The use of oral anticoagulation at the time of acute COVID-19 infection and subsequent development of long-COVID/post-acute sequelae of SARS-CoV-2 infection.

Long COVID (LC) or post-acute sequelae of SARS-CoV-2 infection (PASC) is defined as ongoing, relapsing or new symptoms/conditions persisting after an acute COVID-19 infection. Given the potential role of oral anticoagulants (OAC) in treating thrombotic sequelae of LC/PASC, we investigated whether prevalent OAC use at the time of acute COVID-19 infection was associated with reduced development of LC/PASC. Retrospective cohort study within the TriNetx network. The primary cohort was defined as adults with a confirmed diagnosis of COVID-19. We defined OAC users as those who had received OACs (either direct-acting OACs [DOACs] or vitamin K antagonists [VKA]) in the preceding 3-months and non-users as those without OAC use within the previous 12-months. The primary outcome was a composite of 9 features associated with LC/PASC We identified 38,409 DOAC users, 19,243 VKA users, and 2,329,771 non-OAC users with acute COVID-19 infection. After successful propensity score matching (PSM), we found an increased risk of LC/PASC features in those receiving DOAC compared to non-OAC (HR [95% CI] 1.50 [1.35 to 1.68], p < 0.0001), and in VKA users compared to non-OACs (HR [95% CI] 1.98 [1.78 to 2.20], p < 0.0001), while DOAC users were at reduced risk compared to VKA users (HR [95% CI] 0.71 [0.62 to 0.81], p < 0.0001). We found no evidence that prevalent OAC at the time of acute COVID-19 infection was associated with reduced risk of LC/PASC. Further work is needed to understand whether there is a role for OAC therapy in the management of LC/PASC.