Multisystem Inflammatory Syndrome in Children After SARS-CoV-2 Vaccination

Eisha Jain; Jeffrey R. Donowitz; Elizabeth Aarons; Beth C. Marshall; Michael P. Miller


Emerging Infectious Diseases. 2022;28(5):990-993. 

In This Article


This report describes 2 cases of MIS-C within 1 week of receiving the first dose of BNT162b2. There is no specific test for MIS-C; although both patients met diagnostic criteria, alternative diagnoses were possible. Patient 2 had costovertebral angle tenderness, unilateral renal enlargement, and 10,000 CFU/mL growth of a uropathogen on culture. Given the low level of bacterial growth, lack of enhancement on her CT, and constellation of lab and imaging abnormalities not commonly seen with urinary tract infections, MIS-C remains her most likely diagnosis.

Patient 1 had a positive antinucleocapsid antibody suggesting community-acquired COVID-19 infection before MIS-C developed (P.D. Burbelo et al., unpub. data, Salzman et al. describe 3 similar cases in which MIS or an MIS-like illness developed after COVID-19 vaccination, particularly in the setting of community-acquired COVID-19.[3] The chronology of events in these cases raises the possibility that vaccination may be involved in the pathogenesis of MIS-C when preceded by community-acquired SARS-CoV-2.

The pathogenesis of MIS-C is thought to involve immune dysregulation and hyperinflammation.[4] Studies have identified high levels of receptor-binding protein (RBD) antibodies in children with severe MIS-C.[5,6] Both natural SARS-CoV-2 infection and BNT162b2 vaccination have been shown to elicit RBD antibodies.[7] It may be possible that the immune responses to these 2 forms of exposure to SARS-CoV-2 interact to shape the manifestations of mild MIS-C in the postinfectious period of COVID-19. Although both of these cases were mild, we have insufficient data on the pathogenesis of MIS-C to understand how vaccination may shape symptomatology.

A recent report by Zambrano et al. documented that 61/97 (62.9%) MIS-C cases in unvaccinated patients required ICU admission.[8] That report had a small number of vaccinated cases; 1 in 5 of those vaccinated needed ICU care.[8] An analysis of postvaccination MIS-C in 21 patients showed that 3 (14%) required invasive mechanical ventilation, 8 (38%) required vasopressors, and 12 (57%) required ICU care (A.R. Yousaf et al., unpub. data, In contrast to Zambrano et al.'s vaccinated cases and our reported cases, the Yousaf et al. report suggests a similar number of ICU admissions in vaccinated and unvaccinated persons.

Studies have shown that COVID-19 vaccination is associated with reduced incidence of MIS-C, especially if 2 doses are given. A study of MIS-C cases in France during September–October 2021 found a significantly lower risk of MIS-C among vaccinated adolescents than those who were unvaccinated.[9] Zambrano et al. found a 91% protective effect of complete (2 doses) BNT162b2 vaccination against MIS-C.[8] Phase 2 and phase 3 clinical trials of BNT162b2 revealed 0 cases of MIS-C after vaccination.[10] Despite the reports of postvaccination MIS-C, vaccination clearly lowers the overall MIS-C burden, probably by preventing infection. These studies also suggest low likelihood of vaccination triggering development of MIS-C.

If vaccination can play a role in MIS-C pathogenesis, it is likely an extremely rare event and may involve an underlying genetic predisposition or be contingent on extraneous factors like recent SARS-CoV-2 community exposure. Our findings in 2 cases of MIS-C within 1 week of a dose of BNT162b2 raise the possibility that vaccination may alter the symptom profile of MIS-C.