Vaccination Status May Affect Venous Thromboembolism Risk in Ambulatory COVID-19

Among vaccinated individuals, the risk for venous thromboembolism risk was lower in breakthrough COVID-19 cases compared with unvaccinated individuals.

Ambulatory COVID-19 is associated with a substantial increase in excess venous thromboembolism (VTE), which is substantially higher among unvaccinated individuals, and increases with older age, in men, and in patients with obesity. These are the findings of a retrospective study published in JAMA Internal Medicine.

Researchers conducted a population-based cohort study to explore the clinical and genetic risk factors for the development of post–COVID-19 VTE. They also investigated the association between ambulatory COVID-19 and short-term risk for VTE and examined the potential protective role played by vaccination in these individuals.

The current study included participants in England from the UK Biobank who were alive on March 1, 2020. All participants comprised patients with SARS-CoV-2 infection that was confirmed by a positive polymerase chain reaction (PCR) test between March 1, 2020, and September 30, 2021, who were then propensity-score matched to COVID-19–naïve individuals during the same time period. All individuals with a history of VTE who used antithrombotic drugs (1 year prior to the index dates) or tested positive for COVID-19 in the hospital were excluded from the study.

The primary study outcome was a composite of VTE, including deep vein thrombosis or pulmonary embolism, which was reported 30 days following COVID-19 infection. All eligible study participants were followed up for 30 days after the index date, since VTE that occurred after 30 days was much less likely to be linked to a SARS-CoV-2 infection.

This risk was much higher among unvaccinated individuals and increased with older age, in men, and in patients with obesity.

Among a total of 407,311 participants from the UK Biobank, 26,210 had COVID-19 during the study period. Following application of exclusion criteria, 83.0% (21,724 of 26,210) of infected individuals and 83.6% (317,943 of 380,398) of noninfected individuals were eligible for analysis. Among all of the SARS-CoV-2 infections, 2877 and 18,847 were tested in hospital and outpatient settings, respectively, with only the latter included in the subsequent analysis.

Results of the study showed that among 18,818 outpatients with COVID-19 (mean age, 64.3±8.0 years; 10,580 women) and 93,179 matched uninfected participants (mean age, 64.3±7.0 years; 52,177 women), the presence of SARS-CoV-2 infection was associated with an increased risk for VTE in 30 days (incidence rates of 50.99 and 2.37 per 1000 person-years in infected and uninfected individuals, respectively; hazard ratio [HR], 21.42; 95% CI, 12.63-36.31).

The risk for VTE was significantly attenuated, however, among fully vaccinated individuals (HR, 5.95; 95% CI, 1.82-19.50; P =.02). Among participants with
COVID-19, older age (adjusted HR [aHR] per 10 years, 1.87; 95% CI, 1.50- 2.33),

male sex (aHR, 1.69; 95% CI, 1.30-2.19), and obesity (aHR, 1.83; 95% CI, 1.28-2.61), all were independently associated with a higher risk for VTE.

With respect to genetic risk factors, participants with inherited thrombophilia had a higher risk for VTE following a SARS-CoV-2 infection compared with those without the condition (aHR, 2.05; 95% CI, 1.15-3.66). For each risk variant, the aHRs were 2.17 (95% CI, 1.13-4.15) for factor V Leiden carriers and 1.52 (95% CI, 0.48- 4.79) for prothrombin G20210A carriers.

Overall, the researchers found that ambulatory patients with COVID-19 had a higher risk for VTE. “This risk was much higher among unvaccinated individuals and increased with older age, in men, and in patients with obesity,” the researchers stated.

The researchers concluded that the findings from the current study “call for targeted prevention and tailored thromboprophylaxis strategies for post–COVID-19 VTE in outpatient settings and suggest an etiological role of inherited thrombophilia.”

Several limitations of the current study warrant mention. Residual confounding cannot be excluded in this observational analysis, although robust statistical approaches for causal inference were applied. Further, the study was performed in an antithrombotic use–naïve population, as well as prior to the availability of monoclonal antibody infusions and antiviral agents. It remains unclear whether these treatments can mitigate ambulatory COVID-19–related VTE risk.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

References:

Xie J, Prats-Uribe A, Feng Q, et al. Clinical and genetic risk factors for acute incident venous thromboembolism in ambulatory patients with COVID-19. JAMA Intern Med. Published online August 18, 2022. doi:10.1001/jamainternmed.2022.3858