Systemic inflammation in acute Sars-CoV-2 infection may lead to elevated cardiac cytokines and adverse remodeling

ABSTRACT

COVID-19, the clinical syndrome caused by severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection, has affected 15 million people globally as of August 2020. Myocardial injury, as evidenced by troponin elevation, is common during early SARS-CoV-2 infection and is predictive of poor outcomes. However, studying the effects of SARS-CoV-2 on the heart is difficult as tissue is generally only available from autopsy specimens late in the disease course. The non-human primate Rhesus macaque (RM) shares 91% homology of the ACE2 receptor to humans and has a similar susceptibility to infection and organ involvement as humans. Here, we sought to assess the acute effects of SARS-CoV-2 infection on the heart. Four (4) adult RM were infected with SARSCoV- 2 by intratracheal and intranasal inoculation and followed for 10 days. The virus was undetectable in cardiac tissue 10 days post inoculation (DPI), but we observed systemic inflammation at 4/5 DPI, with elevated CRP and ferritin levels. Immune cell infiltration was limited on flow cytometry of dissociated left ventricular tissue (n=1-2). Leukocyte numbers were about 32 CD45+ cells/mg, split evenly between macrophages and neutrophils. Half the macrophages were M2 (CD163+). About 71% of neutrophils were positive for the ACE2 receptor and CXCR2, and less than 10% had markers of NETosis. Surprisingly, we detected increased cardiac fibrosis assessed at necropsy (n=9), as well as elevated inflammatory cytokines IL-6 and TNF-alpha (n=5), compared to non-infected controls. In conclusion, while we saw no evidence of direct viral infection or significant immune response in the heart, the systemic inflammatory response to SARS-CoV-2 could be triggering adverse remodeling and fibrosis in the heart.