Activation of immune system may cause pathophysiological changes in the myocardium of sarscov-2 infected macaque model

ABSTRACT

Background: Recent reports suggest the presence of the SARS-CoV-2 virus in the myocardium of patients who died from the COVID-19 disease. Cardiovascular injury in COVID-19 patients is an established extra-pulmonary manifestation of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection which may lead to induction of arrhythmia, acute heartfailure, thickening of ventricular wall, reduced ejection fraction and thromboembolism. Non-human primates (NHP) provide a useful model to study cardiovascular changes due to their homology to the ACE2 receptor in humans. Aim: The aim of this study is to characterize the pathological changes in the heart of SARS-CoV-2 infected NHPs. Methods: In the present study, SARS-CoV-2 infected primates via aerosol route (n=4), multi-routes (i.e., oral, nasal, intratracheal and conjunctival) (n=4), and a control group (n=5) were included. Heart tissue samples were collected and the left ventricular tissue was analyzed by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to CD3, CD68 andSARS-CoV-2 nucleocapsid protein.Results: Several pathological findings were observed in the heart, including cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells as well as hypertrophy. Collagen specific staining showed development of cardiac fibrosis in the interstitial as well as in the perivascularregion in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. Additionally, SARS-CoV-2 nucleocapsid protein staining detected the presence of virus particles in the myocardium. Conclusion: COVID19 infection is characterized by exaggerated inflammatory immune response in the heart which possibly contributes to myocardial remodeling and subsequent fibrosis. These findings suggest progression of disease which could lead to development of severe complications including heart failure.