Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) Aged 12–20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021

Abstract

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12–20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC.MethodsWe investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC’s health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC’s Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination.FindingsWe identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12–20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12–20 years had received ≥1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1·0 case per million persons receiving ≥1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated persons.InterpretationIn our case series, we describe a small number of persons with MIS-C who had received ≥1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted.FundingThis work was supported by the Centers for Disease Control and Prevention Clinical Immunization Safety Assessment (CISA] Project contracts 200-2012-50430-0005 to Vanderbilt University Medical Center and 200-2012-53661 to Cincinnati Children’s Hospital Medical Center.Research in context panelEvidence before this studyMultisystem inflammatory syndrome in children (MIS-C), also known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is an uncommon, but serious, complication described after SARS-CoV-2 infection that is characterized by a generalized hyperinflammatory response. A review of the literature using PubMed identified reports of six persons aged 12–20 years who developed MIS-C following COVID-19 vaccination. Search terms used to identify these reports were: “multisystem inflammatory syndrome in children”, “MIS-C”, “MISC”, “multisystem inflammatory syndrome in adults”, “MIS-A”, “MISA”, “paediatric inflammatory multisystem syndrome”, and “PIMS-TS” each with any COVID-19 vaccine type. There were no exclusion criteria (i.e., all ages and languages).Added value of this studyWe conducted integrated surveillance for MIS-C after COVID-19 vaccination using two passive surveillance systems, CDC’s MIS-C national surveillance and the Vaccine Adverse Event Reporting System (VAERS), and clinician or health department outreach to CDC, including through Clinical Immunization Safety Assessment (CISA) Project consultations. We investigated reports of potential MIS-C occurring from December 14, 2020, to August 31, 2021, in persons aged 12–20 years any time after receipt of COVID-19 vaccine to identify those that met the CDC MIS-C case definition. Any positive serology test was accepted as meeting the CDC MIS-C case definition, although anti- nucleocapsid antibody is indicative of SARS-CoV-2 infection, while anti-spike protein antibody may be induced either by SARS-CoV-2 infection or by COVID-19 vaccination. We investigated 47 reports and identified 21 persons with MIS-C after receipt of COVID-19 vaccine. Of the 21 persons with MIS-C, median age was 16 years (range 12–20 years), and 13 (62%) were male. Fifteen (71%) had laboratory evidence of past or recent SARS-CoV-2 infection (positive SARS-CoV-2 nucleic acid amplification test [NAAT], viral antigen, or serology test before or during MIS-C illness evaluation), and 5 (33%) of those 15 had illness onset after their second vaccine dose. Six (29%) of 21 persons had no laboratory evidence of past or recent SARS-CoV-2 infection, and five of those six (83%) had onset of MIS-C after the second vaccine dose.Implications of all the available evidenceDuring the first nine months of the COVID-19 vaccination program in the United States, >21 million persons aged 12 to 20 years received ≥1 dose of COVID-19 vaccine as of August 31, 2021. This case series describes MIS-C in 21 persons following vaccine receipt during this time period; the majority of persons reported also had evidence of SARS-CoV-2 infection. The surveillance has limitations, but our findings suggest that MIS-C as identified in this report following COVID-19 vaccination is rare. In evaluating persons with a clinical presentation consistent with MIS-C after COVID-19 vaccination it is important to consider alternative diagnoses, and anti-nucleocapsid antibody testing may be helpful. Continued surveillance for MIS-C illness after COVID-19 vaccination is warranted, especially as pediatric COVID-19 vaccination expands. Providers are encouraged to report potential MIS-C cases after COVID-19 vaccination to VAERS.

Multisystem inflammatory syndrome in children (MIS-C) possibly secondary to COVID-19 mRNA vaccination

“…Yousaf et al recently reported 21 individuals ages 21 and younger with MIS-C following SARS-CoV-2 mRNA vaccination, 6 of whom had no prior evidence of COVID-19 infection. 23 …”

“…This is greater than the original definition of MIS-C per CDC criteria, but it is within the range per WHO and the Brighton Collaborative Case Definition. 10 13 MIS-C cases with longer latency periods up to 16 weeks have been reported in the literature and it is possible that the original time frame of 4–6 weeks is too strict to encompass all cases of MIS-C. 23 24 …”

“… 19 It is possible that the aetiology of postvaccination MIS-C in patients without prior COVID-19 infection may be due to an underlying inflammatory condition that has not been previously identified. 23 …”

SARS-CoV-2 infections and MIS-C among children: A narrative review

“…[20] The following researches show that there are many different reported MIS-C cases and results in kids (Table 2). [18,[20][21][22][23][24][25][26][27]…”

Cutaneous vasculitis and vasculopathy in the era of COVID-19 pandemic

“…In children, MIS-V had a frequency of 1.5 cases per million of injected doses, with patients aged 12–20 years, presenting with fever, coagulopathy, mucocutaneous, cardiac, gastrointestinal, and renal involvement. They were treated with systemic CS and/or IGIV and had a favorable outcome ( 111 , 114 ). Similarly, adult MIS-V forms are also reported, with comparable course, treatment, and outcome ( 112 , 115 – 118 ) ( Supplementary Table 6 ).…”