Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications
MD, ScD Derek R Macfadden, Kevin Brown, Sarah A Buchan, Hannah Chung, Rob Kozak, Jeffrey C Kwong, Doug Manuel, Samira Mubareka, Nick Daneman
Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156
Background. For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventive and/or therapeutic activity. Epidemiologic studies could complement laboratory-focused efforts to identify possible therapeutic agents. Methods. We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older individuals (≥65 years) in long-term care homes (LTCHs) and the community, between 15 January 2020 and 31 December 2020, across the province of Ontario, Canada. Results. A total of 26 121 cases and 2 369 020 controls from LTCHs and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared to be significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted odds ratio [OR], 0.91; standard P < .01, adjusted P < .01) and β-blockers (weighted OR, 0.87; standard P < .01, adjusted P = .01), along with individual agents ranging from levetiracetam (weighted OR, 0.70; standard P < .01, adjusted P < .01) to fluoxetine (weighted OR, 0.86; standard P = .013, adjusted P = .198) to digoxin (weighted OR, 0.89; standard P < .01, adjusted P = .02). Conclusions. Using this epidemiologic approach, which can be applied to current and future pandemics, we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in coronavirus disease 2019 (COVID-19) and may warrant further validation. Some of these agents (eg, fluoxetine) have already been identified for their therapeutic potential.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Disclaimer. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding sources. No endorsement by ICES, the Ontario Ministry of Health (MOH), or the Ontario Ministry of Long-Term Care (MLTC) is intended or should be inferred.
Notes Financial support. This work was supported by the COVID-19 Emergency Response Fund from The Ottawa Hospital. This study was also supported by ICES, which is funded by an annual grant from the MOH and MLTC. We thank IQVIA Solutions Canada Inc for use of their Drug Information Database. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventative and/or therapeutic activity. Epidemiologic studies could complement lab-focused efforts to identify possible therapeutic agents.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of SARS-CoV-2 in older individuals (&gt;65 years) in long-term care homes (LTCH) and the community, between January 15 th, 2020 and December 31 st, 2020, across the province of Ontario, Canada.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>26,121 cases and 2,369,020 controls from LTCH and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted OR 0.91, standard p-value &lt;0.01, adjusted p-value &lt;0.01) and beta-blockers (weighted OR 0.87, standard p-value &lt;0.01, adjusted p-value 0.01), along with individual agents ranging from levetiracetam (weighted OR 0.70, standard p-value &lt;0.01, adjusted p-value &lt;0.01) to fluoxetine (weighted OR 0.86, standard p-value 0.013, adjusted p-value 0.198) to digoxin (weighted OR 0.89, standard p-value &lt;0.01, adjusted p-value 0.02).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>Using this epidemiologic approach which can be applied to current and future pandemics we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in COVID-19 and may warrant further validation. Some of these agents (e.g. fluoxetine) have already been identified for their therapeutic potential.</jats:p>\n </jats:sec>",
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