Microthrombi are the most common cause of cardiac injury in patients with COVID-19, according to a systematic pathology analysis of 40 hearts from patients who died from COVID-19 in Bergamo, Italy. Pellegrini and colleagues found that 35% of the patients had evidence of cardiomyocyte necrosis, mainly of the left ventricle. The most common cause of the cardiomyocyte necrosis was microthrombi, found in 64% of hearts with necrosis. The microthrombi were different in composition (richer in fibrin and terminal complement) from intramyocardial thrombi from patients without COVID-19 and from coronary thrombus aspirates from patients with STEMI with or without COVID-19. Of note, the frequency with which viral RNA was detected in the heart was not significantly different in those with or without myocardial necrosis (14.3% versus 23.1%), suggesting that direct viral infection of the myocardium does not have a major role in the necrosis. The investigators suggest that tailored antithrombotic strategies might be useful to counteract the cardiac effects of microthrombi (which would not be detectable clinically owing to the lack of laboratory tests) and should be examined in future studies.