A few weeks later, around one in 10,000 children with Covid-19 develops a severe inflammatory reaction that affects many organs and can be fatal. According to the results of the latest research, it is likely that this MIS-C or PIMS syndrome is based on genetic mutations in the innate immune system. This was reported by American scientists in the scientific journal “Science”.
Children usually do not get sick with severe courses of SARS-CoV-2 infection. But no matter what symptoms you’ve survived, MIS-C can develop around four weeks after the acute phase of the illness – with acute fever, rashes, abdominal pain, myocarditis, swollen lymph nodes and even vascular changes in the coronary arteries. from the heart, as Deutsches Ärzteblatt reported online on Tuesday. The syndrome is apparently based on an excessive inflammatory reaction in small and medium-sized blood vessels and can affect practically the entire body.
“The umbrella term MIS-C stands for a multi-inflammatory syndrome in children that can occur after a Covid infection,” explained Klaus Kapelari, senior physician at Innsbruck Pediatrics (university clinic) in early 2022. “The cause of the inflammatory processes is probably an exaggerated reaction of the immune system to persistent components of the virus. The number of patients attributed to this syndrome is increasing with each wave”, says the specialist. Those affected need intensive medical care.
In the US, 71 of approximately 9,000 children have died with MIS-C, which resembles the long-known so-called Kawasaki syndrome in children. On the other hand, infections already overcome and a subsequent excessive immune reaction have always been considered as disease-causing processes. How this works, however, was not known until now.
Robert Silverman of the Cleveland Clinic (Ohio/USA) and Jean-Laurent Casanova (Rockefeller University/New York) and their teams were able for the first time to identify genetic factors that apparently promote the development of MIS-C in children (Science; DOI: 10.1126/ science.abo3627). They are likely to be at the genetic level, at least not in relation to viral load strength during infection.
Researchers found what they were looking for in five tiny MIS-C patients
As part of the “Covid Human Genetic Effort”, scientists sequenced the genome or proteins produced in the cells of 558 children who had MIS-C. The data were compared with children who survived Covid-19 and subsequently did not develop this multi-inflammatory syndrome. They first found what they were looking for in five tiny MIS-C patients: They had mutations in the OAS or RNase L protein genes.
“Production of OAS proteins is promoted by interferons as a first line of defense against viral infections. When they ‘sniff’ double-stranded RNA, these OAS proteins activate the RNase L enzyme. spread of the virus,” the Cleveland Clinic and Rockefeller University wrote in a press release (Dec.
Illustrating the effect of mutations that contribute to the development of MIS-C in some children, Silverman said, “RNase L works like scissors, cutting RNA, which is translated into proteins. This includes proteins known as cytokines (immune messengers; note) trigger inflammatory reactions.” Mutations in the genes for OAS proteins or the RNase L enzyme identified as part of the project are likely to have a twofold detrimental effect: like OAS mutations, they either prevent the RNA scissors from functioning or cause this enzyme to function at all. mutations in the RNase L gene).
The result is likely to be a strong inflammatory reaction mediated by immune cells (monocytes and macrophages). As a result, the components of SARS-CoV-2 – even weeks after the acute illness and after the danger has ended – are presented to so-called T cells as “foreign”. T cells eventually attack “wild” tissues.
“The T cells are then, as Silverman suspects, responsible for the inflammatory attacks on the blood vessels, which are presumably behind MIS-C and Kawasaki syndrome. As the acquired immune system only becomes active with a time delay , this would explain why children only develop MIS-C weeks after infection,” writes Deutsches Ärzteblatt.