Abstract
COVID-19 has been associated with cardiac injury and dysfunction. While both myocardial inflammatory cell infiltration and myocarditis with myocyte injury have been reported in patients with fatal COVID-19, clinical–pathologic correlations remain limited. The objective was to determine the relationships between cardiac pathological changes in patients dying from COVID-19 and cardiac infection by SARS-CoV-2, laboratory measurements, clinical features, and treatments. In a retrospective study, 41 consecutive autopsies of patients with fatal COVID-19 were analyzed for the associations between cardiac inflammation, myocarditis, cardiac infection by SARS-CoV-2, clinical features, laboratory measurements, and treatments. Cardiac infection was assessed by in situ hybridization and NanoString transcriptomic profiling. Cardiac infection by SARS-CoV-2 was present in 30/41 cases: virus+ with myocarditis (n = 4), virus+ without myocarditis (n = 26), and virus– without myocarditis (n = 11). In the cases with cardiac infection, SARS-CoV-2+ cells in the myocardium were rare, with a median density of 1 cell/cm2. Virus+ cases showed higher densities of myocardial CD68+ macrophages and CD3+ lymphocytes, as well as more electrocardiographic changes (23/27 vs 4/10; P = 0.01). Myocarditis was more prevalent with IL-6 blockade than with nonbiologic immunosuppression, primarily glucocorticoids (2/3 vs 0/14; P = 0.02). Overall, SARS-CoV-2 cardiac infection was less prevalent in patients treated with nonbiologic immunosuppression (7/14 vs 21/24; P = 0.02). Myocardial macrophage and lymphocyte densities overall were positively correlated with the duration of symptoms but not with underlying comorbidities. In summary, cardiac infection with SARS-CoV-2 is common among patients dying from COVID-19 but often with only rare infected cells. Cardiac infection by SARS-CoV-2 is associated with more cardiac inflammation and electrocardiographic changes. Nonbiologic immunosuppression is associated with lower incidences of myocarditis and cardiac infection by SARS-CoV-2.
【초록키워드】 COVID-19, SARS-CoV-2, Inflammation, Macrophage, Lymphocytes, Infection, Comorbidities, Immunosuppression, Autopsy, glucocorticoid, Clinical features, Retrospective study, lymphocyte, myocarditis, Patient, incidence, correlation, change, association, cardiac, Injury, IL-6 blockade, changes, dysfunction, Myocardium, infected cells, fatal COVID-19, laboratory measurements, while, CD3+, inflammatory cell infiltration, transcriptomic, Myocardial, Cell, prevalent, analyzed, reported, median, less, determine, pathological change, CD68+ macrophage, duration of symptom, electrocardiographic, infection with SARS-CoV-2, patients treated, positively correlated, 【제목키워드】 Inflammation, SARS-COV-2 infection, myocarditis, Factor, Myocardial, patients with COVID-19,