Impact of vaccination status and anticoagulation on venous thromboembolism risk and outcomes in coronavirus disease 2019 patients

Coronavirus disease 2019 (COVID-19)–related morbidity and mortality is partially associated with major thromboembolic complications triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ The incidence of venous thromboembolism (VTE) has been very high among COVID-19 patients, including both deep vein thrombosis (overall, 20%; intensive care unit [ICU], 28%) and pulmonary embolism (PE; overall, 13%; ICU, 19%), and the associated mortality has been as high as 74%.² The VTE risk can remain elevated for ≤49 weeks after the COVID-19 diagnosis.³

Bozzani et al,⁴ in a retrospective cohort study of patients with moderate to severe COVID-19 infection who had received therapeutic anticoagulation (AC), found that those who had never been vaccinated against SARS-CoV-2 had had a higher risk of VTE, higher mortality rate, and reduced quality of life compared with those who had been fully vaccinated.⁴ Their findings are in line with those from other studies, which have shown that full vaccination against the SARS-CoV-2 carries a protective effect on the risk of VTE in patients with breakthrough infection (hazard ratio, 5.95; 95% confidence interval, 1.82-19.5; interaction P = .02).⁵

Since the first outbreak of the COVID-19 pandemic in January 2022, multiple new variants have emerged, including the Delta variant (B.1.617.2) and the more transmissible and less morbid Omicron variant (B.1.1.529). Vaccination has been shown to be an external intervention that does reduce the risk of COVID-19–associated PE and could explain the decreased rates observed during the Delta and Omicron periods.^{6 , 7}

Bozzani et al⁴ used therapeutic AC for all their patients with moderate to severe COVID-19. The National Institutes of Health guidelines regarding the use of AC therapy for patients with COVID-19 have not been adjusted for the different SARS-CoV-2 variants or patients’ vaccination status. For hospitalized patients, although therapeutic AC will increase the probability of survival to hospital discharge compared with the administration of prophylactic AC for noncritically ill patients, this benefit will disappear for critically ill patients receiving ICU levels of care.⁸

The findings from our daily practice strongly support the hypothesis that the initiation of therapeutic AC after severe COVID-19 has already developed might be too late to alter the detrimental consequences of established COVID-19.^{1 , 8 , 9} Nevertheless, because the long COVID-19 syndrome is considered a constant trigger for thrombosis, patients at high risk of COVID-19–associated VTE with a low bleeding risk might benefit from extending thromboprophylaxis beyond their hospital discharge.^{8 , 9}

The findings that vaccination against the SARS-CoV-2 is safe and carries a low risk of acute VTE after vaccination¹⁰ and that vaccinated patients with COVID-19–associated VTE will have better outcomes and survival than those of unvaccinated patients with COVID-19–associated VTE4, 5, 6, 7 highlights the usefulness of vaccination in the fight against COVID-19. Despite the several limitations of the study by Bozzani et al,⁴ including its retrospective design (which precluded generalizability), the absence of information regarding VTE type, deep vein thrombosis vs PE, VTE severity, timing of therapeutic AC initiation, duration of and compliance with long-term thromboprophylaxis, timing of the episode in relationship to vaccination, the type of SARS-CoV-2 variant responsible for the COVID-19, their findings are in the correct direction regarding the usefulness of vaccination against the SARS-CoV-2.

Further prospective clinical trials are needed to validate the effects of vaccination status, AC intensity and duration, and different SARS-CoV-2 variants on the incidence, severity, and long-term sequelae of COVID-19–associated VTE.