Characterization of COVID-19-associated cardiac injury: evidence for a multifactorial disease in an autopsy cohort

As the coronavirus disease 2019 (COVID-19) pandemic evolves, evidence has implicated the heart as a critical target of injury. We examined purported mechanisms of COVID-19-associated heart damage in 21 COVID-19-positive decedents, compared to clinically matched controls and other etiologies of viral myocarditis in a custom tissue microarray, via immunohistochemistry and in situ hybridization. Collectively, COVID-19-associated cardiac injury was multifactorial, with elevated levels of neutrophil extracellular traps and von Willebrand factor as defining features of direct and indirect viral-associated injury. As the coronavirus disease 2019 (COVID-19) pandemic evolves, much evidence implicates the heart as a critical target of injury in patients. The mechanism(s) of cardiac involvement has not been fully elucidated, although evidence of direct virus-mediated injury, thromboembolism with ischemic complications, and cytokine storm has been reported. We examined suggested mechanisms of COVID-19-associated heart failure in 21 COVID-19-positive decedents, obtained through standard autopsy procedure, compared to clinically matched controls and patients with various etiologies of viral myocarditis. We developed a custom tissue microarray using regions of pathological interest and interrogated tissues via immunohistochemistry and in situ hybridization. Severe acute respiratory syndrome coronavirus 2 was detected in 16/21 patients, in cardiomyocytes, the endothelium, interstitial spaces, and percolating adipocytes within the myocardium. Virus detection typically corresponded with troponin depletion and increased cleaved caspase-3. Indirect mechanisms of injury-venous and arterial thromboses with associated vasculitis including a mixed inflammatory infiltrate-were also observed. Neutrophil extracellular traps (NETs) were present in the myocardium of all COVID-19 patients, regardless of injury degree. Borderline myocarditis (inflammation without associated myocyte injury) was observed in 19/21 patients, characterized by a predominantly mononuclear inflammatory infiltrate. Edema, inflammation of percolating adipocytes, lymphocytic aggregates, and large septal masses of inflammatory cells and platelets were observed as defining features, and myofibrillar damage was evident in all patients. Collectively, COVID-19-associated cardiac injury was multifactorial, with elevated levels of NETs and von Willebrand factor as defining features of direct and indirect viral injury.

Automated summary

As the COVID-19 pandemic continues, it becomes evident that the heart is a critical target of injury. This study explored the mechanisms of COVID-19-associated heart damage using tissue samples from 21 COVID-19-positive deceased individuals. The findings suggest that elevated levels of neutrophil extracellular traps (NETs) and von Willebrand factor are defining features of direct and indirect viral-related heart injury.