The Density of CD-68 Positive Macrophages in the Epicardium Correlates with Covid-19 Infection in Deceased Patients

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.