The second wave of children diagnosed with multi-system inflammatory syndrome (MIS-C) experienced more severe illness than the first wave, according to a new study published by doctors at Children’s National Hospital in Washington, D.C. The researchers say this uptick in severity could be due to repeated exposure over time to SARS-CoV-2.
In May 2020, the CDC and WHO released the first official advisories on MIS-C in children, linking it to the emergence and spread of COVID-19. MIS-C is characterized by symptoms similar to those of Kawasaki disease and toxic shock syndrome. The young patients who first presented with the syndrome in the UK had a persistent fever and a constellation of symptoms, including hypotension, multiorgan (e.g., cardiac, gastrointestinal, renal, hematologic, dermatologic and neurologic) involvement, and elevated inflammatory markers.
Children’s National Hospital has seen more than 185 MIS-C patients since the pandemic began. Forty-three children were hospitalized during wave 1 between March and October 2020. Wave 2 occurred about 4 weeks after the largest surge of COVID-19 in the U.S. to date, resulting in 63 children hospitalized between November 2020 and April 2021.
Comparing the 106 patients from both waves, doctors noted that the second wave patients presented with more severe symptoms than the first, although clinical outcomes stayed the same.
According to the study, published in The Pediatric Infectious Disease Journal, patients in wave 2 were more likely to present with shortness of breath—18% compared with just 3% in wave 1—and required more advanced respiratory and inotropic support. Wave 2 patients also required ICU level of care more often than their predecessors—81% compared with 65%.
Additionally, wave 2 patients included a higher proportion of children 15 years of age or (21% vs. 5%), and were less likely to fulfill diagnostic criteria for Kawasaki disease (21% vs. 49%), making clinical diagnosis even more difficult.
Despite the increased degree of clinical severity in the wave 2 cohort, no mortalities occurred and all patients—across the two groups—were discharged at a median of 11 days. Surprisingly, the doctors did not see any significant differences with respect to coronary artery abnormalities between the two groups, either.
In fact, both groups had the same key demographic features—Black (54%) and Latino (39%) children are significantly more affected than white children, and three-quarters of the patents were otherwise healthy with no underlying medical conditions.
So while researchers still do not understand the exact immunologic mechanisms that trigger MIS-C, study co-author Roberta DeBiasi, M.D., has an idea as to why wave 2 patients at the hospital presented with more severe symptoms than wave 1 patients.
“Kids in the second wave cohort had potentially experienced intermittent and/or repeated exposures to the virus circulating in their communities,” said the chief of the Division of Pediatric Infectious Diseases at Children’s National Hospital. “In turn, this may have served as repeated triggers for their immune system, which created the more severe inflammatory response.”
Since the researchers began their study, a third wave of MIS-C patients associated with the surging Delta variant have presented. However, it appears to have affected less children than the previous two waves and is already tapering off.
Still, DeBiasi said she and her team will soon analyze data from the third wave in the hopes of uncovering more insights into the somewhat mysterious MIS-C.
Children’s National Hospital is also working with the National Institute of Allergy and Infectious Diseases (NIAID) to study the long-term effects of MIS-C and COVID-19 on the pediatric population after recovery. The study is among the largest and longest being conducted in connected to the COVID-19 pandemic.