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

TY - JOUR

T1 - SARS-CoV-2, myocardial injury and inflammation

T2 - insights from a large clinical and autopsy study

AU - Dal Ferro, Matteo

AU - Bussani, Rossana

AU - Paldino, Alessia

AU - Nuzzi, Vincenzo

AU - Collesi, Chiara

AU - Zentilin, Lorena

AU - Schneider, Edoardo

AU - Correa, Ricardo

AU - Silvestri, Fulvio

AU - Zacchigna, Serena

AU - Giacca, Mauro

AU - Metra, Marco

AU - Merlo, Marco

AU - Sinagra, Gianfranco

N1 - Funding Information: We would like to thank Fondazione CRTrieste, Fondazione CariGO and Fincantieri for their support to our Research. MG is supported by the European Research Council (ERC) Advanced Grant 787971 “CuRE” and by Programme Grant RG/19/11/34633 from the British Heart Foundation. The authors wish to thank Giacomo Molinari, Katia Di Vito, Sonia De Luca, Marzia Pavlovich, Paola Suligoi, Ida Rosano, Gabriella Slatich and Lorena Ulcigrai for excellent technical support in autopsies, histology and immunohistochemistry. Finally, we want to thank all the healthcare professionals for the continuous support to the clinical management of patients affected by cardiomyopathies and followed in the Heart Failure Outpatient Clinic of Trieste. Publisher Copyright: © 2021, The Author(s).

PY - 2021/11

Y1 - 2021/11

N2 - 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. Graphic abstract: [Figure not available: see fulltext.]

AB - 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. Graphic abstract: [Figure not available: see fulltext.]

KW - Cardiac autopsy study

KW - COVID-19

KW - Myocardial injury

KW - Myocarditis

KW - Necrosis

UR - http://www.scopus.com/inward/record.url?scp=85110919383&partnerID=8YFLogxK

U2 - 10.1007/s00392-021-01910-2

DO - 10.1007/s00392-021-01910-2

M3 - Article

AN - SCOPUS:85110919383

SN - 1861-0684

VL - 110

SP - 1822

EP - 1831

JO - Clinical Research In Cardiology

JF - Clinical Research In Cardiology

IS - 11

ER -