Many drugs, such as Vitamin D, decrease the risk of COVID-19 – July 2021

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
Ariel Israel 1, Alejandro A Schäffer 2, Assi Cicurel 3, Ilan Feldhamer 1, Ameer Tal 1, Kuoyuan Cheng 2, Sanju Sinha 2, Eyal Schiff 4, Gil Lavie 3, Eytan Ruppin 5

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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),
    • (VitaminDWiki has seen hints that it increases vitamin D levels)
  • 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.

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