ABSTRACT
Background. Risk factors for MIS-C, a rare but serious hyperinflammatory syndrome associated with SARS-CoV-2 infection, remain unclear. We evaluated household, clinical, and environmental risk factors potentially associated with MIS-C. Methods. This investigation included MIS-C cases hospitalized in 14 US pediatric hospitals in 2021. Outpatient controls were frequency-matched to case-patients by age group and site and had a positive SARS-CoV-2 viral test within 3 months of the admission of their matched MIS-C case (Figure 1). We conducted telephone surveys with caregivers and evaluated potential risk factors using mixed effects multivariable logistic regression, including site as a random effect. We queried regarding exposures within the month before hospitalization for MIS-C cases or the month after a positive COVID-19 test for controls. Enrollment scheme for MIS-C case-patients and SARS-CoV-2-positive outpatient controls. MIS-C case-patients were identified through hospital electronic medical records, while two outpatient controls per case were identified through registries of outpatient SARS-CoV-2 testing logs at facilities affiliated with that medical center. Caregivers of outpatient controls were interviewed at least four weeks after their positive test to ensure they did not develop MIS-C after their infection. Results. We compared 275 MIS-C case-patients with 494 outpatient SARS-CoV-2-positive controls. Race, ethnicity and social vulnerability indices were similar. MIS-C was more likely among persons who resided in households with >1 resident per room (aOR=1.6, 95% CI: 1.1-2.2), attended a large (>=10 people) event with little to no mask-wearing (aOR=2.2, 95% CI: 1.4-3.5), used public transportation (aOR=1.6, 95% CI: 1.2-2.1), attended school >2 days per week with little to no mask wearing (aOR=2.1, 95% CI: 1.0-4.4), or had a household member test positive for COVID-19 (aOR=2.1, 95% CI: 1.3-3.3). MIS-C was less likely among children with comorbidities (aOR=0.5, 95% CI: 0.3-0.9) and in those who had >1 positive SARS-CoV-2 test at least 1 month apart (aOR=0.4, 95% CI: 0.2-0.6). MIS-C was not associated with a medical history of recurrent infections or family history of underlying rheumatologic disease. Conclusion. Household crowding, limited masking at large indoor events or schools and use of public transportation were associated with increased likelihood of developing MIS-C after SARS-CoV-2 infection. In contrast, decreased likelihood of MIS-C was associated with having >1 SARS-CoV-2 positive test separated by at least a month. Our data suggest that additional studies are needed to determine if viral load, and/or recurrent infections in the month prior to MIS-C contribute to MIS-C risk. Medical and family history were not associated with MIS-C in our analysis.