Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments

Abstract

Purpose Despite the extensive vaccination campaigns in many countries, COVID-19 is still a major worldwide health problem because of its associated morbidity and mortality. Therefore, finding efficient treatments as fast as possible is a pressing need. Drug repurposing constitutes a convenient alternative when the need for new drugs in an unexpected medical scenario is urgent, as is the case with COVID-19. Methods Using data from a central registry of electronic health records (the Andalusian Population Health Database), the effect of prior consumption of drugs for other indications previous to the hospitalization with respect to patient outcomes, including survival and lymphocyte progression, was studied on a retrospective cohort of 15,968 individuals, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. Results Covariate-adjusted hazard ratios and analysis of lymphocyte progression curves support a significant association between consumption of 21 different drugs and better patient survival. Contrarily, one drug, furosemide, displayed a significant increase in patient mortality. Conclusions In this study we have taken advantage of the availability of a regional clinical database to study the effect of drugs, which patients were taking for other indications, on their survival. The large size of the database allowed us to control covariates effectively.

Use of drugs for hypertension or heart failure and the risk of death in COVID-19: association with loop-diuretics

“…In the study, which aimed to find effective treatments among drugs used for other indications, 21 drugs out of a total of 864 treatments were found to be associated with improved patient survival, among them hydrochlorothiazide. In contrast, only one drug -the loop-diuretic furosemide -was associated with an increase in patient mortality [31].…”

drexml: A command line tool and Python package for drug repurposing

“…In summary, the drexml package is a modernized version of a drug repurposing approach that was never implemented in software form. Despite its lack of formal software implementation, the methodology was highly successful, resulting in multiple studies [40] , [72] that identified potential drug repurposing candidates through both laboratory [49] , [71] and real-world data [73] , [74] . We expect that the availability of the drexml package will encourage more people to use this methodology, thus expanding the druggable space for various diseases and furthering research in this area.…”

The mechanistic functional landscape of retinitis pigmentosa: a machine learning-driven approach to therapeutic target discovery

“…They have been used to predict candidate essential genes in cancer cell lines, whose further inhibition validated the predictions [ 12 ]. Repurposable drug candidates were proposed for Fanconi Anemia [ 17 ] which were further experimentally validated [ 21 ], and for COVID-19 [ 18 ], also validated using a cohort of around 16,000 patients of the Andalusian healthcare database [ 22 , 23 ]. These computational methods represent a leap in the generation and testing of hypotheses guided by a specific functional rationale, especially useful in scenarios with limited knowledge like rare diseases such as RP.…”