Risk Factors for Acute Incident VTE in Ambulatory COVID-19 Patients

Quick Takes

  • Among ambulatory patients with COVID-19 infection, the risk of VTE was markedly higher than those without COVID-19 infection.
  • A history of COVID-19 vaccination significantly reduced the risk of VTE.
  • Patients with inherited thrombophilia had a modestly increased risk of VTE in the post-COVID infection period.

Study Questions:

What is the association between ambulatory coronavirus disease 2019 (COVID-19) and short-term risk of venous thromboembolism (VTE) and the potential protective role of vaccination?


The authors used a population-based cohort study of nonhospitalized patients with and without COVID-19 from a United Kingdom (UK) Biobank between March 1, 2020–September 3, 2021. They propensity-score matched patients with COVID-19 to COVID-19-naïve patients during the same period, excluding those with a history of VTE, use of antithrombotic medications, or those who tested positive during a hospitalization. The primary outcome was a composite of VTE within 30 days of COVID-19 infection, adjusted for age, sex, ethnicity, socioeconomic status, obesity, COVID-19 vaccination status, and history of inherited thrombophilia.


Among 18,818 patients with COVID-19 and 93,179 matched patients without COVID-19, those with an infection had an increased risk of VTE within 30 days of infection (incidence rate 50.99 vs. 2.37 per 1,000 person-years for infected and uninfected patients, respectively; hazard ratio [HR], 21.42; 95% confidence interval [CI], 12.63-36.31). The risk of VTE was attenuated among patients with a history of COVID-19 vaccination (HR, 5.95; 95% CI, 1.82-19.5) as compared to those without COVID-19 vaccination (HR, 27.94; 95% CI, 15.11-51.65; p for interaction = 0.02). Independent predictors of VTE among patients with COVID-19 included older age (HR, 1.87 per 10 years; 95% CI, 1.5-2.33), male sex (HR, 1.69; 95% CI, 1.30-2.19), and obesity (HR, 1.83; 95% CI, 1.15-3.66). Inherited thrombophilia was associated with an increased risk of post-COVID-19 VTE (HR, 2.05; 95% CI, 1.15-3.66).


The authors concluded that ambulatory COVID-19 infection was associated with a substantial risk of VTE. The authors also concluded that COVID-19 vaccination reduced the overall risk of VTE.


This large UK Biobank cohort has two very important findings for clinical practice. First, the markedly elevated risk of VTE among those with ambulatory COVID-19 infection stands in contrast to prior observational studies and meta-analyses. Second, patients who had previously been vaccinated against COVID-19 had a markedly lower risk of VTE than those without COVID-19 vaccination. In fact, prior vaccination status was a larger predictor of VTE risk than age, male sex, and obesity, all of which are well known VTE risk factors. However, the National Heart, Lung, and Blood Institute–funded ACTIV-4B study found very low rates of VTE among ambulatory patients with COVID-19, and no difference with aspirin or anticoagulation therapy as compared to placebo. However, aside from age >40 years, that study population was not enriched for other VTE risk factors and included a markedly smaller number of patients (657) as compared to this cohort study (111,917). While future prospective studies are needed to determine the role of VTE prophylaxis among high-risk patients with ambulatory COVID-19 infection, this study does provide striking evidence that COVID-19 vaccination provides significant protection against VTE risk when an infection occurs.

Clinical Topics: Anticoagulation Management, COVID-19 Hub, Geriatric Cardiology, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Aged, Anticoagulants, COVID-19, COVID-19 Vaccines, Ethnic Groups, Fibrinolytic Agents, Obesity, Primary Prevention, Risk Factors, Social Class, Thrombophilia, Vaccination, Vascular Diseases, Venous Thromboembolism

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