SARS-CoV-2 Reinfection and Risk of Multisystem Inflammatory Syndrome in Children: A Case-Control Study.

BACKGROUND

Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, primarily affecting children aged 6-12 years. Although MIS-C was prominent during the early pandemic waves, recent studies suggest a declining incidence concurrent with increasing reinfection rates. The objective was to determine whether the risk of MIS-C differs following a primary SARS-CoV-2 infection versus reinfection.

METHODS

A retrospective, multicenter, international, matched case-control study was conducted from September 1, 2021, to April 30, 2022. MIS-C cases were recruited from 14 French and Swiss hospitals. Eligible cases included children younger than 18 years meeting the 2020 World Health Organization case MIS-C definition with laboratory evidence of SARS-CoV-2 infection. Cases were matched 1:1 by age, sex and epidemic period to controls with laboratory-confirmed acute SARS-CoV-2 infection. Vaccinated patients and those without consent were excluded. The primary outcome compared the association of reinfection with MIS-C versus acute infection using McNemar's test to estimate matched odds ratios (ORs). Prespecified sensitivity analyses used conditional logistic regression.

RESULTS

The matched cohort included 180 MIS-C cases (median [IQR] age, 106 [62-136] months) and 180 controls (median [interquartile range] age, 72 [48-108] months). No MIS-C cases had a documented reinfection, whereas 3.9% (7/180) of controls did (McNemar χ2 = 5.142; P = 0.023; matched OR, 0.067; 95% confidence interval [0.004-1.167]; P = 0.064). Sensitivity analysis also suggested a lower odds of MIS-C after reinfection without reaching statistical significance (adjusted OR, 0.183; 95% [0.027-1.234]; P = 0.093).

CONCLUSION

MIS-C occurred predominantly after first SARS-CoV-2 infections; while evidence for a lower risk following reinfection was suggestive but not conclusive.