Study provides ‘greater insight’ into MIS-C
Two peaks of multisystem inflammatory syndrome in children — the rare but severe condition associated with SARS-CoV-2 infection — occurred 2 to 5 weeks after peaks of COVID-19 in United States, experts reported in JAMA Pediatrics.
A third peak of the condition known as MIS-C concluded in January and followed another rise in COVID-19 cases in the U.S., according to Ermias D. Belay, MD, one of the multisystem inflammatory syndrome unit leads for the CDC’s COVID-19 Response Team, and colleagues.
Belay and colleagues conducted a cross-sectional analysis of clinical and laboratory data from 1,733 cases of MIS-C to identify clinical characteristics of the syndrome and describe its distribution.
According to the CDC, there have been 3,185 reported cases of MIS-C in the U.S. as of March 29, including 36 deaths. The study included only cases reported up to Jan. 19 of this year.
According to the analysis, there were 2.1 cases of MIS-C per 100,000 children aged younger than 21 years nationally. Cases varied from 0.2 to 6.3 children per 100,000 in states that reported cases of MIS-C, Belay and colleagues reported.
Of the confirmed cases, 57.6% were male and 71.3% were either Hispanic or non-Hispanic Black. The median age of patients was 9 years. Cases were split evenly among males and females in the youngest age group — up to age 4 years — but males outnumbered females by a 2-to-1 ratio among patients aged 18 to 20 years, Belay and colleagues reported.
More than 90% of patients had an illness involving at least four organ systems, 54% had hypotension or shock and around 59% were admitted for intensive care, according to the study.
Cardiac dysfunction was reported in 31% of patients, pericardial effusion in around 23%, myocarditis in around 17%, and coronary artery dilatation or aneurysms in approximately 16%.
Patients aged 0 to 4 years had the lowest proportion of severe manifestations, according to Belay and colleagues, although they found that around 38% experienced hypotension or shock and about 44% were admitted for intensive care.
Myocarditis, pneumonia, acute respiratory distress syndrome and positive PCR tests were most common among patients aged 18 to 20 years, occurring around 31%, 36%, 18% and 71% of the time, respectively.
“The geographic and temporal occurrence of MIS-C in close association with the COVID-19 pandemic and the high proportion of patients with IgG positivity are consistent with earlier hypotheses that the emergence of MIS-C is due to delayed immunologic responses to infection by SARS-CoV-2,” Belay and colleagues wrote.
In a related editorial, Jennifer A. Blumenthal, MD, assistant in critical care medicine at Boston Children’s Hospital, and Jeffrey P. Burns, MD, MPH, chief of the division of critical care medicine at Boston Children’s, called the study “a notable step forward in answering [questions about MIS-C] by providing greater insight into the epidemiology of MIS-C.”
Still, there remain essential gaps in the understanding of MIS-C and its effect on children, they said.
“Given the imprecision of the case definition, more sensitive and specific diagnostic tests are needed to distinguish children with MIS-C from COVID-19 more accurately,” Blumenthal and Burns wrote. “Moreover, further research is needed to assess the most effective and efficient therapies to treat serious and life-threatening presentations and long-term sequelae of MIS-C.”
References:
Belay ED, et al. JAMA Pediatr. 2021;doi:10.1001/jamapediatrics.2021.0630.
Blumenthal JA, et al. JAMA Pediatr. 2021;doi:10.1001/jamapediatrics.2021.0638.
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The study further strengthens the epidemiologic link between COVID-19 infection in children and MIS-C. Previous studies have speculated that MIS-C is a dysregulated immune response with hyperinflammation in response to recent COVID-19 infection, most often seen in the recovery period, when antibody production would peak. The researchers used CDC data to map the geographic spread of reported MIS-C cases over time and align these reports with the known COVID-19 prevalence in the communities. As predicted, reports of MIS-C peak 2 to 5 weeks after spikes in COVID-19 cases. This strengthens the epidemiologic link and provides a warning for areas with increasing prevalence of COVID-19: MIS-C may not be far behind. This warning also provides a baseline for our expectations and may help determine if variants of SARS CoV-2 have the same risk of MIS-C as the previous U.S. strains.
The authors also have generated one of the largest data sets of patients with MIS-C to date. They reaffirm the demographics, significant components of shock and myocardial involvement, and continued low but appreciable mortality rate. Of note, almost double the number of patients with coronary aneurysms were reported compared with previous reviews in the U.S. and United Kingdom. These data will further our understanding of this syndrome.
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