The mechanisms underlining thrombosis in COVID-19 patients are not known and likely due to multiple processes including inflammation, oxygen demand injury, and plaque rupture triggered by the infection. Platelets mediate thrombotic vascular occlusion but are also increasingly recognized to have immunomodulatory activity. Several of our recent studies have characterized the role of viral infections in cardiac disease. Although robust data on the scope of acute myocardial infarction in COVID-19 are not yet available, myocardial infarction contributed to in-hospital mortality during previous severe acute respiratory syndrome/coronavirus epidemics. A recent study has also demonstrated that influenza and other respiratory viruses increase the incidence of acute myocardial infarction particularly in the first 7 days post-infection, suggesting that platelets may be directly involved in mediating an immune response but, when dysregulated, can also lead to thrombotic vascular occlusion.