Investigators at Cedars-Sinai have proposed a theory for howSARS-CoV-2, the virus that causes COVID-19, infects the body. Their hypothesis,published inFrontiers in Immunology, could explain why some people still have symptoms long after the initial infection.
Weve put together different pieces of datato create a bigger picture that may explain what causes some peoples immune systems to go haywire, leading to post-acute syndromes, includingmultisystem inflammatory syndrome in children(MIS-C)and long COVID in children and adults, saidMoshe Arditi, MD,executive vice chair of the Department of Pediatrics for Research,part of Cedars-Sinai Guerin Childrens,and senior author of the paper.
MIS-C is a rare but dangerous condition in children that may occur weeks after infection with SARS-CoV-2.Long COVID-19often referred to as long COVIDis a termused to describe a constellation of health problems that some people experience as a result of their infection withSARS-CoV-2. Symptoms can last months or even years.
SARS-CoV-2 is thought to latch on to cells via spikes that exist on the surface of the virus. These spike proteins are comprised of molecular motifs,stretches of amino acids that make a protein. These tiny molecular motifs may have what the scientists call superantigen characteristics, meaning that the immune system can overreact to their presence.
The spike protein, according to the authors, may also have neurotoxic motifs that can cross the blood-brain barrier and damage brain cells. This hypothesis could explain the brain fog and other neurological symptoms associated with COVID-19 and long COVID.
The hypothesis is based on several published studies on COVID-19 and other diseases caused by viruses. One such study by Arditi and his longtime collaboratorIvet Bahar, PhD,was publishedin theProceedings of the National Academy of Sciencesin 2020. Bahar and Arditi created a computer model showing how molecular motifs onthe spike protein interact with immune cells. The superantigen molecular motifs cause the immune cells to release an abundance ofinfection-fighting proteins known as cytokinesthat fight the virus but alsomay mistakenly attack the bodys organs. In children, this may manifest as MIS-C.
Other studies have reported that people with long COVID may carry fragments of the virus in their gut or other parts of their bodies months after initial infection. Continuous exposure to motifs that lodge themselves in different parts of the body and have superantigen-like properties may cause autoimmune symptoms in people with long COVID and MIS-C, according to the authors.
We need to conduct more research to prove if this is indeed the mechanism that causes long COVID so that we can develop treatments to block it,saidMagali Noval Rivas, PhD,an investigator at Cedars-Sinai and first author of the paper.
Arditi,theGUESS?/Fashion Industries Guild Chair in Community Child Healthat Cedars-Sinai who leads theInfectious and Immunologic Diseases Research Center,and colleagues are currently conducting a study in which they are analyzing cerebral spinal fluid samples from people with long COVID symptoms for evidence of neurotoxic motifs.
Rebecca A. Porritt, PhD, assistant professor in the departments of Pediatrics and Biomedical Sciences at Cedars-Sinai, also contributed to this work.
Funding: The study was funded by the National Institutes of Health (award numbersR01AI072726, R01AI072726-10S, GM103712, R01GM139297, R01HL139766 and R01HL159297) the American Heart Association (Career Development Award AHA 20CDA35260258), and the Cedars-Sinai Precision Health Award.
Frontiers in Immunology
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Hyperactivation of the immune system may cause post-COVID syndromes - EurekAlert
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