SARS-CoV-2, myocardial injury and inflammation: insights from a large clinical and autopsy study

Abstract

Objective: Despite growing evidence about myocardial injury in hospitalized COronaVIrus Disease 2019 (COVID-19) patients, the mechanism behind this injury is only poorly understood and little is known about its association with SARS-CoV-2-mediated myocarditis. Furthermore, definite evidence of the presence and role of SARS-CoV-2 in cardiomyocytes in the clinical scenario is still lacking.

Methods: We histologically characterized myocardial tissue of 40 patients deceased with severe SARS-CoV-2 infection during the first wave of the pandemic. Clinical data were also recorded and analyzed. In case of findings supportive of myocardial inflammation, histological analysis was complemented by RT-PCR and immunohistochemistry for SARS-CoV-2 viral antigens and in situ RNA hybridization for the detection of viral genomes.

Results: Both chronic and acute myocardial damage was invariably present, correlating with the age and comorbidities of our population. Myocarditis of overt entity was found in one case (2.5%). SARS-CoV-2 genome was not found in the cardiomyocytes of the patient with myocarditis, while it was focally and negligibly present in cardiomyocytes of patients with known viral persistence in the lungs and no signs of myocardial inflammation. The presence of myocardial injury was not associated with myocardial inflammatory infiltrates.

Conclusions: In this autopsy cohort of COVID-19 patients, myocarditis is rarely found and not associated with SARS-CoV-2 presence in cardiomyocytes. Chronic and acute forms of myocardial damage are constantly found and correlate with the severity of COVID-19 disease and pre-existing comorbidities.

Keywords: COVID-19; Cardiac autopsy study; Myocardial injury; Myocarditis; Necrosis.

Fig. 1

Hematoxylin–Eosin staining of cardiac tissue showing different forms of damage. a Sample 210, wavy myocells (× 10), b Sample 272, CM hypertrophy (× 10), c Sample 272, CM hypertrophy (× 40), d Sample 197, Interstitial fibrosis (× 20), e Sample 165, CM apoptosis (× 20), f Sample 241, CM apoptosis e necrobiosis (× 40), g Sample 300, CM necrosis, apoptosis and hypertrophy (× 40), h Sample 207, CM necrosis, apoptosis (× 20), I Sample 197, IHC for Annexin V (× 40), l Sample 285, Substitutive fibrosis (× 10), m Sample 235, severe substitutive fibrosis (× 10), n Sample 288, amyloidosis (× 10), o Sample 314, overt lymphocytic myocarditis (× 20), p Sample 354, lymphocytic epicarditis (× 10), q Sample 262, spotty lymphocytic myocarditis (× 20), r Sample 285, lymphocytic epicarditis (× 10)

Fig. 2

Cardiac ISH of SARS-CoV-2 RNA and IHC against SARS-CoV-2 Spike protein on patients with no myocarditis and known viral persistence in the lungs (n°207 and 210) and in a representative patient with myocarditis (n°262). a Sample 207, Probe SARS-CoV-2 Rna; b Sample 207, Probe SARS-CoV-2 Rna; c Sample 207, Antibody SARS-CoV-2 Spike; d Sample 207, hematoxylin–eosin. e Sample 210, Probe SARS-CoV-2 Rna; f Sample 210, Probe SARS-CoV-2 Rna; g Sample 210, Antibody: SARS-CoV-2 Spike; h Sample 210, hematoxylin–eosin. i Sample 262, Probe control U6; l Sample 262, Probe SARS-CoV-2 Rna; m Sample 262, hematoxylin–eosin

Fig. 3

Correlation between Pneumonia severity (Grade 1–5) and Myocardial necrosis (Grade 1-focal- to 4 -diffuse, severe-): R² = 0.37; p < 0.0001