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DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

Bejan et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2376 (date from preprint)
Feb 2021  
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Mortality 34% Improvement Relative Risk Ventilation 25% ICU admission 15% Hospitalization 0% Vitamin C for COVID-19  Bejan et al.  Prophylaxis Is prophylaxis with vitamin C beneficial for COVID-19? Retrospective 9,748 patients in the USA Lower mortality (p=0.33) and ventilation (p=0.47), not sig. c19early.org Bejan et al., Clinical Pharmacology & .., Feb 2021 Favorsvitamin C Favorscontrol 0 0.5 1 1.5 2+
Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020, now with p = 0.00000002 from 73 studies, recognized in 12 countries.
Lower risk for mortality, ICU, hospitalization, and recovery.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
Retrospective 9,748 COVID-19 patients in the USA showing lower risk of mortality, ventilation, and ICU admission with vitamin C prophylaxis, without statistical significance.
This is the 15th of 73 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.00000002 (1 in 50 million).
21 studies are RCTs, which show efficacy with p=0.0012.
Study covers curcumin, aspirin, zinc, vitamin B9, vitamin C, and vitamin B12.
risk of death, 34.0% lower, OR 0.66, p = 0.33, treatment 569, control 8,637, adjusted per study, RR approximated with OR.
risk of mechanical ventilation, 25.0% lower, OR 0.75, p = 0.47, treatment 572, control 8,657, adjusted per study, RR approximated with OR.
risk of ICU admission, 15.0% lower, OR 0.85, p = 0.65, treatment 577, control 8,690, adjusted per study, RR approximated with OR.
risk of hospitalization, no change, OR 1.00, p = 1.00, treatment 626, control 9,122, adjusted per study, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bejan et al., 28 Feb 2021, retrospective, USA, peer-reviewed, mean age 42.0, 6 authors. Contact: adi.bejan@vanderbilt.edu.
This PaperVitamin CAll
DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
Cosmin A Bejan, Katherine N Cahill, Patrick J Staso, Leena Choi, Josh F Peterson, Elizabeth J Phillips
Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2376
Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?  Drug repurposing methodologies have emerged as an attractive strategy to rapidly identify safe and effective treatments for coronavirus disease 2019 (COVID-19). Despite recent advances, widely available treatments that can be used early in a patient's illness to prevent hospitalization, progression to more severe outcomes, and long-term complications have yet to be discovered. WHAT QUESTION DID THIS STUDY ADDRESS?  Can electronic health records be used to search for drug candidates that could be repurposed to treat COVID-19? WHAT DOES THIS STUDY ADD TO OUR KNOW-LEDGE?  The study found 17 drug ingredients that are significantly associated with a decreased risk of death and other severe COVID-19 outcomes. The study suggests that Streptococcus pneumoniae vaccines and diphtheria toxoid and tetanus toxoid vaccine, with or without acellular pertussis vaccine should not be delayed or discontinued due to the COVID-19 pandemic as they may protect the general population from severe acute respiratory syndrome coronavirus 2 infection worldwide. HOW MIGHT THIS CHANGE CLINICAL PHARMA-COLOGY OR TRANSLATIONAL SCIENCE?  The list of drugs proposed by this study could provide additional insights into developing new candidates for COVID-19 treatment.
SUPPORTING INFORMATION Supplementary information accompanies this paper on the Clinical Pharmacology & Therapeutics website (www.cpt-journal.com). CONFLICT OF INTEREST K.N.C. reported personal fees from Teva, personal fees from Optinose, personal fees from Novartis, personal fees from GlaxoSmithKline, personal fees from Blueprint Medicines, personal fees from Third Harmonic Bio, personal fees from Sanofi Pasteur, personal fees from Genentech, personal fees from Regeneron and personal fees from Ribon Therapeutics, outside the submitted work. J.F.P. reported personal fees from Color Genomics outside the submitted work. E.J.P. receives Royalties from UpToDate and consulting fees from Janssen, Vertex, Biocryst, and Regeneron outside of the submitted work. She is co-director of IIID Pty Ltd that holds a patent for HLA-B*57:01 testing for abacavir hypersensitivity, and has a patent pending for Detection of Human Leukocyte Antigen-A*32:01 in connection with Diagnosing Drug Reaction with Eosinophilia and Systemic Symptoms without any financial remuneration and not directly related to the submitted work. All other authors declared no competing interests for this work. AUTHOR CONTRIBUTIONS ROLE OF THE FUNDER/SPONSOR The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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