DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
This study aimed to systematically investigate if any of the available drugs in the electronic health record (EHR) can be repurposed as potential treatment for coronavirus disease 2019 (COVID‐19). Based on a retrospective cohort analysis of EHR data, drug‐wide association studies (DrugWAS) were performed on 9,748 patients with COVID‐19 at Vanderbilt University Medical Center (VUMC). For each drug study, multivariable logistic regression with overlap weighting using propensity score was applied to estimate the effect of drug exposure on COVID‐19 disease outcomes. Patient exposure to a drug between 3‐months prior to the pandemic and the COVID‐19 diagnosis was chosen as the exposure of interest. All‐cause of death was selected as the primary outcome. Hospitalization, admission to the intensive care unit, and need for mechanical ventilation were identified as secondary outcomes. Overall, 17 drugs were significantly associated with decreased COVID‐19 severity. Previous exposure to two types of 13‐valent pneumococcal conjugate vaccines, PCV13 (odds ratio (OR), 0.31, 95% confidence interval (CI), 0.12–0.81 and OR, 0.33, 95% CI, 0.15–0.73), diphtheria toxoid and tetanus toxoid vaccine (OR, 0.38, 95% CI, 0.15–0.93) were significantly associated with a decreased risk of death (primary outcome). Secondary analyses identified several other significant associations showing lower risk for COVID‐19 outcomes: acellular pertussis vaccine, 23‐valent pneumococcal polysaccharide vaccine (PPSV23), flaxseed extract, ethinyl estradiol, estradiol, turmeric extract, ubidecarenone, azelastine, pseudoephedrine, dextromethorphan, omega‐3 fatty acids, fluticasone, and ibuprofen. In conclusion, this cohort study leveraged EHR data to identify a list of drugs that could be repurposed to improve COVID‐19 outcomes. Further randomized clinical trials are needed to investigate the efficacy of the proposed drugs.
Article activity feed
-
-
SciScore for 10.1101/2021.02.04.21251169: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the institutional review board at VUMC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable At VUMC, SARS-CoV-2 PCR testing was initially limited to symptomatic individuals and a selected category of patients who needed to be physically present in a VUMC facility (eg, pregnant women or patients scheduled for surgery) PCR testing was required before their visit. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from Limitat…SciScore for 10.1101/2021.02.04.21251169: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the institutional review board at VUMC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable At VUMC, SARS-CoV-2 PCR testing was initially limited to symptomatic individuals and a selected category of patients who needed to be physically present in a VUMC facility (eg, pregnant women or patients scheduled for surgery) PCR testing was required before their visit. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations: Although overlap weighting with propensity score was applied to balance out the main patient characteristics between the drug exposed and unexposed groups, there may be unmeasured confounding factors that were not included in the propensity score model. Thus, while the bias may be reduced, confounding by indication is still possible due to unmeasured confounding factors. This is a major limitation, generally applicable to observational studies that lack randomization for drug exposure assignment.40,62 Treatment misclassification was addressed by including only patients with at least one encounter in the EHR such that drug exposure information could be extracted for each SARS-CoV-2 positive patient during at least one year prior to diagnosis. However, EHR phenotyping pose many challenges which could lead to inaccurately extracting the treatment status of the patient.63 For example, drug exposure extraction from clinical text relies on accurate identification of text expressions that are negated (eg, “he could not be on Coumadin because of history of GI bleed”) or hypothetical (eg, “Zofran 4 mg PO once a day as needed for nausea”).23,64 This is another reason for interpreting the results of dietary supplements with caution since they are primarily extracted from clinical notes. Furthermore, assuming drug exposure information is accurately extracted for a patient, exposure of the drug at and after diagnosis time is not guaranteed. However, vaccine data in the EHR is...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04263402 Recruiting The Efficacy of Different Hormone Doses in 2019-nCoV Severe … NCT04559113 Recruiting Methylprednisolone in COVID-19 Patients (Methyl19LGH) NCT04636671 Not yet recruiting Methylprednisolone vs. Dexamethasone in COVID-19 Pneumonia (… NCT04334629 Recruiting LIBERATE Trial in COVID-19 NCT04382768 Recruiting Inhaled Ibuprofen to Treat COVID-19 NCT04383899 Recruiting Role of Ibuprofen and Other Medicines on Severity of Coronav… NCT04539626 Not yet recruiting Estrogen Therapy in Non-severe COVID-19 Patients Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from scite Reference Check: We found no unreliable references.
-
