Fatal Multisystem Inflamatory Syndrome in Adult After SARS-CoV-2 Natural Infection and COVID-19 Vaccination

Heather N. Grome; Michael Threlkeld; Steve Threlkeld; Charles Newman; Roosecelis Brasil Martines; Sarah Reagan-Steiner; Michael A. Whitt; Maria Gomes-Solecki; Nisha Nair; Mary-Margaret Fill; Timothy F. Jones; William Schaffner; John Dunn


Emerging Infectious Diseases. 2021;27(11):2914-2918. 

In This Article


This fatal case of MIS-A occurred after full COVID-19 vaccination in a patient with prior natural SARS-CoV-2 infection suspected 6 weeks before MIS-A symptom onset. Serum antibody results before IVIg infusion indicated the patient was previously infected with SARS-CoV-2 and was vaccinated with a COVID-19 vaccine. Antibodies to the nucleocapsid protein are the most sensitive target for serologic diagnosis for natural infection (P.D. Burbelo et al., unpub. data, https://doi.org/10.1101/2020.04.20.20071423), and these antibodies are not present following COVID-19 vaccination alone. In addition, clinical history was compatible with natural infection beginning 6 days before the first mRNA vaccine dose and consistent with negative SARS-CoV-2 nucleocapsid IgM on testing during hospitalization.

The patient demonstrated similar clinical findings to previously reported MIS-A cases, including fever for 3 consecutive days, laboratory evidence of inflammation, neurologic and mucocutaneous clinical findings, and severe cardiac illness that included systemic hypotension progressing to cardiogenic shock.[1,5] These criteria meet the CDC case definition for MIS-A, as well as a definitive case at level 1 of diagnostic certainty by the Brighton collaboration case definition for MIS-A and MIS-C.[10] In addition, the histopathologic findings of capillaritis and multiorgan microvascular thrombosis in association with clinical symptoms and laboratory findings are compatible with MIS-A.[1,11] Substantial blood loss on gross examination may represent a diffuse intravascular coagulation–type picture in which diffuse microthrombosis depleted platelets and clotting factors. The etiology for clinical deterioration was likely multifactorial, although considerable cardiac compromise in the setting of high fluid volumes and intraperitoneal hemorrhage may have contributed to multiorgan failure

Whether mRNA COVID-19 vaccination contributed to MIS-A onset in this case is unclear, and future epidemiologic studies are needed to understand whether an association exists. The immunopathology leading to hyperinflammation causing MIS-A after SARS-CoV-2 infection remains unknown, although postinfection immune dysregulation is consistent among reported cases. Notably, MIS-A has not been reported among adult participants of COVID-19 vaccine trials,[10] and no direct evidence exists to support vaccine alone as the primary etiology in this case. This article further emphasizes the importance of COVID-19 prevention, for which infection prevention strategies and vaccination remain our greatest defense.