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Children With MIS-C Show Unique Immune System Signatures

Children who experienced MIS-C showed an elevation of certain adaptive immune responses that confer immunological memory.

A recent analysis conducted by investigators from Yale University has discovered that children who are infected with COVID-19 and experience multi-system inflammatory response (MIS-C) have immune system signatures that are distinct from other groups.

Results from the analysis were published in the journal Immunity.

"Why does this happen when there is no virus or anti-viral response still present and in kids? And why is it only occurring in youth?" Carrie Lucas, a corresponding author of the new study said. "Innate immunity may be more active in children who are infected with the virus, but on the flip side, in rare cases it may get too revved up and contribute to this inflammatory disease."

For the analysis, the team of investigators tested blood samples using single-cell RNA sequencing, flow cytometry, antigen receptor repertoire analysis, and unbiased serum proteomics from children who experienced MIS-C, adults with a severe case of COVID-19, and healthy children and adults.

Results from the analysis showed that the children who experienced MIS-C had higher levels of molecules that make up part of the innate immune system, called alarmins, than the other groups.

Additionally, the children with MIS-C showed an elevation of certain adaptive immune responses that confer immunological memory. Typically, these responses protect against a viral attack but in the children they attacked several of the host tissue.

The investigators believe that the initial immune response may trigger responses that damage healthy tissue which may make them more susceptible to an attack by autoantibodies.

“With new waves of SARS-CoV-2 outbreaks on the horizon and eventual vaccination to protect children from SARS-CoV-2-related disease as a critical goal, a better understanding of MIS-C drivers and immunopathology is urgently needed,” the authors wrote. “Our data implicate innate and adaptive immune triggering with direct relevance for tissue destruction during acute MIS-C.”