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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2024-08-27T00:00:00-04:00" class="date-display-single">August 27, 2024</span></p><div class='syndicate'><h1>How SARS-CoV-2 might cause dangerous inflammation in children</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Researchers found one way that SARS-CoV-2 infection can lead to a severe complication in children called MIS-C.</li>
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<li>The findings could help shed light on how MIS-C and other autoimmune diseases develop after viral infections.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Sick young girl asleep in a hospital bed.">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/news-releases/2024/20240827-covid-kids.jpg?itok=6RQ3niga&timestamp=1724765344 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/news-releases/2024/20240827-covid-kids.jpg?itok=uaKhA82o&timestamp=1724765344 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/news-releases/2024/20240827-covid-kids.jpg?itok=I-BYIFMJ&timestamp=1724765344 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/news-releases/2024/20240827-covid-kids.jpg?itok=NHZi8sl4&timestamp=1724765344 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/news-releases/2024/20240827-covid-kids.jpg?itok=1XvA26te&timestamp=1724765344 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/news-releases/2024/20240827-covid-kids.jpg?itok=uaKhA82o&timestamp=1724765344" alt="Sick young girl asleep in a hospital bed." title="Sick young girl asleep in a hospital bed." />
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</picture><span class="caption">The study yielded insights into development of the rare, life-threatening complication called multisystem inflammatory syndrome in children, or MIS-C. </span><span class="credit">Kunlanan Yarist / Shutterstock</span></div>
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</div><p>Children infected with SARS-CoV-2, the virus that causes COVID-19, can develop a rare, life-threatening complication called multisystem inflammatory syndrome in children (MIS-C). In MIS‑C, aberrant immune responses cause inflammation throughout the body. But it’s not clear how SARS-CoV-2 infection leads to MIS-C. </p>
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||
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||
<p>To gain more insight, a team of researchers led by Drs. Aaron Bodansky, Mark Anderson and Joseph DeRisi at the University of California, San Francisco compared blood samples from almost 200 children with MIS-C to 45 control children without MIS-C. All had recent SARS-CoV-2 infections. Results of the study, which was partially funded by NIH, appeared in <em>Nature </em>on August 7, 2024.</p>
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||
<p>The team looked at whether the two groups had different antibodies targeting human proteins. They found that MIS-C patients had antibodies to a distinct set of proteins. One of these was SNX8, which is found at high levels within immune cells. SNX8 is involved in a virus defense pathway that has been implicated in MIS-C. Almost all the antibodies against SNX8 from MIS-C patients recognized the same structural feature on the protein.</p>
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||
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||
<p>The researchers also examined antibody responses to SARS-CoV-2 proteins. They found that MIS-C patients produced a lot more antibodies that targeted a specific site on the viral nucleocapsid protein. This site closely resembles the site on the SNX8 protein that the patients’ antibodies recognized. Because of this molecular mimicry, the same antibodies targeting the viral nucleocapsid may be recognizing the body’s SNX8 protein.</p>
|
||
|
||
<p>As antibodies can’t access proteins inside of cells, the team then looked for T cells that reacted to SNX8. They found them in MIS-C patients but not in controls. These T cells recognized both the site on SNX8 and the site on the nucleocapsid protein that the antibodies recognized.</p>
|
||
|
||
<p>The findings provide a plausible mechanism by which SARS-CoV-2 infection can, in rare cases, lead to MIS-C. First, the immune system reacts to a specific site on the viral nucleocapsid protein. Then, because this site so closely resembles part of SNX8, the immune system begins to mistakenly target the body’s own SNX8 protein.</p>
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||
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||
<p>Viral infections are also believed to trigger other autoimmune diseases, such as type 1 diabetes and multiple sclerosis. The findings could help in understanding and eventually treating these conditions as well.</p>
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||
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<p>“We hope this kind of approach can help break new ground in understanding similar diseases of immune dysregulation that have stumped us for decades,” Bodansky says.</p>
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<p>—by Brian Doctrow, Ph.D.</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/how-sars-cov-2-contributes-heart-attacks-strokes" target="_top">How SARS-Cov-2 Contributes to Heart Attacks and Strokes</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/long-covid-symptoms-linked-inflammation" target="_top">Long COVID Symptoms Linked to Inflammation</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/study-suggests-epstein-barr-virus-may-cause-multiple-sclerosis" target="_top">Study Suggests Epstein-Barr Virus May Cause Multiple Sclerosis</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/misdirected-antibodies-linked-severe-covid-19" target="_top">Misdirected Antibodies Linked to Severe COVID-19</a></li><li><a href="https://newsinhealth.nih.gov/2022/06/understanding-autoimmune-diseases" target="_top">Understanding Autoimmune Diseases: When Your Body Turns Against You</a></li><li><a href="https://www.niaid.nih.gov/diseases-conditions/long-covid-multisystem-inflammatory-syndrome-children-misc" target="_top">Long COVID and Multisystem Inflammatory Syndrome in Children (MIS-C)</a></li><li><a href="https://www.niams.nih.gov/health-topics/autoinflammatory-diseases" target="_top">Autoinflammatory Diseases</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/39112696/">Molecular mimicry in multisystem inflammatory syndrome in children.</a> Bodansky A, Mettelman RC, Sabatino JJ Jr, Vazquez SE, Chou J, Novak T, Moffitt KL, Miller HS, Kung AF, Rackaityte E, Zamecnik CR, Rajan JV, Kortbawi H, Mandel-Brehm C, Mitchell A, Wang CY, Saxena A, Zorn K, Yu DJL, Pogorelyy MV, Awad W, Kirk AM, Asaki J, Pluvinage JV, Wilson MR, Zambrano LD, Campbell AP; Overcoming COVID-19 Network Investigators; Thomas PG, Randolph AG, Anderson MS, DeRisi JL. <em>Nature</em>. 2024 Aug;632(8025):622-629. doi: 10.1038/s41586-024-07722-4. Epub 2024 Aug 7. PMID: 39112696.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Centers for Disease Control and Prevention; Chan Zuckerberg Biohub; Boston Children’s Hospital; American Lebanese Syrian Associated Charities.</p>
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<p><strong>Mailing Address:</strong><br />
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NIH Research Matters<br />
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Bldg. 31, Rm. 5B52, MSC 2094<br />
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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