Pathological Evidence for SARS-CoV-2 as a Cause of Myocarditis

JACC Review Topic of the Week

Rika Kawakami, MD; Atsushi Sakamoto, MD; Kenji Kawai, MD; Andrea Gianatti, MD; Dario Pellegrini, MD; Ahmed Nasr, MD; Bob Kutys, PA; Liang Guo, PHD; Anne Cornelissen, MD; Masayuki Mori, MD; Yu Sato, MD; Irene Pescetelli, MD; Matteo Brivio, MD; Maria Romero, MD; Giulio Guagliumi, MD; Renu Virmani, MD; Aloke V. Finn, MD


J Am Coll Cardiol. 2021;77(3):314-325. 

In This Article

Abstract and Introduction


To investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)–induced myocarditis constitutes an important mechanism of cardiac injury, a review was conducted of the published data and the authors' experience was added from autopsy examination of 16 patients dying of SARS-CoV-2 infection. Myocarditis is an uncommon pathologic diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy. Although polymerase chain reaction–detectable virus could be found in the lungs of most coronavirus disease-2019 (COVID-19)–infected subjects in our own autopsy registry, in only 2 cases was the virus detected in the heart. It should be appreciated that myocardial inflammation alone by macrophages and T cells can be seen in noninfectious deaths and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis. Given its extremely low frequency and unclear therapeutic implications, the authors do not advocate use of endomyocardial biopsy to diagnose myocarditis in the setting of COVID-19.


Infection with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) confers significant risk of morbidity and mortality. Previous epidemiological data suggest that approximately 20% of hospitalized patients have evidence of cardiac injury as indicated by elevated levels of high-sensitivity troponins (hs-cTnI).[1] In 1 study in which troponin I was measured within 24 h of admission to assess cardiac damage, 36% of patients had elevated troponin I concentrations. After adjusting for disease severity and relevant risk factor differences, even small amounts of myocardial injury were associated with increased mortality.[2] However, much remains unknown about the nature of myocardial injury in patients with coronavirus disease-2019 (COVID-19). In the absence of obstructive epicardial coronary disease but evidence of myocardial injury (defined as positive troponin with or without wall motion abnormalities), physicians often default to the diagnosis of myocarditis as the underlying cause using data such as clinical and imaging markers of myocyte injury. Indeed, most published cases of presumed myocarditis induced by COVID-19 infection were based on blood troponin levels or cardiac magnetic resonance imaging (CMR) without tissue diagnosis.[3–5] However, direct evidence for myocarditis in the setting of SARS-CoV-2 remains very limited.[6,7] A complete understanding of the pathogenesis of cardiac injury in the setting of COVID-19 infection is critical for the development of appropriate treatments.