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


SARS-CoV-2 infection carries significant morbidity and mortality, especially in the setting of concomitant cardiac injury. However, the mechanism by which the virus causes cardiac damage remains uncertain. Because of the known relationship between viral infection and myocarditis, COVID-19–induced myocarditis has been suggested to be a major mechanism. A thorough review of the literature describing both EMB and autopsy sample analysis suggests that myocarditis is an uncommon diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or EMB (Central Illustration). Given the referral bias of autopsy studies, it is likely the number of COVID-19 cases complicated by myocarditis is even lower, because the majority of cases do not have evidence of myocardial injury and do not result in death. However, it should also be appreciated that myocardial inflammation involving infiltration by macrophages and T cells can also be seen in noninfectious deaths (control) and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis. Indeed, in the hearts of SARS-CoV-2 infected subjects, nonspecific inflammatory infiltrate characterized by macrophages was more abundant whereas T cells were lower compared with hearts from cases of control deaths (Central Illustration). This finding may be consistent with the known lymphope5nic effects of the virus, but deserves further investigation. Nonetheless, our data suggest evidence that COVID-19–induced myocarditis is an uncommon phenomenon. Given this fact and the unclear therapeutic implications of identifying viral myocarditis in subjects with COVID-19, the authors believe EMB should not be routinely used and perhaps should be reserved for worst case scenarios such as patients with new-onset fulminant heart failure with hemodynamic compromise in the setting of documented COVID-19 infection.

Central Illustration.

Histological Evidence of Myocarditis in COVID-19 Infection and Numbers of Infiltrated Inflammatory Cells in Myocardium in COVID-19 Autopsy Hearts Without Myocarditis and in Non–COVID-19 Myocarditis
According to published data on pathological evidence for myocarditis in subjects with coronavirus disease-2019 (COVID-19), the rate of myocarditis is 4.5%. In our experience with 16 COVID-19 autopsy cases, no case met diagnostic criteria for myocarditis. In a comparison of inflammatory cells in the myocardium of subjects dying from traumatic versus COVID-19 deaths (but without a diagnosis of myocarditis), there were less cluster of differentiation (CD) 3–positive cells in COVID-19 cases and more CD68-positive cells.