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% vs4%). MIS-A(+) had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-alpha (TNF-alpha), whereas MIS-A(-) had higher interferon-alpha 2 (IFN-alpha 2) 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. (C) 2022 by the American College of Cardiology Foundation.