Detection of viral SARS‐CoV‐2 genomes and histopathological changes in endomyocardial biopsies

Abstract

Aims Since December 2019, the novel coronavirus SARS-CoV-2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID-19 have been reported. SARS-CoV-2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. Methods and results Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS-CoV-2 genomes by real-time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS-CoV-2 infected by reverse real-time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. Conclusions This is the first report that established the evidence of SARS-CoV-2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB-based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS-CoV-2infection and to design future specific and personalized treatment strategies.

Myocardial Injury in Post Mortem Biopsies of Patients with COVID-19

“…The rst two biomarkers, ICAM-1 and IL-6, were present in large quantities in the endothelial cells and indicate endothelial activation as well as immune cell recruitment and response. These ndings are in line with the observations on caspase-1, and with previous biopsies studies which had already shown that the in ammatory process in cardiac tissue permeates the vascular wall 6,10 . SARS-CoV-2 potentially causing endotheliitis 9 , which is determinant of microvascular dysfunction by shifting the vascular equilibrium towards more vasoconstriction with subsequent organ ischemia, in ammation with associated tissue edema, and a procoagulant state 18 .…”

“…The high levels of MMP-9, CD163, IL-4 and IL-6 demonstrate myocardial in ammatory stress in the COVID-19 tissue. SARS-CoV-2 particles have been already observed in a cytopathic interstitial in ammatory cell in myocardial tissue 8 and other autopsies of patients with COVID-19 also revealed in ltration of the myocardium by interstitial mononuclear in ammatory cells 6,8 . MMP-9 is a endopeptidase which cleaves structural elements of the extracellular matrix and also plays important roles in immune cell function 20 .…”

“…Recently, the evidence of SARS-CoV-2 genome detection in endomyocardial biopsies proved that SARS-CoV-2 infection directly impair the heart 6 . However, the mechanism of cardiac damage by SARS-CoV-2 is not clear and remains a major challenge worldwide.…”

“…Interstitial myocardial has been described as a possible mechanism for myocardial injury 6,12 in a process initiated by intercellular edema, which is accompanied by endothelial stress and consequent innate immune system recruitment through endothelial ICAM-1 expression 13 . Once the immune cells, notably Th2 type cells, have migrated to the site of the injury or aggression, they start secreting interleukins and pro-brotic chemokines as well as inducing matrix metalloproteinases and subsequent type 1 and type 3 collagen secretion by surrounding tissue broblasts 14 .…”

COVID-19 und das Herz

“…Grundsätzlich können systemische Viruserkrankungen eine Myokarditis auslösen. Dieses scheint aber bei COVID-19 eher selten zu sein, da es bisher nur wenige Fallberichte dazu gibt [6]. In diesen Fallberichten zeigt sich eine Myokarditis vor allem auch durch eine erhöhte Einwanderung von Entzündungszellen in das Myokard.…”