Hyperactivation of the immune system can cause post-COVID syndromes

Investigators at Cedars-Sinai have proposed a theory about how SARS-CoV-2, the virus that causes COVID-19, infects the body. Their hypothesis, published in Limits in Immunologycould explain why some people still have symptoms long after the initial infection.

“We have put together different data to create a larger picture that can explain what causes some people’s immune systems to malfunction, leading to post-acute syndromes, including polysystemic inflammatory syndrome in children (MIS-C) and long-term COVID in. children and adults, ”he said Moshe Arditi, MD, executive vice president of the Department of Pediatrics for Research, part of Cedars-Sinai Guerin Children’s, and senior author of the paper.

MIS-C is a rare but dangerous condition in children that can occur weeks after infection with SARS-CoV-2. Long COVID-19 – often called long COVID – is a term used to describe a constellation of health problems that some people experience as a result of their infection with SARS-CoV-2. Symptoms can last for months or even years.

SARS-CoV-2 is thought to attach to cells by stings that exist on the surface of the virus. These pike proteins consist of molecular motifs, pieces of amino acids that make up a protein. These tiny molecular motifs may have what scientists call “superantigenic” characteristics, meaning that the immune system may overreact to its presence.

The pike protein, according to the authors, can 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-term 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 collaborator Ivet Bahar, PhD, was published in the Proceedings of the National Academy of Sciences in 2020. Bahar and Arditi created a computer model showing how molecular motifs on the pike protein interact with immune cells. The superantigenic molecular motives cause the immune cells to release an abundance of infection-fighting proteins known as cytokines that fight the virus but can also erroneously attack the body’s organs. In children, this may manifest as MIS-C.

Other studies have reported that people with long-term COVID can carry fragments of the virus in their gut or other parts of their body months after an initial infection. Prolonged exposure to motifs that reside in different parts of the body and have superantigen-like properties can cause autoimmune symptoms in people with long-term COVID and MIS-C, according to the authors.

“We need to do more research to demonstrate whether this is actually the mechanism that causes long-term COVID so that we can develop treatments to block it,” he said. Magali Noval Rivas, PhD, investigator at Cedars-Sinai and first author of the paper.

Arditi, the GUESS? / Fashion Industries Guild Chair in Community Child Health at Cedars-Sinai who leads the Research Center for Infectious and Immunological Diseasesand colleagues are currently conducting a study in which they analyze samples of brain fluids from people with long-term COVID symptoms for tests of neurotoxic motives.

Rebecca A. Porritt, PhD, assistant professor in the departments of Pediatrics and Biomedical Sciences at Cedars-Sinai, also contributed to that work.

Funding: The study was funded by the National Institutes of Health (award numbers R01AI072726, R01AI072726-10S, GM103712, R01GM139297, R01HL139766 and R01HL159297) the American Heart Association (AHA5272726-105).

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