Early in the COVID-19 pandemic, some children fought off the virus with few, if any, symptoms, only to suffer severe organ failure weeks later.
This sudden illness, called multisystem inflammatory syndrome in children (MIS-C), puzzled doctors. Most kids recovered after intensive treatment, but the cause remained a mystery.
Now, scientists from UC San Francisco, Chan Zuckerberg Biohub San Francisco, St. Jude Children’s Research Hospital, and Boston Children’s Hospital have discovered the cause of many MIS-C cases.
Their findings could also help understand other autoimmune diseases.
The researchers found that in many children, the immune system mistakenly attacked their own tissues after fighting off COVID-19.
The immune system targeted a part of the coronavirus that closely resembles a protein found in various body parts, such as the heart, lungs, kidneys, brain, skin, eyes, and GI tract. This triggered a massive immune response, causing severe illness.
Published in Nature, this study offers one of the clearest connections yet between viral infections and subsequent autoimmune diseases.
“Thanks to our world-class team, we’ve found an answer for how children get this mysterious disease,” said Aaron Bodansky, MD, the lead author and a critical care fellow at UCSF.
COVID’s unexpected impact on kids
As COVID-19 spread, MIS-C cases appeared, affecting about one in 2,000 children under 18 who contracted the virus.
Adrienne Randolph, MD, a critical care pediatrician at Boston Children’s Hospital, tracked these cases and collected patient samples through a national network of pediatric ICUs.
“Every time COVID peaked in an area, about 30 days later, there’d be a peak of these kids presenting with what looked like septic shock,” Randolph said. “If we hadn’t intervened and supported them, they could have died.”
Bodansky noticed that MIS-C resembled other rare pediatric inflammatory diseases, such as Kawasaki disease.
Co-senior author Mark Anderson, MD, suggested using a tool called Phage Immunoprecipitation Sequencing (PhIP-Seq) to investigate further. PhIP-Seq screens blood for autoantibodies, which are antibodies that mistakenly attack the body instead of a virus.
With the CDC’s approval, Randolph sent samples from 199 children with MIS-C to UCSF, along with 45 samples from children who had COVID but did not develop MIS-C.
The researchers discovered that one-third of the MIS-C cases had autoantibodies targeting a human protein called SNX8. These autoantibodies were also attacking a part of the coronavirus protein that closely resembled SNX8.
The team suspected that killer T cells, which destroy infected cells, were also involved. Joe Sabatino, MD, PhD, and Paul Thomas, PhD, found that some T cells from MIS-C patients targeted both SNX8 and the coronavirus protein. This confirmed the autoimmune reaction.
Most children who had MIS-C have fully recovered, and new cases are now rare, mostly appearing in unvaccinated children.
By tracing MIS-C from virus to autoantibody to T cell, the study offers a new way to investigate and potentially treat autoimmune diseases.
“This paper is special because it actually finds the smoking gun—what made these kids so sick,” said Joe DeRisi, PhD, a co-senior author. “It opens the door to understanding why so many post-infectious, horribly inflammatory autoimmune events occur.”
In summary, this research not only solves a key mystery of the COVID-19 pandemic but also provides hope for better understanding and treatment of autoimmune diseases in the future.
If you care about COVID, please read studies about vitamin D deficiency linked to severe COVID-19, death, and how diets could help manage post-COVID syndrome.
For more health information, please see recent studies about COVID infection and vaccination linked to heart disease, and results showing extracts from two wild plants can inhibit COVID-19 virus.
