image of lungs with SARS-CoV-2 particles on them to indicate infection and lung damage from COVID-19
Credit: Peter Zelei Images / Getty Images

Using next generation sequencing, researchers have found biomarkers of multisystem inflammatory syndrome (MIS-C)—a rare condition in children and adolescents linked with the virus that causes COVID-19. These markers are biochemical indicators of cell injury and cell death. They signal damage to multiple organs, the lining of blood vessels, and the nervous system.

The senior author was Charles Y. Chiu, MD, of the University of California, San Francisco, and the study appear this month in Cell Reports Medicine.

In April of 2020, reports from the United Kingdom described a syndrome in children similar to Kawasaki disease (KD) or toxic shock syndrome that appeared to be a rare complication of COVID-19. Since then, similarly affected children and adolescents were reported in other parts of the world. The overlap with KD and toxic shock syndrome have made the condition difficult to diagnose.

It’s also unclear why some patients develop this syndrome and others don’t. There is no evidence yet, for example, that particular variants or pre-existing conditions increase a child’s risk of MIS-C.

It’s estimated that one is 3,000 to 4,000 children and adolescents who have had SARS-CoV-2 infection developed MIS-C. The condition usually arises two to six weeks after the SARS-CoV-2 infection, and may be so mild that it is unrecognized at first. Symptoms can include fever, abdominal pain, vomiting, diarrhea, rash, conjunctivitis, and hypotension. It can also cause inflammation of the heart, lungs, kidneys, brain, skin, eyes or gastrointestinal tract.

Patients with MIS-C show an increase in the level of at least four inflammatory markers (C-reactive protein, neutrophil count, ferritin, procalcitonin, fibrinogen, interleukin-6, and triglycerides).

Early in the pandemic, a team of researchers mapped the immune response in children with MIS-C. They found that, although MIS-C shares some features with KD, the inflammatory response differs from both KD and severe acute COVID-19. That team observed differential frequency of specific immune cell populations, inflammatory cytokines, and chemokines in the blood.

For this study from Chiu’s team, researchers used next-generation sequencing to analyze blood samples from pediatric patients with acute COVID-19 (n=70) or with MIS-C (n=141) from three hospitals.

They write: “Whole blood RNA profiling reveals upregulation of similar pro-inflammatory pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state.”

The team believe their findings could lead to the development of tests that allow clinicians to distinguish between MIS-C and other conditions involving widespread inflammation, such as KD and toxic shock syndrome. They also believe it could help in the development of more appropriate treatments for each.

The authors point out that a recent analysis of COVID-19 vaccination following MIS-C found that there were no reports of serious complications, including myocarditis or MIS-C recurrences after the injection. Suggesting “Everyone should stay up to date with COVID-19 vaccines for their age group, as the U.S. Centers for Disease Control and Prevention recommends, regardless of whether they have been infected with the virus.”

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