Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults

BACKGROUND: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19–related myocarditis. OBJECTIVES: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling MIS-A criteria (MIS-A(+)) or not (MIS-A(−)). METHODS: A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU). RESULTS: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A(−) patients compared with MIS-A(+) patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A(−) patients (31% vs 4%). MIS-A(+) had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A(−) had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A(−) patients (54%) but in none of the MIS-A(+) patients. CONCLUSION: MIS-A(+) and MIS-A(−) fulminant COVID-19–related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients’ management and further understanding of their pathophysiology.