Senior author William T. Bain said the findings may explain why some non-ICU patients, including people in their 40s and 50s, suffered strokes, heart attacks or pulmonary embolisms even as lung symptoms improved.
Outside experts called the association novel but said causation and relevance in vaccinated populations need further study; Bain said the mechanism could also inform treatment of influenza, RSV and future SARS outbreaks.
With viruses now known to cause fatal clots, can we predict a patient's risk before a sudden stroke?
Are silent microclots from common viruses the hidden cause of long-term fatigue and brain fog?
Elevated Plasma SARS-CoV-2 RNA and Soluble Thrombomodulin Drive Mortality Risk in Hospitalized COVID-19 Patients
Overview
The ACTIV-4a trial in 2026 revealed that SARS-CoV-2 viremia, the presence of virus in the bloodstream, directly damages the blood vessel lining, causing shedding of thrombomodulin (sTM). This loss disrupts natural anticoagulant and immune regulation, leading to uncontrolled clotting, inflammation, and microvascular thrombosis that damage organs and increase death risk. Elevated sTM partly explains this link and serves as a key biomarker. Therapeutic-dose anticoagulation improves survival in moderately ill patients by reducing clot-related complications. Genetic factors influence how severely patients experience endothelial injury. These findings highlight the critical role of endothelial damage in COVID-19 severity and guide targeted treatments and future research.