt>24</dt><dd><div id="niceng187er1.appe.tab3_24"><p class="no_margin">Downgrade 1 level: People with mild severity of COVID-19 were purposely excluded.</p></div></dd></dl><dl class="bkr_refwrap"><dt>25</dt><dd><div id="niceng187er1.appe.tab3_25"><p class="no_margin">Downgraded 1 level: vitamin dosing occurs before and after infection diagnosis causing problems with temporal separation of events.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng187er1appgtab1"><div id="niceng187er1.appg.tab1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appg.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appg.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.appg.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng187er1.appg.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Code [Reason]</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.appg.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Lee, Joseph, van Hecke, Oliver, Roberts, Nia
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et al. (2020) Vitamin D: A rapid review of the evidence for treatment or prevention in COVID-19.
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</td><td headers="hd_h_niceng187er1.appg.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>- Not a peer-reviewed publication</p>
|
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<p><i>A review published by CEBM posted as a webpage and not peer-reviewed</i>.</p>
|
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</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Tan, Chuen Wen, Ho, Liam Pock, Kalimuddin, Shirin
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et al. (2020) Cohort study to evaluate effect of vitamin D, magnesium, and vitamin B12 in combination on severe outcome progression in older patients with coronavirus (COVID-19). Nutrition (Burbank, Los Angeles County, Calif.)
|
|
7980: 111017 [<a href="/pmc/articles/PMC7832811/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7832811</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33039952" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33039952</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Comparator in study does not match that specified in protocol</p>
|
|
<p><i>Vitamin D was used as a combination therapy, which was not balanced in the comparator arm</i>.</p>
|
|
</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1appgtab2"><div id="niceng187er1.appg.tab2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appg.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appg.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.appg.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng187er1.appg.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Code [Reason]</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.appg.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sharma, S.K., Mudgal, S.K., Pai, V.S.
|
|
et al. (2020) Vitamin d: A cheap yet effective bullet against coronavirus disease-19 - are we convinced yet?. National Journal of Physiology, Pharmacy and Pharmacology
|
|
10(7): 511–518
|
|
</td><td headers="hd_h_niceng187er1.appg.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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Yousfi, Narimen, Bragazzi, Nicola Luigi, Briki, Walid
|
|
et al. (2020) The COVID-19 pandemic: how to maintain a healthy immune system during the lockdown - a multidisciplinary approach with special focus on athletes. Biology of sport
|
|
37(3): 211–216 [<a href="/pmc/articles/PMC7433333/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7433333</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32879542" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32879542</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng187er1appgtab3"><div id="niceng187er1.appg.tab3" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK566064/table/niceng187er1.appg.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng187er1.appg.tab3_lrgtbl__"><table><thead><tr><th id="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Code [Reason]</th></tr></thead><tbody><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Abrishami, Alireza, Dalili, Nooshin, Mohammadi Torbati, Peyman
|
|
et al. (2020) Possible association of vitamin D status with lung involvement and outcome in patients with COVID-19: a retrospective study. European journal of nutrition [<a href="/pmc/articles/PMC7595877/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7595877</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33123774" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33123774</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unclear what had been adjusted in the meta-analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Alexander, Jan, Tinkov, Alexey, Strand, Tor A
|
|
et al. (2020) Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19. Nutrients
|
|
12(8) [<a href="/pmc/articles/PMC7468884/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7468884</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32784601" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32784601</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Ali, Nurshad (2020) Role of vitamin D in preventing of COVID-19 infection, progression and severity. Journal of infection and public health
|
|
13(10): 1373–1380 [<a href="/pmc/articles/PMC7305922/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7305922</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32605780" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32605780</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Anonymous (2020) Do Low Vitamin D Levels Increase COVID-19 Risk?. The American journal of nursing
|
|
120(11): 16 [<a href="https://pubmed.ncbi.nlm.nih.gov/33105209" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33105209</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Not a relevant study design</p>
|
|
<p>
|
|
<i>Letter to the journal</i>
|
|
</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arvinte, Cristian; Singh, Maharaj; Marik, Paul E (2020) Serum Levels of Vitamin C and Vitamin D in a Cohort of Critically Ill COVID-19 Patients of a North American Community Hospital Intensive Care Unit in May 2020: A Pilot Study. Medicine in drug discovery
|
|
8: 100064 [<a href="/pmc/articles/PMC7499070/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7499070</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32964205" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32964205</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Dependent variable of interest is vitamin C, not vitamin D</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Baktash, Vadir, Hosack, Tom, Patel, Nishil
|
|
et al. (2020) Vitamin D status and outcomes for hospitalised older patients with COVID-19. Postgraduate medical journal [<a href="/pmc/articles/PMC7456620/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7456620</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32855214" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32855214</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p>
|
|
<i>Unadjusted analyses</i>
|
|
</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Benskin, Linda L (2020) A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency. Frontiers in public health
|
|
8: 513 [<a href="/pmc/articles/PMC7513835/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7513835</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33014983" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33014983</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Carpagnano, G E, Di Lecce, V, Quaranta, V N
|
|
et al. (2020) Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. Journal of endocrinological investigation [<a href="/pmc/articles/PMC7415009/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7415009</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32772324" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32772324</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
D’Avolio, Antonio, Avataneo, Valeria, Manca, Alessandra
|
|
et al. (2020) 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients
|
|
12(5) [<a href="/pmc/articles/PMC7285131/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7285131</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32397511" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32397511</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
de Lucena, Thays Maria Costa, da Silva Santos, Ariane Fernandes, de Lima, Brenda Regina
|
|
et al. (2020) Mechanism of inflammatory response in associated comorbidities in COVID-19. Diabetes & metabolic syndrome
|
|
14(4): 597–600 [<a href="/pmc/articles/PMC7215143/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7215143</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32417709" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32417709</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Review article but not a systematic review</p>
|
|
<p><i>Review methodology states that it systematically searched databases but no review protocol was provided. Review details physiology of vitamin D in the immune response but does not provide studies that show effectiveness of vitamin D in prevention or treatment, or the association between vitamin D status and covid-19 infection</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Eugene, Merzon, Dmitry, Tworowski, Alessandro, Gorohovski
|
|
et al. Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study. [<a href="/pmc/articles/PMC7404739/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7404739</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32700398" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32700398</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Duplicate reference</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Fasano, Alfonso, Cereda, Emanuele, Barichella, Michela
|
|
et al. (2020) COVID-19 in Parkinson’s Disease Patients Living in Lombardy, Italy. Mov. Disord [<a href="/pmc/articles/PMC7300944/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7300944</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32484584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32484584</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>The study included ‘probable’ unconfirmed cases in the analysis, and the analysis is unadjusted</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Fasano, Alfonso, Cereda, Emanuele, Barichella, Michela
|
|
et al. (2020) COVID-19 in Parkinson’s Disease Patients Living in Lombardy, Italy. Movement disorders : official journal of the Movement Disorder Society
|
|
35(7): 1089–1093 [<a href="/pmc/articles/PMC7300944/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7300944</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32484584" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32484584</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>The study included ‘probable’ unconfirmed cases in the analysis, and the analysis is unadjusted</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Faul, J.L., Kerley, C.P., Love, B.
|
|
et al. (2020) Vitamin d deficiency and ards after sars-cov-2 infection. Irish Medical Journal
|
|
113(5): p84 [<a href="https://pubmed.ncbi.nlm.nih.gov/32603575" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32603575</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Galmes, Sebastia; Serra, Francisca; Palou, Andreu (2020) Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework. Nutrients
|
|
12(9) [<a href="/pmc/articles/PMC7551697/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7551697</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32911778" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32911778</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Ecological study using countries’ population mineral intake as parameter, then simple correlation to COVID-19 incidence or death</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Goncalves, T.J.M., Goncalves, S.E.A.B., Guarnieri, A.
|
|
et al. (2020) Prevalence of obesity and hypovitaminosis D in elderly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Nutrition ESPEN [<a href="/pmc/articles/PMC7552968/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7552968</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33183522" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33183522</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Gromova, O. A.; Yu, T. I.; Kh, G. G. (2020) COVID-19 pandemic: Protective role of vitamin D. Farmakoekonomika
|
|
13(2): 132–145
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study not reported in English</p>
|
|
<p>
|
|
<i>Published in Russian</i>
|
|
</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Haj Bloukh, Samir, Edis, Zehra, Shaikh, Annis A
|
|
et al. (2020) A Look Behind the Scenes at COVID-19: National Strategies of Infection Control and Their Impact on Mortality. International journal of environmental research and public health
|
|
17(15) [<a href="/pmc/articles/PMC7432648/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7432648</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32759816" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32759816</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p>
|
|
<i>Narrative review of ecological studies using worldwide geographical distribution of SARS CoV2 from ECDC</i>
|
|
</p>
|
|
<p>- Review article but not a systematic review</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hamza, A., Ahmed, M., Ahmed, K.
|
|
et al. (2020) Role of Vitamin D in Pathogenesis and Severity of Coronavirus Disease 2019 (COVID-19) Infection. Pakistan Journal of Medical and Health Sciences
|
|
14(2): 462–465
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted values</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hribar, Casey A; Cobbold, Peter H; Church, Frank C (2020) Potential Role of Vitamin D in the Elderly to Resist COVID-19 and to Slow Progression of Parkinson’s Disease. Brain sciences
|
|
10(5) [<a href="/pmc/articles/PMC7287983/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7287983</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32397275" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32397275</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Ilie, Petre Cristian; Stefanescu, Simina; Smith, Lee (2020) The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging clinical and experimental research [<a href="/pmc/articles/PMC7202265/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7202265</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32377965" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32377965</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Im, Jae Hyoung, Je, Young Soo, Baek, Jihyeon
|
|
et al. (2020) Nutritional status of patients with COVID-19. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
|
|
100: 390–393 [<a href="/pmc/articles/PMC7418699/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7418699</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32795605" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32795605</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Jovic, Thomas H, Ali, Stephen R, Ibrahim, Nader
|
|
et al. (2020) Could Vitamins Help in the Fight Against COVID-19?. Nutrients
|
|
12(9) [<a href="/pmc/articles/PMC7551685/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7551685</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32842513" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32842513</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Review article but not a systematic review</p>
|
|
<p>- Does not contain a cohort of people and therefore no extractable data</p>
|
|
<p><i>Also included animal studies</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kara, Murat, Ekiz, Timur, Ricci, Vincenzo
|
|
et al. (2020) ‘Scientific Strabismus’ or Two Related Pandemics: COVID-19 & Vitamin D Deficiency. The British journal of nutrition: 1–20 [<a href="/pmc/articles/PMC7300194/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7300194</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32393401" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32393401</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Karonova, T. L.; Andreeva, A. T.; Vashukova, M. A. (2020) serum 25(oH)D level in patients with CoVID-19. Jurnal Infektologii
|
|
12(3): 21–27
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study not reported in English</p>
|
|
<p><i>Reported in Russian. Only abstract in English</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Karonova, T.L., Vashukova, M.A., Gusev, D.A.
|
|
et al. (2020) Vitamin D deficiency as a factor for immunity stimulation and lower risk of acute respiratory infections and COVID-19. Arter. Hypertens. 3(26): 295–303
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study not reported in English</p>
|
|
<p><i>Publication only available in Russian</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Laird, E.; Rhodes, J.; Kenny, R.A. (2020) Vitamin D and inflammation: Potential implications for severity of Covid-19. Irish Medical Journal
|
|
113(5): p81 [<a href="https://pubmed.ncbi.nlm.nih.gov/32603576" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32603576</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Macaya, Fernando, Espejo Paeres, Carolina, Valls, Adrian
|
|
et al. (2020) Interaction between age and vitamin D deficiency in severe COVID-19 infection Interaccion entre la edad y el deficit de vitamina D en la COVID-19 grave. Nutricion hospitalaria [<a href="https://pubmed.ncbi.nlm.nih.gov/32960622" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32960622</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Duplicate reference</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Maghbooli, Zhila, Sahraian, Mohammad Ali, Ebrahimi, Mehdi
|
|
et al. (2020) Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PloS one
|
|
15(9): e0239799 [<a href="/pmc/articles/PMC7518605/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7518605</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32976513" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32976513</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Multivariable analysis was conducted, but only p values were reported. Univariate analyses were reported more fully, but were not adjusted for confounding variables as specified in the protocol</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Mardani, R, Alamdary, A, Mousavi Nasab, S D
|
|
et al. (2020) Association of vitamin D with the modulation of the disease severity in COVID-19. Virus research
|
|
289: 198148 [<a href="/pmc/articles/PMC7455115/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7455115</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32866536" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32866536</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain outcomes of interest</p>
|
|
<p><i>Only reports indirect outcome of interest (simple correlation with ACE level)</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
McKenna, M.J. and Flynn, M.A.T. (2020) Covid-19, cocooning and vitamin d intake requirements. Irish Medical Journal
|
|
113(5): p79 [<a href="https://pubmed.ncbi.nlm.nih.gov/32603573" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32603573</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Not a peer-reviewed publication</p>
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p>- Data not reported in an extractable format</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Munshi, Ruhul, Hussein, Mohammad H, Toraih, Eman A
|
|
et al. (2020) Vitamin D insufficiency as a potential culprit in critical COVID-19 patients. Journal of medical virology
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Systematic review does not meet protocol inclusion criteria, also using flawed statistical analysis (pooling unadjusted data that with severe heterogeneity with I<sup>2</sup> = 99.1%)</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Namayandeh, S. M. (2020) Vitamin D and coronavirus disease (COVID-19);is deficiency and maintenance supplementation therapy necessary?. Journal of Nutrition and Food Security
|
|
5(3): 187–191
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Orru, B, Szekeres-Bartho, J, Bizzarri, M
|
|
et al. (2020) Inhibitory effects of Vitamin D on inflammation and IL-6 release. A further support for COVID-19 management?. European review for medical and pharmacological sciences
|
|
24(15): 8187–8193 [<a href="https://pubmed.ncbi.nlm.nih.gov/32767348" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32767348</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Padhi, S., Suvankar, S., Panda, V.K.
|
|
et al. (2020) Lower levels of vitamin D are associated with SARS-CoV-2 infection and mortality in the Indian population: An observational study. International Immunopharmacology
|
|
88: 107001 [<a href="/pmc/articles/PMC7489890/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7489890</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33182040" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33182040</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unclear where the study obtained the vitamin D status data</i>.</p>
|
|
<p>- Study does not contain outcomes of interest</p>
|
|
<p><i>Study reports simple unadjusted correlation r</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Pereira, Marcos, Dantas Damascena, Alialdo, Galvao Azevedo, Laylla Mirella
|
|
et al. (2020) Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Critical reviews in food science and nutrition: 1–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/34384300" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34384300</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Inappropriate meta-analysis: heterogenous baseline characteristics of index studies, point estimates from index studies some are adjusted (on different variables) and some are unadjusted</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Pizzini, Alex, Aichner, Magdalena, Sahanic, Sabina
|
|
et al. (2020) Impact of Vitamin D Deficiency on COVID-19-A Prospective Analysis from the CovILD Registry. Nutrients
|
|
12(9) [<a href="/pmc/articles/PMC7551662/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7551662</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32932831" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32932831</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unadjusted analysis</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Roselin, C. and Parameshwari, S. (2020) Role of vitamin d in boosting immunity against covid-19. International Journal of Research in Pharmaceutical Sciences
|
|
11(specialissue1): 425–429
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Rozga, Mary, Cheng, Feon W., Moloney, Lisa
|
|
et al. (2020) Effects of Micronutrients or Conditional Amino Acids on COVID-19 Related Outcomes: An Evidence Analysis Center Scoping Review. Journal of the Academy of Nutrition and Dietetics
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Does not contain a population of people with COVID-19</p>
|
|
<p><i>One study was identified that assess the effect of cholecalciferol in patients with ventilator-related pneumonia</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Singh, S K; Jain, Rujul; Singh, Shipra (2020) Vitamin D deficiency in patients with diabetes and COVID- 19 infection. Diabetes & metabolic syndrome
|
|
14(5): 1033–1035 [<a href="/pmc/articles/PMC7332933/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7332933</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32640414" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32640414</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Singh, Samer; Kaur, Rajinder; Singh, Rakesh Kumar (2020) Revisiting the role of vitamin D levels in the prevention of COVID-19 infection and mortality in European countries post infections peak. Aging clinical and experimental research
|
|
32(8): 1609–1612 [<a href="/pmc/articles/PMC7426200/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7426200</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32797388" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32797388</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain any relevant predictive values</p>
|
|
<p><i>Unclear where the study obtained the vitamin D status data, no baseline characteristics data</i>.</p>
|
|
<p>- Study does not contain outcomes of interest</p>
|
|
<p><i>Results presented as simple unadjusted correlation r</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Tan, Si Heng Sharon, Hong, Choon Chiet, Saha, Soura
|
|
et al. (2020) Medications in COVID-19 patients: summarizing the current literature from an orthopaedic perspective. International orthopaedics [<a href="/pmc/articles/PMC7244258/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7244258</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32445030" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32445030</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Data not reported in an extractable format</p>
|
|
<p>- Study does not contain outcomes of interest</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Yalcin Bahat, Pinar, Aldikactioglu Talmac, Merve, Bestel, Aysegul
|
|
et al. (2020) Micronutrients in COVID-19 Positive Pregnancies. Cureus
|
|
12(9): e10609 [<a href="/pmc/articles/PMC7515144/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7515144</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32983745" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32983745</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study does not contain outcomes of interest</p>
|
|
<p><i>Outcomes were blood levels of micronutrients including vitamin D. No correlation between vitamin D status and disease severity or any other outcome relevant to the review protocol was reported</i>.</p>
|
|
<p>- Not a relevant study design</p>
|
|
<p><i>Case series of pregnant women who tested positive for SARS-CoV2 infection and had their blood vitamin D levels measured</i>.</p>
|
|
</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Yilmaz, Kamil and Sen, Velat (2020) Is vitamin D deficiency a risk factor for COVID-19 in children?. Pediatric pulmonology [<a href="/pmc/articles/PMC7675606/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7675606</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33017102" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33017102</span></a>]
|
|
</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Study does not contain any relevant predictive values</p>
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<p><i>Unadjusted analysis</i>.</p>
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</td></tr><tr><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Yousfi, Narimen, Bragazzi, Nicola Luigi, Briki, Walid
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et al. (2020) The COVID-19 pandemic: how to maintain a healthy immune system during the lockdown - a multidisciplinary approach with special focus on athletes. Biology of sport
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37(3): 211–216 [<a href="/pmc/articles/PMC7433333/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7433333</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32879542" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32879542</span></a>]
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</td><td headers="hd_h_niceng187er1.appg.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Review article but not a systematic review</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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