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

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 the oral anticoagulant therapy (OAT), encompassing either direct oral anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, may impact on the medium-term mortality in a large cohort of SARS-CoV-2 patients. Among 1238 COVID-19 patients, hospitalized from March 17, 2020, to June 15, 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 95% confidence interval. Compared to patients living at 90 days, those who suffer a fatal event achieved more frequently heart failure, HF (10.5% vs 23.1%; p < 0.001), atrial fibrillation, AF (13.4% vs 22.3%; p = 0.009), as well as respiratory disease or chronic obstructive pulmonary disease (COPD), and renal failure. While HF and AF emerged as the comorbidities mainly associated to medium-term mortality of COVID-19, patients in OAT, no differently from those treated with subcutaneous low-molecular weight heparins (LMWHs) during hospitalization, did not show any significant impact on mortality. In contrast, quite surprisingly, the use of canrenone as mineralcorticoid receptor antagonist in antihypertensive therapy, appeared to worsen the clinical course of COVID-19 patients, whereas vitamin D supplementation showed beneficial effects. The use of a digital predictive platform (PLATO, Polypharmacology pLATform predictiOn) and search into the Eudravigilance database suggested potential associated off-target drug activities, such as modulation of A3 adenosine receptor, and to postulate how aldosterone antagonists might contribute to increase severity of SARS-CoV-2 infection.