Cargando…

Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications

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 agent...

Descripción completa

Detalles Bibliográficos
Autores principales: MacFadden, Derek R, Brown, Kevin, Buchan, Sarah A, Chung, Hannah, Kozak, Rob, Kwong, Jeffrey C, Manuel, Doug, Mubareka, Samira, Daneman, Nick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992242/
https://www.ncbi.nlm.nih.gov/pubmed/35531374
http://dx.doi.org/10.1093/ofid/ofac156
_version_ 1784683696489496576
author MacFadden, Derek R
Brown, Kevin
Buchan, Sarah A
Chung, Hannah
Kozak, Rob
Kwong, Jeffrey C
Manuel, Doug
Mubareka, Samira
Daneman, Nick
author_facet MacFadden, Derek R
Brown, Kevin
Buchan, Sarah A
Chung, Hannah
Kozak, Rob
Kwong, Jeffrey C
Manuel, Doug
Mubareka, Samira
Daneman, Nick
author_sort MacFadden, Derek R
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8992242
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-89922422022-04-12 Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications MacFadden, Derek R Brown, Kevin Buchan, Sarah A Chung, Hannah Kozak, Rob Kwong, Jeffrey C Manuel, Doug Mubareka, Samira Daneman, Nick Open Forum Infect Dis Major Article 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. Oxford University Press 2022-03-29 /pmc/articles/PMC8992242/ /pubmed/35531374 http://dx.doi.org/10.1093/ofid/ofac156 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Article
MacFadden, Derek R
Brown, Kevin
Buchan, Sarah A
Chung, Hannah
Kozak, Rob
Kwong, Jeffrey C
Manuel, Doug
Mubareka, Samira
Daneman, Nick
Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications
title Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications
title_full Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications
title_fullStr Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications
title_full_unstemmed Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications
title_short Screening Large Population Health Databases for Potential Coronavirus Disease 2019 Therapeutics: A Pharmacopeia-Wide Association Study of Commonly Prescribed Medications
title_sort screening large population health databases for potential coronavirus disease 2019 therapeutics: a pharmacopeia-wide association study of commonly prescribed medications
topic Major Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992242/
https://www.ncbi.nlm.nih.gov/pubmed/35531374
http://dx.doi.org/10.1093/ofid/ofac156
work_keys_str_mv AT macfaddenderekr screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT brownkevin screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT buchansaraha screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT chunghannah screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT kozakrob screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT kwongjeffreyc screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT manueldoug screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT mubarekasamira screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications
AT danemannick screeninglargepopulationhealthdatabasesforpotentialcoronavirusdisease2019therapeuticsapharmacopeiawideassociationstudyofcommonlyprescribedmedications