Publications & Posters

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

Journal of the American College of Cardiology | July 26, 2022

Barhoum P, Pineton de Chambrun M, Dorgham K, Kerneis M, Burrel S, Quentric P, Parizot C, Chommeloux J, Bréchot N, Moyon Q, Lebreton G, Boussouar S, Schmidt M, Yssel H, Lefevre L, Miyara M, Charuel JL, Marot S, Marcelin AG, Luyt CE, Leprince P, Amoura Z, Montalescot G, Redheuil A, Combes A, Gorochov G and Hékimian G

J Am Coll Cardiol. 2022;80:299-312

This study was performed using the Quanterix HD-1 Analyzer.



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.


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−).


A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU).


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.


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.