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

Elife. 2021 Jul 27:10:e68165. doi: 10.7554/eLife.68165.

Abstract

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 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.

Keywords: SARS-CoV-2; disease severity; epidemiology; global health; human; infectious disease; microbiology; retrospective study.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage*
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Case-Control Studies
  • Cohort Studies
  • Ezetimibe / administration & dosage
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Rosuvastatin Calcium / administration & dosage
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / physiology
  • Severity of Illness Index
  • Ubiquinone / administration & dosage
  • Vitamin D / administration & dosage
  • Young Adult

Substances

  • Antiviral Agents
  • Ubiquinone
  • Vitamin D
  • Rosuvastatin Calcium
  • Ezetimibe