The Pathogenisis of COVID-19 Myocardial Injury: an Immunohistochemical Study of Postmortem Biopsies
Abstract Rationale: Myocardial injury is significantly and independently associated with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 is still not clear, and cardiac involvement by SARS-CoV-2 remains a major challenge worldwide. Objective: This histopathological and immunohistochemical study seeks to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury. Methods and Results: Postmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control patient. Histopathological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against the following targets: caspase-1, ICAM-1, TNF-α, IL-4, IL-6, CD163, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also subjected to a TUNEL assay to detect potential apoptosis. The histopathological analysis showed severe pericellular interstitial edema surrounding each of the cardiomyocytes and higher mast cells count by high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-4, IL-6, CD163, MMP-9 and type 3 collagen in the COVID-19 patients compared to the control. No difference from the control was observed in expression of TNF-α, TGF-β and type 1 collagen. The TUNEL assay was positive in all the COVID-19 samples confirming the presence of endothelial apoptosis. Conclusions: The pathogenesis of COVID-19 myocardial injury seems to be related with pyroptosis leading to endothelial cell injury and disfunction. The subsequent inflammation with associated interstitial edema could explain the myocardial disfunction and arrythmias in these patients. Our findings also show that COVID-19 myocardial injury may cause myocardial fibrosis in the long term. These patients should be monitored for myocardial dysfunction and arrythmias after the acute phase of COVID-19.