Estimating the effect of COVID-19 vaccination and infection variant on post-COVID-19 venous thrombosis or embolism risk

Background Previous research has shown that vaccination reduces risk of post–coronavirus disease 2019 (COVID-19) venous thrombosis or embolism (VTE), but the effect of vaccine boosting on post-COVID-19 VTE risk reduction is unclear. We sought to estimate the effect of COVID-19 vaccination on the risk of post-COVID-19 VTE and to examine if the magnitude of this association differed among variant eras. Methods We performed a case-control study of Military Health System (MHS) beneficiaries who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020–2022. Cases were defined as those with medically attended VTE within 90 days after their first positive SARS-CoV-2 test; controls were defined as SARS-CoV-2 infections without incident VTE by 90 days. Multivariate logistic regression estimated the odds of post-SARS-CoV-2 VTE based on pre-COVID-19 vaccine status, adjusting for other VTE risk factors. Results A total of 4646 MHS beneficiaries were included in this analysis; 1370 received a primary vaccine series and a further 790 received at least 1 booster at time of infection; 71 had VTE within 90 days of SARS-CoV-2 infection. Those who were vaccinated had lower odds of VTE (adjusted odds ratio [95% confidence interval]) compared to the unvaccinated following infection (primary series: 0.28 [.13–.62]; booster dose: 0.06 [.01–.46]). Post-COVID-19 VTE risk was lowest during the Omicron era, but VTEs were too rare to examine for an interaction of variant era and vaccine effect. Conclusions Among MHS beneficiaries, COVID-19 vaccination was associated with a reduced risk of post-COVID-19 VTE diagnosis; estimated risk reduction was larger among those who received a booster.