What Causes the Rare COVID-19 Response in Children?

COVID-19 in children
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A Yale-led study has shed light on the rare COVID-19 response in children that often results in a life-threatening inflammatory condition.

Luckily, COVID-19 has largely spared children. Most either remain asymptomatic or develop a mild infection. But some can develop a rare life-threatening condition called multi-system inflammatory syndrome in children (MIS-C). Cases of the illness first appeared in April of last year. At the time, it was compared with Kawasaki disease and Toxic Shock Syndrome due to similar symptoms. However, doctors soon came to refer to it as MIS-C. The illness usually begins 4-6 weeks after infection with the novel coronavirus. But what’s causing the discrepancy in the COVID-19 response in children? Why do some develop a mild infection and others MIS-C? A Yale-led study may have finally found some answers to these questions.

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, study author

The incidence of MIS-C is about one in a thousand. It mostly presents in older children belonging to the Black and Hispanic/Latino population. Moreover, children across America and Europe have mostly shown signs of the disease. Symptoms include fever, rash, abdominal pain, cardiac involvement, and neurological problems. It also frequently leads to shock and ICU admission in children. Although the condition is treatable, delayed treatment can cause fatalities.

Therefore, the team of researchers conducted a study examining blood samples from children with MIS-C, healthy children, adults with severe COVID-19, and healthy adults. Using a wide range of tests, they identified a significant difference in the immune system of children with MIS-C as compared to other groups. The researchers published their findings in the journal Immunity.

An Overactive Immune System

The results of the study showed a stronger innate immune system in children as compared to adults. Thus, accounting for the milder and asymptomatic infections in children.

The innate immune system is responsible for fighting off pathogens. The entry of foreign antigens into the body activates the quick response. White blood cells form the main army of defenders responsible for keeping infections at bay.

Researchers also found high levels of alarmins in the blood of children with MIS-C. Alarmins are released from infected cells and enhance the innate immune response. Therefore, suggesting a likely cause for the rare COVID-19 response in children.

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.

Carrie Lucas, study author

Furthermore, they also observed elevated adaptive immune responses in the children diagnosed with MIS-C. Adaptive immunity is a slower response, as compared to innate immunity, and its cells rely on immunological memory. Researchers believe that an enhanced adaptive immunity likely leads to an attack on host tissues. The damaged tissue then becomes more susceptible to an attack by the autoantibodies. Thus, resulting in the inflammatory condition.

In conclusion, the immune system signatures identified by researchers can help predict severity and diagnose MIS-C in clinical settings.


Ramaswamy, Anjali, et al. “Immune Dysregulation and Autoreactivity Correlate with Disease Severity in SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children.” Immunity, vol. 54, no. 5, 2021, doi:10.1016/j.immuni.2021.04.003.


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