Enhanced platelet hyperreactivity is associated with COVID-19. Platelets were isolated from healthy donors (HDs), patients with ARDS unrelated to COVID-19, and patients with COVID-19 (with or without ARDS). (A) Quantification of platelet maximal aggregation for healthy donors (n = 10), for patients with ARDS unrelated to COVID-19 (n = 8), and for patients infected with SARS-CoV-2 (without ARDS [n = 5] and with ARDS [n = 5]) in response to α-thrombin activation. Statistical analysis was performed using ordinary one-way analysis of variance with Sidak’s multiple comparisons test. (B) Representative aggregation traces of washed platelets from healthy donors, patients with ARDS without COVID-19, and patients with ARDS and COVID-19 who were treated with α-thrombin (0.05 U/mL) under continuous stirring at 37°C. Times to reach 50% (T₅₀) aggregation are indicated below graph. Levels of (C) TBX₂, (D) PF4, (E) serotonin, and (F) sCD40L measured in plasma at time of platelet isolation were determined using commercial enzyme-linked immunosorbent assay kits. Statistical analysis was performed using paired Student t test. ns, not significant. *P < .05; **P < .01; ***P < .001; ****P < .0001.