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
medRxiv(2022)
Abstract
Background Multisystem 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.
Methods We 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.
Findings We 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.
Interpretation In 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.
Funding This 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.
Evidence before this study Multisystem 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 study We 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 evidence During 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.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
This work was supported by Centers for Disease Control and Prevention Clinical Immunization Safety Assessment (CISA] Project contracts to Vanderbilt University Medical Center and to Cincinnati Childrens Hospital Medical Center.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
This activity reviewed by CDC IRB and determined to be a non-research public health surveillance activity.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
All data produced in the present study are available upon reasonable request to the authors
MoreTranslated text
Key words
multisystem inflammatory syndrome,vaccine
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined