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. Graphic abstract

Prevalence of Acute Pulmonary Embolism at Autopsy in Patients With COVID-19

“…After excluding duplicates and preliminary screening, 155 full-text articles were assessed for eligibility, and 141 studies were excluded for not meeting the inclusion criteria, leaving 13 studies fulfilling the inclusion criteria ( Figure 1 , Supplementary File 2 ). 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19

Figure 1 Flow diagram of selected studies for the meta-analysis according to the PRISMA. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

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“… 9 Zambia 21 40 (12.3) 14 (66.2 %) 3 (14.3 %) 3 (14.3 %) 1 (4.8 %) NR NR 3 (14.2 %) Dal Ferro et al. 10 Italy 40 79 (11) 22 (55 %) NR 15 (37 %) 10 (24 %) NR NR NR Romanova et al. 11 Russia 42 69 (15) † 72 (15) ‡ 22 (52.3 %) 17 (40.4 %) 38 (90.4 %) 11 (26.1 %) NR NR NR Bryce et al.…”

“…The cumulative autopsy prevalence of acute PE in patients with COVID-19 ranged between 3.8% and 50.0% in 10 studies, enrolling 526 subjects (mean age 63.8 years). 6,7,9,10,[12][13][14][15]17,18 A random-effect model revealed a pooled prevalence of autoptic acute PE findings in 27.5% of cases (95% CI 15.0 to 45.0%, I 2 89.9%) (Figure 3). Both the Egger's test (t 0.522, p = 0.61) and visual inspection of the relative funnel plot (Supplementary File 3) did not reveal significant evidence of publication bias.…”

Cardiovascular Damage in COVID-19: What We Know Two Years Later

“…In this scenario, acute myocarditis may be responsible for the myocardial damage. This issue has been reported in several case reports, some of them also testing myocardial tissue by endomyocardial biopsy or post-mortem autopsy [ 7 •, 19 ]. However, in none of these cases a direct cause–effect relation between COVID-19 and acute cardiac inflammatory disease has been reported.…”

“…Interestingly, viral genome and Spike protein were not found in heart samples of patients with myocarditis. Authors suggested, supported by histopathological findings, that acute hypoxic cardiomyopathy, or the combination of acute hypoxia and pre-existing cardiac disease, along with a cytokine storm, is the main culprits of COVID-19-related cardiac injury [ 19 ].…”