Abstract 11039: Platelets Contribute to Disease Severity in Covid-19

Objective: Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Platelets are key regulators of thrombosis, inflammation, immunity and are prime candidates for a role in the pathogenesis of COVID-19. The objective of this study was to analyze the platelet phenotype in COVID-19. Approach and Results: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is detected in human megakaryocytes and platelets in COVID-19 patients and following incubation with the virus in vitro . We show a direct interaction between SARS-CoV-2 and megakaryocytes that alters the platelet transcriptome and platelet activity. COVID-19 platelets are hyperreactive and have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. We find transcriptomic changes mediated by SARS-CoV-2 do not occur following exposure of megakaryocytes with a coronavirus responsible for the common cold, CoV-OC43. In a cohort of 3,915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication use, and biomarkers of inflammation and thrombosis, platelet count, size, and immaturity are each associated with increased critical illness and all-cause mortality. Conclusions: Our findings demonstrate that SARS-CoV-2 virions invade megakaryocytes and platelets, inducing alterations to the platelet transcriptome and activation profile, which correlate with critical illness and mortality in hospitalized COVID-19 patients.