Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
- Clalit Health Services, Israel
- National Institutes of Health, United States
- Sheba Medical Center, Israel
- Tel-Aviv University, Israel
Abstract
Background: Until 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. Towards 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 18-95 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 non-hospitalized 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 multiple testing.
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 National Institutes of Health, NCI.
Data availability
Data were obtained from patients' electronic health records, and IRB approval restrains its use to researchers inside Clalit Health Services. For further information regarding data availability, researchers may contact Dr. Lavie gillav@clalit.org.ilThis study is based on real-world patient drug purchases, and it cannot be made available due to patient privacy concerns. R code used to produce Figure 1 is available as Supplemental File 1.
Article and author information
Author details
Funding
National Cancer Institute (Intramural funding)
- Alejandro A Schäffer
- Kuoyuan Cheng
- Sanju Sinha
- Eytan Ruppin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Frank L van de Veerdonk, Radboudumc Center for Infectious Diseases, Netherlands
Ethics
Human subjects: This study has been approved by the CHS Institutional Review Board (IRB) with a waiver of informed consent, approval number: COM-0046-20.
Version history
- Preprint posted: October 14, 2020 (view preprint)
- Received: March 7, 2021
- Accepted: July 7, 2021
- Accepted Manuscript published: July 27, 2021 (version 1)
- Version of Record published: July 29, 2021 (version 2)
Copyright
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.
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Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
eLife 10:e68165.
https://doi.org/10.7554/eLife.68165
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