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
Carlos Loucera, Rosario Carmona, Marina Esteban-Medina, Gerrit Bostelmann, Dolores Muñoyerro-Muñiz, Román Villegas, María Peña-Chilet, Joaquin Dopazo
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.
Supplementary Material Supplementary Table 1 . Data imported from BPS for each patient: code and definition of the variable. 2 . Log Hazard ratios obtained for the drugs tested, along with standard deviations (SDs), upper and lower coefficient intervals (CI), nominal and FDR-adjusted p-values. Also, Lymphocyte proliferation values (see Methods) along with standard deviations (SDs), upper and lower coefficient intervals (CI), nominal and FDR-adjusted p-values. The two last columns indicate the drugs used in the machine learning drug repurposing prediction study 10 and the significance of the prediction.
Supplementary Table
References
Benjamini, Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society. Series B
Corrigan-Curay, Sacks, Woodcock, Real-World Evidence and Real-World Data for Evaluating Drug Safety and Effectiveness, JAMA : the journal of the American Medical Association,
doi:10.1001/jama.2018.10136
Cowie, Electronic health records to facilitate clinical research, Clinical Research in Cardiology
Greifer, Cobalt, Covariate Balance Tables and Plots
Greifer, Weightit, Weighting for Covariate Balance in Observational Studies
Gutiérrez-Gutiérrez, Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study, The Lancet infectious diseases,
doi:10.1016/S1473-3099(21)00019-0
Hajage, Closed-form variance estimator for weighted propensity score estimators with survival outcome, Biometrical Journal
Hajage, Hripw, Hazard Ratio Estimation using Cox Model Weighted by the Estimated Propensity Score
Hannan, Randomized clinical trials and observational studies: guidelines for assessing respective strengths and limitations, JACC: Cardiovascular Interventions
Hoertel, Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study, Molecular psychiatry
Huang, COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study, Hypertension Research
Imbens, Nonparametric estimation of average treatment effects under exogeneity: A review, Review of Economics and statistics
Kouhpeikar, Statin Use in COVID-19 Hospitalized Patients and Outcomes: A Retrospective Study, Frontiers in Cardiovascular Medicine
Kuznetsova, Brockhoff, Christensen, lmerTest package: tests in linear mixed effects models, Journal of statistical software
Loucera, 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, Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients, Scientific reports
Lu, Prognostic value of lymphocyte count in severe COVID-19 patients with corticosteroid treatment, Signal transduction and targeted therapy
Manenti, Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study, PLOS ONE,
doi:10.1371/journal.pone.0248276
Muñoyerro-Muñiz, Health record linkage: Andalusian health population database, Gaceta Sanitaria
Ostaszewski, COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms, Molecular Systems Biology,
doi:10.15252/msb.202110387
Pawlowski, Enoxaparin is associated with lower rates of mortality than unfractionated Heparin in hospitalized COVID-19 patients, EClinicalMedicine
Rian, Mechanistic modeling of the SARS-CoV-2 disease map, BioData mining
Sherman, Real-world evidence-what is it and what can it tell us, N Engl J Med
Sterne, Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis, JAMA : the journal of the American Medical Association
Stuart, Lee, Leacy, Prognostic score-based balance measures can be a useful diagnostic for propensity score methods in comparative effectiveness research, Journal of clinical epidemiology
Teixeira, Simvastatin Downregulates the SARS-CoV-2-Induced Inflammatory Response and Impairs Viral Infection Through Disruption of Lipid Rafts, Frontiers in Immunology
Umakanthan, The protective role of statins in COVID-19 patients: a retrospective observational study, Transl Med Commun,
doi:10.1186/s41231-021-00102-4
Wood, Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource
Zhou, Liao, Pleiotropic effects of statins. -Basic research and clinical perspectives, Circulation journal : official journal of the Japanese Circulation Society,
doi:10.1253/circj.cj-10-0110