Though most COVID-19 infections in kids are mild, a rare severe illness following infection affects as many as 1 in 2,000 children, called multisystem inflammatory syndrome in children (MIS-C). The disease is characterized by several sudden, significant signs of multi-organ inflammation, including fever, skin rashes, diarrhea, rapid heartbeat, and swelling of the hands and feet.
Now scientists from the University of San Francisco, Chan Zuckerberg Biohub San Francisco, St. Jude Children’s Research Hospital, and Boston Children's Hospital, have published in Nature new research describing the mechanism behind MIS-C, and suggest the findings could have implications for other autoimmune diseases.
First observed in the early months of the pandemic, MIS-C left children with organ failure just weeks after reporting a mild illness with COVID-19. Clinicians noted similarities between Kawasaki disease and other inflammatory conditions in these children, but the cause of the condition was a mystery.
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 in our network of 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 in our network of ICUs, except they were negative for all kinds of infection," said study author Adrienne Randolph, MD, MSc, a critical care pediatrician at Boston Children's Hospital in a press release.
MIS-C becoming more rare each year
In the present study, researchers used blood samples gathered across the United States at pediatric intensive care units, then compared 199 children with MIS-C to 45 samples from children who had not developed MIS-C after COVID.
They found one-third of kids with MIS-C had autoantibodies for a human protein called SNX8, which resembled a portion of SARS-CoV-2's N protein. That autoantibody then influenced T cell response. The interplay means children who develop MIS-C have a strong and dangerous antibody response to the SARS-CoV-2 nucleocapsid protein.
"Thanks to our world-class team we’ve found an answer for how children get this mysterious disease," said Aaron Bodansky, MD, a critical care fellow in UCSF's department of pediatrics and lead author of the paper. "We hope this kind of approach can help break new ground in understanding similar diseases of immune dysregulation that have stumped us for decades, like multiple sclerosis or type 1 diabetes."
The authors concluded their study by noting that MIS-C is becoming more and more rare as COVID-19 becomes endemic, as an increasing number of children have developed immunity through vaccination and natural SARS-CoV-2 infection.
As of July 2, the Centers for Disease Control and Prevention said the United States had recorded 9,698 MIS-C cases since March of 2020, including 79 deaths. Most children with the disorder can expect full recovery.
"Supporting this notion is recent CDC surveillance, which noted that more than 80% (92 of 112) of individuals with MIS-C in 2023 were in unvaccinated children (but vaccine eligible), and that the majority of children who developed MIS-C despite previous vaccination probably had waned immunity," the authors concluded.
