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Identifying Drug Repurposing Candidates for COVID-19 Using Drug-Wide Association Studies

A recent study carried out a systematic evaluation of the drugs available in electronic health record data, including prescription drugs and dietary supplements, to identify potential drug repurposing candidates for COVID-19 treatment.

COVID-19 treatment

While significant progress has been made in the development of safe and effective SARS-CoV-2 vaccines, extensive efforts are currently underway to identify treatments that are able to improve COVID-19 outcome, particularly drugs that can be used early in a patient’s illness to prevent hospitalisation and death. Recently, the antiviral drug – remdesivir – has been proven to improve the recovery time of adult patients hospitalised with COVID-19. Monoclonal antibodies have also been shown to reduce the viral load and improve clinical outcomes in outpatients with mild COVID-19. Furthermore, several other drugs including corticosteroids, antiviral therapies and immune modulators, are currently being investigated as potential therapies for COVID-19. However, despite advances, there is an urgent need for the discovery of safe and effective treatments to prevent COVID-19 progression.

Drug-wide associate studies to identify drug repurposing candidates for COVID-19

Since de novo treatments usually take many years to reach the market, involve significant costs, and have a low success rate, drug repurposing methodologies have emerged as an attractive strategy to accelerate the discovery of novel COVID-19 treatments. The researchers behind this study leveraged real-world data from electronic health records (EHRs) to conduct a drug-wide associate study (DrugWAS) to systematically investigate all recorded drug exposures as potential drug repurposing candidates for COVID-19.

DrugWAS is a high-throughput approach for investigating associations between drugs and disease outcomes. It relies on retrospective cohort analysis of the data stored in the Vanderbilt University Medical Center (VUMC) Research Derivative. This research derivative is a daily updated database of identified EHR data. For each drug study, the researchers applied multivariable logistic regression with overlap weighting using propensity score to estimate the effect of drug exposure on COVID-19 disease outcomes. Patient exposure to a drug 1-year prior to the pandemic and COVID-19 diagnosis was chosen as the exposure of interest. Natural language processing was used to extract drug information from clinical notes, as well as the prescription drug data available. In this study all-causes of death was selected as a primary outcome. Whereas, hospitalisation, admission to the intensive care unit and need for mechanical ventilation were identified as a secondary outcome.

Results using DrugWAS to identify drug repurposing candidates for COVID-19

Overall, this study included 7,768 COVID-19 patients, of which 509 were hospitalised, 82 were admitted to the ICU, 64 received mechanical ventilation and 90 died. The researchers identified 15 drugs that were significantly associated with decreased COVID-19 disease severity. Moreover, previous exposure to either Streptococcus pneumoniae vaccines, diphtheria toxoid vaccine and tetanus toxoid vaccine were significantly associated with a decreased risk of death. This finding may be explained by the ability of these vaccines to stimulate the immune system and provide immunologic protection against SARS-CoV-2. Secondary analyses identified several other drugs with significant associations to improved COVID-19 outcomes.

The drugs associated with improved secondary outcomes in COVID-19 patients include:

  1. Acellular pertussis vaccine
  2. Streptococcus pneumoniae vaccine
  3. Dietary supplements (turmeric extract, flaxseed extract, omega-3 fatty acids)
  4. Methylprednisolone acetate
  5. Pseudoephedrine
  6. Ethinyl estradiol
  7. Estradiol
  8. Ibuprofen
  9. Fluticasone

The researchers are not aware of previous research demonstrating that dietary supplements are associated with a reduced COVID-19 severity risk. However, due to their anti-inflammatory properties, researchers have proposed them as alternative treatments to improve clinical outcomes in COVID-19 patients.


This study used DrugWAS to investigate recorded drug exposures outlined in EHR data to identify drug repurposing candidates for COVID-19. The researchers hope that their proposed list of drug ingredients will provide additional insights into developing efficient COVID-19 treatments and will serve as a starting point for future prospective studies. Moreover, since the short- and long-term adverse effects of these drugs have been already studied, their efficacy against COVID-19 could be investigated rapidly in clinical trials.

Image credit: pmvchamara – FreePik

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