COVID-19 and myocarditis: a systematic review and overview of current challenges

Abstract

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19-30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.

Keywords: 2019nCoV; COVID-19; Cardiac damage; Cardiac injury; Coronavirus; Myocardial damage; Myocarditis; SARS-CoV-2.

Fig. 1

Harvest plot summarizing demographic characteristics, imaging findings and treatment in patients with COVID-19 and myocarditis to the outcome

Fig. 2

Central illustration. Current evidence on acute myocarditis in patients with COVID-19

Fig. 3

Microscopic study of the heart from a deceased patient with COVID-19 and cardiogenic shock in Bergamo, Italy. Numerous microthrombi of the left ventricle are shown without evidence of an inflammatory infiltrate; the detection on tissue by molecular technique for SARS-CoV-2 was negative. Collectively, the diagnosis of COVID-19 related myocarditis was excluded in view of the thorough histological evaluation that proved absence of myocyte necrosis and inflammatory infiltrate