Hydrochlorothiazide for COVID-19

 Hydrochlorothiazide has been reported as potentially beneficial for COVID-19 in the following studies.
COVID-19 involves the interplay of 350+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 10,000+ potential treatments. c19early.org analyzes 200+ treatments. We have not reviewed hydrochlorothiazide in detail.
Loucera et al., Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection, Signal Transduction and Targeted Therapy, doi:10.1038/s41392-020-00417-y
Loucera et al., Real-world evidence with a retrospective cohort of 15,968 Andalusian COVID-19 hospitalized patients suggests 21 new effective treatments and one drug that increases death risk., medRxiv, doi:10.1101/2022.08.14.22278751
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. Using data from a central registry of electronic health records (the Andalusian Population Health Database, BPS), the effect of prior consumption of drugs for other indications previous to the hospitalization with respect to patient survival was studied on a retrospective cohort of 15,968 individuals, comprising all COVID-19 patients hospitalized in Andalusia between January and November 2020. 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.
Alamgir et al., Drug repositioning candidates identified using in-silico quasi-quantum molecular simulation demonstrate reduced COVID-19 mortality in 1.5M patient records, medRxiv, doi:10.1101/2021.03.22.21254110
ABSTRACTBackgroundDrug repositioning is a key component of COVID-19 pandemic response, through identification of existing drugs that can effectively disrupt COVID-19 disease processes, contributing valuable insights into disease pathways. Traditional non in silico drug repositioning approaches take substantial time and cost to discover effect and, crucially, to validate repositioned effects.MethodsUsing a novel in-silico quasi-quantum molecular simulation platform that analyzes energies and electron densities of both target proteins and candidate interruption compounds on High Performance Computing (HPC), we identified a list of FDA-approved compounds with potential to interrupt specific SARS-CoV-2 proteins. Subsequently we used 1.5M patient records from the National COVID Cohort Collaborative to create matched cohorts to refine our in-silico hits to those candidates that show statistically significant clinical effect.ResultsWe identified four drugs, Metformin, Triamcinolone, Amoxicillin and Hydrochlorothiazide, that were associated with reduced mortality by 27%, 26%, 26%, and 23%, respectively, in COVID-19 patients.ConclusionsTogether, these findings provide support to our hypothesis that in-silico simulation of active compounds against SARS-CoV-2 proteins followed by statistical analysis of electronic health data results in effective therapeutics identification.