Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation

Abstract

Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC).

Methods: In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data.

Findings: Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals.

Interpretation: Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted.

Funding: US Centers for Disease Control and Prevention.

Figure

Investigation of potential MIS-C in individuals who had received a COVID-19 vaccine CDC=US Centers for Disease Control and Prevention. CISA=Clinical Immunization Safety Assessment. MIS-C=multisystem inflammatory syndrome in children. NAAT=nucleic acid amplification test. VAERS=Vaccine Adverse Event Reporting System. *If the individuals were the incorrect age or if MIS-C could be clearly ruled out on the basis of the VAERS report. †Two individuals were reported to MIS-C national surveillance but not to VAERS, and medical records were not obtained; both had reported MIS-C after one dose of COVID-19 vaccine, and both were positive for SARS-CoV-2 NAAT and IgG, but no further details were available; both clinically improved and were discharged home. ‡Defined as an illness meeting the CDC MIS-C clinical and inflammatory criteria with a positive NAAT or viral antigen test during or before MIS-C illness evaluation, or a positive anti-nucleocapsid antibody test during MIS-C illness evaluation. §Defined as an illness meeting the CDC MIS-C clinical and inflammatory criteria with negative NAAT and anti-nucleocapsid antibody tests and a positive anti-spike antibody test during MIS-C illness evaluation, with no known history of a positive SARS-CoV-2 test before MIS-C illness onset. ¶Three individuals with an illness after vaccination meeting the CDC MIS-C clinical and inflammatory criteria, a negative anti-nucleocapsid antibody test and negative NAAT test during MIS-C evaluation, and anti-spike antibody test not obtained.