Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases

Abstract

n patients with coronavirus disease 2019 (COVID-19), cardiovascular involvement occurs frequently. Myocardial injury with elevated troponin levels is described in patients hospitalized with COVID-19 1 and seems to be associated with outcome. 2 The origin of myocardial injury can result from ischemia due to thrombotic coronary obstruction but can also include other causes such as heart failure, pulmonary embolism, tachycardia, and sepsis. 3 Obviously, an infection of the myocardium with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is another alternative for elevated troponin. Next to elevated biomarkers for cardiac injury, myocardial dysfunction determined by echocardiography is also reported in up to 70% of hospitalized patients. 4 This makes cardiac involvement during COVID-19, which manifests primarily as a pulmonary disease, likely.Myocarditislike clinical presentations have been described in only a few patients with COVID-19 to date, 5 suggesting that fulminant myocarditis is rare. 6 In the very few cases with clinically suspected myocarditis, SARS-CoV-2 infection was associated with cardiac inflammation. 7 Whether SARS-CoV-2 can be documented and replicates within the heart and whether this is associated with mononuclear cell infiltration or induces cytokine expression remains elusive in deceased patients without clinically overt myocarditis. Therefore, we investigated whether myocardial infection occurred in autopsy cases of patients with COVID-19. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown.OBJECTIVE To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests.EXPOSURES Patients who died of coronavirus disease 2019. MAIN OUTCOMES AND MEASURESIncidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3 + , CD45 + , and CD68 + cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18.RESULTS Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field. CO...

SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients

“…To date, most myocardial histology from autopsy specimens of COVID-19 patients have revealed only general signs of myopathy, such as edema, occasional mononuclear infiltrate, and mild hypertrophy 18 . Although 30-50% of COVID-19 patients manifest clinical signs of cardiac dysfunction 13,38 , histological hallmarks of COVID-19 in the heart have remained elusive.…”

“…Although our results show that direct infection of CMs may not be required to elicit cytotoxic effects in cardiac tissue, evidence of cardiomyocytes directly infected by SARS-CoV-2 in COVID-19 patients remains scant. Analyses of the myocardium of post-mortem COVID-19 patients have detected viral dsRNA, 18 but failed to detect staining of viral particles in cardiomyocytes at the time of death. More recent reports describe detection of SARS-CoV-2 particles for the first time inside the cardiomyocytes of COVID-19 patients 19,20 , while many autopsy specimens have undetectable virus in the heart 18,21 .…”

“…Analyses of the myocardium of post-mortem COVID-19 patients have detected viral dsRNA, 18 but failed to detect staining of viral particles in cardiomyocytes at the time of death. More recent reports describe detection of SARS-CoV-2 particles for the first time inside the cardiomyocytes of COVID-19 patients 19,20 , while many autopsy specimens have undetectable virus in the heart 18,21 . We hypothesize that if virus is present in myocytes during an early to progressive stage of the disease, assays on deceased patient tissue may be limited the window of opportunity to detect transient viral presence in cardiomyocytes.…”

“…Reports of cardiac dysfunction incidence in COVID-19 patients range from 20% to 50%, independent of disease severity 8,13,38 . Cardiac damage is strongly associated with disease mortality 3,8,18,20,46 . In addition, due to the heart's innate lack of regenerative capacity 47,48 , a majority of these patients could suffer long-term cardiac sequelae from COVID-19.…”

Gamut of Cardiac Manifestations and Complications of COVID-19: A Contemporary Review

“…7 11 Pathologic specimens show a spectrum of myocardial involvement, ranging from few interstitial mononuclear inflammatory infiltrates without substantial myonecrosis 26 to viral presence within the myocytes. 27 A postmortem study of patients who died from COVID-19 documented SARS-CoV-2 in 61.5% of the hearts, with a high viral load (>1000 copies/μg RNA) in 41% of patients. Interestingly, viral presence in the myocardium was not associated with influx of inflammatory cells in the interstitium.…”