SARS-CoV-2, myocardial injury and inflammation: insights from a large clinical and autopsy study
Matteo Dal Ferro1,2, Rossana Bussani3, Alessia Paldino4,5
1Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Via Valdoni 7, 34123, Trieste, Italy. matteo.dalferro@asugi.sanita.fvg.it.
Insights
Myocardial injury is common in severe COVID-19, but overt myocarditis is rare and not linked to SARS-CoV-2 in heart cells. Chronic and acute damage often correlate with patient age, comorbidities, and disease severity.
Area of Science:
- Cardiology
- Virology
- Pathology
Background:
- Myocardial injury is frequently observed in hospitalized patients with COronaVIrus Disease 2019 (COVID-19).
- The precise mechanisms driving this cardiac damage and its association with SARS-CoV-2-mediated myocarditis remain poorly understood.
- Definitive evidence for SARS-CoV-2 presence and its role within cardiomyocytes in a clinical setting is lacking.
Purpose of the Study:
- To investigate the presence and role of SARS-CoV-2 in myocardial tissue of deceased COVID-19 patients.
- To determine the association between SARS-CoV-2 infection and myocarditis or myocardial damage.
- To characterize the histological findings in the myocardium of patients who died from severe SARS-CoV-2 infection.
Main Methods:
- Histological characterization of myocardial tissue from 40 deceased COVID-19 patients.
- Analysis of clinical data, including age and comorbidities.
- RT-PCR, immunohistochemistry for viral antigens, and in situ RNA hybridization to detect SARS-CoV-2 in myocardial tissue.
Main Results:
- Chronic and acute myocardial damage were consistently present, correlating with patient age and comorbidities.
- Overt myocarditis was found in only one case (2.5%).
- SARS-CoV-2 genome was not detected in the cardiomyocytes of the patient with myocarditis and was negligibly present in others without myocardial inflammation.
Conclusions:
- Myocarditis is infrequently diagnosed in this autopsy cohort of COVID-19 patients and is not associated with SARS-CoV-2 presence in cardiomyocytes.
- Chronic and acute myocardial damage are common findings in severe COVID-19.
- The extent of myocardial damage correlates with COVID-19 disease severity and pre-existing patient comorbidities.
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.
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