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

Abstract

Background SARS-Cov-2 is a new virus causing a pandemic of primarily respiratory illness designated as Coronavirus Disease 2019 (COVID-19). This disease is associated with excess mortality, particularly among the elderly, raising concerns for public health. It is crucial to identify whether existing medications could protect against adverse outcomes of COVID-19 infection. Methods We performed a population-based study among members of Clalit Health Services (CHS), the largest healthcare provider in Israel. CHS centrally manages electronic health records (EHR) including medication purchases for over 4.5 million insurees. Since the disease outbreak through October 10, 2020, 8,681 adult patients aged between 18 and 95 have been hospitalized for COVID-19, among them 3,777 in severe condition. Two case-control matched cohorts were assembled to assess which drugs taken by patients in the month preceding a SARS-CoV-2 positive test affected risks of COVID-19 hospitalization and disease severity. Significance of the associations was assessed using Fisher's exact test and Benjamini-Hochberg correction for multiple testing. Findings We identified several drugs and products sold in pharmacies that are significantly associated with reduced odds ratios of SARS-CoV-2 hospitalization and disease severity: notably ubiquinone (OR:0.25, p<0.001), ezetimibe (OR=0.51, P<0.001), rosuvastatin (OR=0.75, p<0.001) and flecainide (OR=0.30, p<0.01). Additionally, acquisition of surgical masks, latex gloves and several ophthalmological products, including eye wipes were associated with decreased risk for hospitalization. Interpretation Ubiquinone, ezetimibe and rosuvastatin, all related to the cholesterol synthesis pathway, are associated with a protective effect against COVID-19 complications. These medications are associated with reduced hospitalization rate and decreased severity in hospitalized patients. These findings set the basis for specific prospective randomized control trials that should be carried out to carefully assess their protective effects.

Statin Use Is Associated with a Decreased Risk of Mortality among Patients with COVID-19

“…We further examined 26 full-text articles and searched the references of relevant articles, retrieving 2 additional publications. Finally, 22 studies met all inclusion criteria [ 1 , 9 , 10 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The flow diagram of the systematic articles search is presented in Figure 1 .…”

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning

“…Analysis of the Clalit Health Care System data warehouse records identified 8,681 adults with SARS-CoV-2 infection and hospitalization in Israel. Simultaneous analysis of linked outpatient pharmacy records identified a reduced likelihood for hospitalization in individuals taking medications known to interact with the cholesterol synthesis pathway, specifically ubiquinone (OR 0.25), ezetimibe (OR 0.51), and rosuvastatin (OR 0.75) in the 30 days prior to diagnosis ( Israel et al., 2020 ).…”

The protective association between statins use and adverse outcomes among COVID-19 patients: a systematic review and meta-analysis

“…All studies were observational in design, with either a retrospective cohort study design or a case-control study design. Israel et al 16 split their database into two cohorts and reported two relative risk ratios for the outcome of mortality. Two studies, Grasselli et al 14 and Rodriguez-Nava et al 20 , reported on ICU patients; the other 11 7-10,13,15-19,21,22 reported on non-ICU patients.…”

“…Two studies, Grasselli et al 14 and Rodriguez-Nava et al 20 , reported on ICU patients; the other 11 7-10,13,15-19,21,22 reported on non-ICU patients. Six studies 7,10,17,18,20,21 defined a statin user as one who used statins after a COVID-19 hospitalization; seven studies 8,9,13-16,19,22 defined a statin user as one who used statins before a COVID-19 hospitalization.…”