Importance: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited.

Objective: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years.

Design, setting, and participants: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020.

Exposures: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years).

Main outcomes and measures: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections.

Results: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months).

Conclusions and relevance: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.

Dr Randolph reported receiving grants from the Centers for Disease Control and Prevention (CDC) during the conduct of this study and personal fees from UpToDate and serving as a scientific advisor for LaJolla Pharma outside the submitted work. Ms Newhams reported receiving grants from the CDC during the conduct of the study. Ms Bidol reported receiving grants from the CDC during the conduct of the study. Mr Henderson reported receiving grants from the CDC during the conduct of this study. Dr Heidemann reported grants from NIH during the conduct of the study. Dr Singh reported grants from CDC during the conduct of the study. Dr Giuliano reported receiving grants from the CDC during the conduct of the study. Dr Kleinman reported receiving grants from the CDC during the conduct of the study and owning stock in Regeneron, GlaxoSmithKline, Sanofi, Amgen. Dr Tarquinio reported receiving grants from the CDC. Dr Walsh reported receiving grants from the CDC during the conduct of the study. Dr Fitzgerald receiving reported grants from the CDC and National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study. Dr Gertz reported receiving grants from the CDC during the conduct of the study. Dr R. W. Carroll reported receiving personal fees from EDCTP and Unitaid outside the submitted work. Dr Coffin reported receiving grants from and serving on a data and safety monitoring board for Merck & Co. and serving as a consultant for Genentech outside the submitted work. Ms Perella reported receiving grants from the CDC outside the submitted work. Ms Jones reported receiving grants from CDC during the conduct of the study. Dr Flori reported receiving grants from the National Heart, Lung and Blood Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development, serving on committees for the Society for Critical Care Medicine Sepsis, Michigan Thoracic Society, and Pediatric Acute Lung Injury and Sepsis Investigators Network outside the submitted work. Dr N. J. Thomas reported receiving grants from the CDC during the conduct of the study. No other disclosures were reported.