ABSTRACT
Background: Angiotensin-converting enzyme 2, the target cellular receptor of SARS-CoV-2, is known to be present in adipose tissue. SARS-CoV-2 could enter the heart via the epicardium because the myocardium and the epicardium share the same microcirculation and are not separated from one another by a fascial layer. Previous studies demonstrated that macrophages play an important role in inflammation in adipose, including epicardial, tissue. In this study, we explore two hypotheses: a) there is no significant difference between the density of macrophages in the epicardium of patients who died with Covid-19 infection and those who died with non-Covid-19 acute lung injury, and b) the density of macrophages in the epicardium does not correlate with histological evidence of focal myocyte necrosis in patients who die of Covid-19 infection. Design: We compared the density of macrophages in the epicardium of 10 patients who died of complications of Covid-19 infection to that in a control group of 10 decedents with non-Covid related acute lung injury. Further, macrophage densities of those with and without histological evidence of focal myocardial damage were compared within the Covid-19 group. Three blocks were routinely sampled from each case (right ventricle, left ventricle and septum). All the sections were stained with CD68 as a macrophage marker. The density of CD68-positive cells in the epicardium was determined by counting the number of cells in five hot spot regions (each 3 mm2) at 100x. Quantification was performed using imageJ and is expressed as cells/mm2. The densities of CD68- positive macrophage were compared using T-test. The clinical characteristics between the groups were compared using Fischer exact test. P-value < 0.05 is significant. Results: The density of CD68-positive macrophages in the epicardium is significantly higher in Covid-19 patients compared to the control group. The CD68-macrophage count is also significantly higher in hearts of Covid-19 decedents with histological evidence of focal myocyte necrosis than those with no evidence of myocyte necrosis. There are no significant differences in other characteristics between the groups (Table, Figure). Conclusions: Contrary to our hypotheses, the density of CD68-positive macrophages is strongly correlated with Covid-19 infection and Covid-19 related myocyte necrosis. Further studies are needed to understand the pathophysiologic relationship between epicardial inflammation and myocyte necrosis.