COVID-19 Bloodstream Infection Linked to Increased Blood Clot Risk, Suggests Study
USA: New research suggests that COVID-19 patients face a higher risk of heart attack and stroke when the virus spreads into the bloodstream (viremia). Researchers found that clotting risk is associated with elevated levels of soluble thrombomodulin, a marker of blood vessel lining damage. Thrombomodulin normally remains attached to cells lining blood vessels, but during viremia, these proteins detach and become soluble, causing vascular injury that may contribute to dangerous blood clots.
The findings were published in the Journal of the American Heart Association by Benjamin E. Zuchelkowski and colleagues in a study titled Soluble Thrombomodulin Links Viremia and Mortality During COVID‐19.
Although COVID-19 is primarily considered a respiratory illness, previous studies have shown that the infection can also trigger cardiovascular complications, including thrombosis, heart attack, and stroke. Researchers have increasingly focused on the role of SARS-CoV-2 viremia—the presence of viral material in the bloodstream—as a possible contributor to severe disease outcomes.
To investigate this relationship, the researchers analyzed plasma samples from hospitalized COVID-19 patients enrolled in the ACTIV-4a randomized clinical trial evaluating antithrombotic therapy. The team measured SARS-CoV-2 nucleocapsid RNA and protein levels in blood samples and examined their association with biomarkers linked to inflammation, endothelial injury, thrombosis, and mortality.
The study included 93 hospitalized patients with COVID-19. Investigators found that levels of viral RNA and viral nucleocapsid antigen were significantly higher in patients who did not survive. Elevated plasma viral RNA levels were associated with a higher risk of death within 90 days as well as an increased risk of thrombotic events.
The key findings were as follows:
- Viral RNA levels were more accurate than nucleocapsid antigen levels in predicting survival outcomes in hospitalized COVID-19 patients.
- Higher plasma viral RNA levels were associated with elevated soluble thrombomodulin concentrations.
- The findings suggest a link between SARS-CoV-2 viremia and endothelial injury.
- Soluble thrombomodulin is a biomarker of thrombotic endotheliopathy, a condition involving damage to the blood vessel lining that can promote abnormal clot formation.
- Mediation analysis showed that soluble thrombomodulin partly explained the association between viral RNA levels and mortality.
- Soluble thrombomodulin accounted for approximately 12% of the relationship between viral RNA levels and 90-day mortality after adjustment for age and sex.
The researchers suggested that viral spread from the lungs into the bloodstream may contribute to cardiovascular complications by promoting endothelial dysfunction and thrombosis, a mechanism that could also apply to other respiratory viral infections. They acknowledged limitations, including limited biospecimen availability, non-standardized thrombosis screening, and a relatively small number of events.
Overall, the study identified a potential link between SARS-CoV-2 viremia, endothelial injury, and mortality, highlighting the need for further research into therapies targeting viremia or endothelial dysfunction.
Reference:
Zuchelkowski BE, Inman KW, Nouraie SM, Beru N, Naqvi A, Qin S, Yeh CH, Zhang Y, Shah FA, Sharma L, Dela Cruz CS, Zhang L, McVerry BJ, Morris A, Neal MD, Seheult J, Kitsios GD, Mellors JW, Lawrence DA, Kim PY, Jacobs JL, Bain WG. Soluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial. J Am Heart Assoc. 2026 May 6:e047693. doi: 10.1161/JAHA.125.047693. Epub ahead of print. PMID: 42089155.
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