Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
Israel et al.
, Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large..
, Epidemiology and Global Health Microbiology and Infectious Disease, doi:10.7554/eLife.68165
Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with dutasteride.
risk of hospitalization, 37.7% lower, OR 0.62, p = 0.01, treatment 30 of 6,530 (0.5%) cases,
240 of 32,650 (0.7%) controls, NNT 18, case control OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Israel et al., 27 Jul 2021, retrospective, Israel, peer-reviewed, 10 authors.
Abstract: RESEARCH ARTICLE
Identification of drugs associated with
reduced severity of COVID-19 – a casecontrol study in a large population
Ariel Israel1*, Alejandro A Schäffer2, Assi Cicurel1,3, Kuoyuan Cheng2,
Sanju Sinha2, Eyal Schiff4, Ilan Feldhamer1, Ameer Tal1, Gil Lavie1,5†,
Division of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel; 2Cancer
Data Science Laboratory, National Cancer Institute, National Institutes of Health,
Bethesda, United States; 3Clalit Health Services, Southern District and Faculty of
Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 4Sheba
Medical Center, Tel-Aviv University, Ramat Gan, Israel; 5Ruth and Bruce Rappaport
Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
These authors contributed
equally to this work
Competing interests: The
authors declare that no
competing interests exist.
Funding: See page 12
Received: 07 March 2021
Preprinted: 14 October 2020
Accepted: 07 July 2021
Published: 27 July 2021
Reviewing editor: Frank L van
de Veerdonk, Radboudumc
Center for Infectious Diseases,
This is an open-access article,
free of all copyright, and may be
freely reproduced, distributed,
transmitted, modified, built
upon, or otherwise used by
anyone for any lawful purpose.
The work is made available under
the Creative Commons CC0
public domain dedication.
Background: Until coronavirus disease 2019 (COVID-19) drugs specifically developed to treat
COVID-19 become more widely accessible, it is crucial to identify whether existing medications
have a protective effect against severe disease. Toward this objective, we conducted a large
population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring
over 4.7 million members.
Methods: Two case-control matched cohorts were assembled to assess which medications,
acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were
adults aged 18 to 95 hospitalized for COVID-19. In the first cohort, five control patients, from the
general population, were matched to each case (n=6202); in the second cohort, two nonhospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The
outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence
interval (CI), and the p-value, using Fisher’s exact test. False discovery rate was used to adjust for
Results: Medications associated with most significantly reduced odds for COVID-19 hospitalization
include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], p<0.001), ezetimibe (OR=0.488, 95% CI
[0.377 to 0.622], p<0.001), rosuvastatin (OR=0.673, 95% CI [0.596 to 0.758], p<0.001), flecainide
(OR=0.301, 95% CI [0.118 to 0.641], p<0.001), and vitamin D (OR=0.869, 95% CI [0.792 to 0.954],
p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological
products were also associated with decreased risk for hospitalization.
Conclusions: Ubiquinone, ezetimibe, and rosuvastatin, all related to the cholesterol synthesis
pathway were associated with reduced hospitalization risk. These findings point to a promising
protective effect which should be further investigated in controlled, prospective studies.
Funding: This research was supported in part by the Intramural Research Program of the..
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