Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population

DOI record: { "DOI": "10.7554/elife.68165", "ISSN": [ "2050-084X" ], "URL": "http://dx.doi.org/10.7554/eLife.68165", "abstract": "<jats:sec id=\"abs1\"><jats:title>Background:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id=\"abs2\"><jats:title>Methods:</jats:title><jats:p>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 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.</jats:p></jats:sec><jats:sec id=\"abs3\"><jats:title>Results:</jats:title><jats:p>Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], p&lt;0.001), ezetimibe (OR=0.488, 95% CI [0.377 to 0.622], p&lt;0.001), rosuvastatin (OR=0.673, 95% CI [0.596 to 0.758], p&lt;0.001), flecainide (OR=0.301, 95% CI [0.118 to 0.641], p&lt;0.001), and vitamin D (OR=0.869, 95% CI [0.792 to 0.954], p&lt;0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization.</jats:p></jats:sec><jats:sec id=\"abs4\"><jats:title>Conclusions:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id=\"abs5\"><jats:title>Funding:</jats:title><jats:p>This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.</jats:p></jats:sec>", "alternative-id": [ "10.7554/eLife.68165" ], "assertion": [ { "group": { "name": "peer_review_taxonomy" }, "label": "Peer review transparency", "name": "peer_review_transparency", "value": "single anonymised" }, { "group": { "name": "peer_review_taxonomy" }, "label": "Peer review interaction", "name": "peer_review_interaction", "value": "other reviewer(s), editor" }, { "group": { "name": "peer_review_taxonomy" }, "label": "Peer review published", "name": "peer_review_published", "value": "review summaries, review reports, author/editor communication, reviewer identities reviewer opt in, editor identities" }, { "group": { "name": 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"Cicurel", "given": "Assi", "sequence": "additional" }, { "affiliation": [ { "name": "Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, United States" } ], "family": "Cheng", "given": "Kuoyuan", "sequence": "additional" }, { "affiliation": [ { "name": "Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, United States" } ], "family": "Sinha", "given": "Sanju", "sequence": "additional" }, { "affiliation": [ { "name": "Sheba Medical Center, Tel-Aviv University, Ramat Gan, Israel" } ], "family": "Schiff", "given": "Eyal", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel" } ], "family": "Feldhamer", "given": "Ilan", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Planning and Strategy, Clalit Health Services, Tel Aviv, Israel" } ], "family": "Tal", "given": "Ameer", "sequence": 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