Marked factor V activity elevation in severe COVID‐19 is associated with venous thromboembolism

Stefely, Jonathan A.; Christensen, Bianca B.; Gogakos, Tasos; Cone Sullivan, Jensyn K.; Montgomery, Gabriella G.; Barranco, John P.; Van Cott, Elizabeth M.

Coagulopathy causes morbidity and mortality in patients with Coronavirus Disease 2019 (COVID‐19) due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) infection. Yet, the mechanisms are unclear and biomarkers are limited. Early in the pandemic, we observed markedly elevated factor V activity in a patient with COVID‐19, which led us to measure factor V, VIII, and X activity in a cohort of 102 consecutive inpatients with COVID‐19. Contemporaneous SARS‐CoV‐2‐negative controls (n = 17) and historical pre‐pandemic controls (n = 260–478) were also analyzed. This cohort represents severe COVID‐19 with high rates of ventilator use (92%), line clots (47%), deep vein thrombosis or pulmonary embolism (DVT/PE) (23%), and mortality (22%). Factor V activity was significantly elevated in COVID‐19 (median 150 IU/dL, range 34–248 IU/dL) compared to contemporaneous controls (median 105 IU/dL, range 22–161 IU/dL) (P < 0.00001)—the strongest association with COVID‐19 of any parameter studied, including factor VIII, fibrinogen, and D‐dimer. Patients with COVID‐19 and factor V activity >150 IU/dL exhibited significantly higher rates of DVT/PE (16/49, 33%) compared to those with factor V activity ≤150 IU/dL (7/53, 13%) (P = 0.03). Within this severe COVID‐19 cohort, factor V activity associated with SARS‐CoV‐2 viral load in a sex‐dependent manner. Subsequent decreases in factor V were linked to progression toward DIC and mortality. Together, these data reveal marked perturbations of factor V activity in severe COVID‐19, provide links to SARS‐CoV‐2 disease biology and clinical outcomes, and nominate a candidate biomarker to investigate for guiding anticoagulation therapy in COVID‐19. This article is protected by copyright. All rights reserved.