Megakaryocytes are a Novel SARS-CoV-2 Infection Target and Risk Factor for Mortality and Multi-Organ Failure

Discovery of a biomarker for patients at high risk of progression to severe Coronavirus Disease 2019 (COVID-19) is critical for clinical management, particularly in areas of the world where widespread vaccine distribution and herd immunity have yet to be achieved. Herein, we characterize peripheral blood from 218 COVID-19 patients with flow cytometry and provide evidence that megakaryocytes are a target for infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We demonstrate a positive correlation between infected megakaryocytes expressing the protein calprotectin (also called S100A8/A9), a known marker of COVID-19 severity. Additionally, we show that infected, calprotectin expressing megakaryocytes are correlated with COVID-19 severity and are a prognostic indicator of 30-day clinical outcomes including respiratory failure, thrombotic events, acute kidney injury (AKI), ICU admission, and mechanical ventilation. These findings represent a novel SARS-CoV-2 infection target with significant clinical implications as a biomarker for clinical outcomes associated with severe COVID-19.