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Background: Cardiac injury is common in hospitalized patients with COVID-19 and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with SARS-CoV-2 remain uncertain. Methods: We conducted a systematic pathologic analysis of 40 hearts from hospitalized patients dying of Coronavirus Disease 2019 (COVID-19) in Bergamo, Italy to determine the pathologic mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury. Results: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. As compared to subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and shorter symptom onset to admission. The incidence of severe coronary artery disease (i.e., >75% cross sectional narrowing) was not significantly different between those with and without necrosis. 3/14 (21 .4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction defined as ≥1 cm 2 area of necrosis while 11/14 (78.6%) showed evidence of focal (> 20 necrotic myocytes with an area of ≥ 0.05 mm 2 but <1 cm 2 ) myocyte necrosis. Cardiac thrombi were present in 11/14 (78.6%) cases with necrosis, with 2/14 (14.2%) having epicardial coronary artery thrombi while 9/14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19 positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19 infected patients presenting with ST-segment elevation myocardial infarction (STEMI). Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19 positive and negative STEMI patients. Conclusions: The most common pathologic cause of myocyte necrosis was microthrombi. Microthrombi were different in composition as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to coronary thrombi retrieved from COVID-19 positive and negative STEMI patients. Tailored anti-thrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.

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Iron is fundamental for life-essential processes. However, it can also cause oxidative damage, which is thought to trigger numerous pathologies, including cardiovascular diseases. The role of iron in the pathogenesis of atherosclerosis is still not completely understood. Macrophages are both key players in the handling of iron throughout the body and in the onset, progression and destabilization of atherosclerotic plaques. Iron itself might impact atherosclerosis through its effects on macrophages. However, while targeting iron metabolism within macrophages may have some beneficial effects on preventing atherosclerotic plaque progression there may also be negative consequences. Thus, the prevailing view of iron being capable of accelerating the progression of coronary disease through lipid peroxidation may not fully take into account the multi-faceted role of iron in pathogenesis of atherosclerosis. In this review, we will summarize the current understanding of iron metabolism in the context of the complex interplay between iron, inflammation, and atherosclerosis.