Retrospective Clinical Investigation into the Association Between Abnormal Blood Clotting, Oral Anticoagulant Therapy, and Medium-Term Mortality in a Cohort of COVID-19 Patients

<b>Background/Objectives:</b> People affected by COVID-19 are exposed to abnormal clotting and endothelial dysfunction, which may trigger thromboembolic events. This study aimed at retrospectively investigating whether oral anticoagulant therapy (OAT), encompassing either direct oral anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, could have impacted medium-term mortality in a cohort of SARS-CoV-2 patients. <b>Methods:</b> Among 1238 COVID-19 patients, hospitalized from 17 March 2020 to 15 June 2021, 247 survivors and 247 deceased within 90 days from hospitalization were matched 1:1 based on age, sex, and intensive care unit (ICU) admission within three days. Conditional logistic regression was used to estimate associations by means of odds ratio (OR) with a 95% confidence interval (CI). <b>Results:</b> A univariate regression analysis suggested that OAT, no differently from subcutaneous low-molecular-weight heparins (LMWHs) during hospitalization, has no significant impact (<i>p</i> value > 0.05) on medium-term mortality. A multivariate analysis, limited to baseline variables (i.e., comorbidities and pharmacotherapies at hospital admission) showing significant association (<i>p</i> < 0.05) to mortality in a univariate analysis, revealed that, compared to patients living at 90 days from hospitalization, deceased patients had cancer histories (OR 1.75, CI 1.06-2.90, <i>p</i> = 0.029) or suffered from asthma (OR 2.25, CI 1.13-4.47, <i>p</i> = 0.021). In contrast, heart failure (HF), atrial fibrillation (AF), arteriopathy, chronic obstructive pulmonary disease (COPD), and kidney failure (KF), which, in a univariate analysis, were found to be associated with the endpoint (<i>p</i> < 0.05), lost significance in a multivariate analysis. Therapy at admission with aldosterone antagonists also appeared to be associated with medium-term mortality (OR 2.49, CI 1.52-4.08, <i>p</i> < 0.001); whereas, vitamin D supplementation during hospitalization appeared to be beneficial. Although not conclusive, a search into the Eudravigilance database, combined with consulting a digital predictive platform (PLATO, polypharmacology platform prediction), suggested potential off-target activities, which might contribute to increasing the severity of SARS-CoV-2 infection. <b>Conclusions:</b> This retrospective clinical study furnished evidences of the impact of OAT, comorbidities and other pharmacological treatments on COVID-19 clinical course.