Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications

{ 'indexed': {'date-parts': [[2022, 3, 30]], 'date-time': '2022-03-30T04:04:47Z', 'timestamp': 1648613087462}, 'reference-count': 0, 'publisher': 'Oxford University Press (OUP)', 'license': [ { 'start': { 'date-parts': [[2022, 3, 29]], 'date-time': '2022-03-29T00:00:00Z', 'timestamp': 1648512000000}, 'content-version': 'am', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by-nc-nd/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, '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 (&amp;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 ' '&amp;lt;0.01, adjusted p-value &amp;lt;0.01) and beta-blockers (weighted OR 0.87, standard ' 'p-value &amp;lt;0.01, adjusted p-value 0.01), along with individual agents ranging from ' 'levetiracetam (weighted OR 0.70, standard p-value &amp;lt;0.01, adjusted p-value ' '&amp;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 &amp;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>', 'DOI': '10.1093/ofid/ofac156', 'type': 'journal-article', 'created': {'date-parts': [[2022, 3, 29]], 'date-time': '2022-03-29T23:20:55Z', 'timestamp': 1648596055000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A ' 'Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications', 'prefix': '10.1093', 'author': [ { 'given': 'Derek R', 'family': 'MacFadden', 'sequence': 'first', 'affiliation': [ { 'name': 'The Ottawa Hospital Research Institute, Clinical Epidemiology ' 'Program, Ottawa, Canada'}, {'name': 'ICES, Toronto, Ontario, Canada'}]}, { 'given': 'Kevin', 'family': 'Brown', 'sequence': 'additional', 'affiliation': [ { 'name': 'Dalla Lana School of Public Health, University of Toronto, ' 'Canada'}, {'name': 'Public Health Ontario, Toronto, Canada'}, {'name': 'ICES, Toronto, Ontario, Canada'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5286-8974', 'authenticated-orcid': False, 'given': 'Sarah A', 'family': 'Buchan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Dalla Lana School of Public Health, University of Toronto, ' 'Canada'}, {'name': 'Public Health Ontario, Toronto, Canada'}, {'name': 'ICES, Toronto, Ontario, Canada'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9463-3591', 'authenticated-orcid': False, 'given': 'Hannah', 'family': 'Chung', 'sequence': 'additional', 'affiliation': [{'name': 'ICES, Toronto, Ontario, Canada'}]}, { 'given': 'Rob', 'family': 'Kozak', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Family and Community Medicine, University of ' 'Toronto, Canada'}, {'name': 'Sunnybrook Research Institute, Toronto, Ontario, Canada'}]}, { 'given': 'Jeffrey C', 'family': 'Kwong', 'sequence': 'additional', 'affiliation': [ { 'name': 'Dalla Lana School of Public Health, University of Toronto, ' 'Canada'}, {'name': 'Public Health Ontario, Toronto, Canada'}, {'name': 'ICES, Toronto, Ontario, Canada'}, { 'name': 'Department of Family and Community Medicine, University of ' 'Toronto, Canada'}]}, { 'given': 'Doug', 'family': 'Manuel', 'sequence': 'additional', 'affiliation': [ { 'name': 'The Ottawa Hospital Research Institute, Clinical Epidemiology ' 'Program, Ottawa, Canada'}, {'name': 'ICES, Toronto, Ontario, Canada'}]}, { 'given': 'Samira', 'family': 'Mubareka', 'sequence': 'additional', 'affiliation': [ {'name': 'Sunnybrook Research Institute, Toronto, Ontario, Canada'}, { 'name': 'Sunnybrook Health Sciences Centre, University of Toronto, ' 'Toronto, Ontario, Canada'}]}, { 'given': 'Nick', 'family': 'Daneman', 'sequence': 'additional', 'affiliation': [ {'name': 'Public Health Ontario, Toronto, Canada'}, {'name': 'ICES, Toronto, Ontario, Canada'}, {'name': 'Sunnybrook Research Institute, Toronto, Ontario, Canada'}, { 'name': 'Sunnybrook Health Sciences Centre, University of Toronto, ' 'Toronto, Ontario, Canada'}]}], 'member': '286', 'published-online': {'date-parts': [[2022, 3, 29]]}, 'container-title': 'Open Forum Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/ofid/advance-article-pdf/doi/10.1093/ofid/ofac156/43152161/ofac156.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/ofid/advance-article-pdf/doi/10.1093/ofid/ofac156/43152161/ofac156.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 3, 29]], 'date-time': '2022-03-29T23:20:56Z', 'timestamp': 1648596056000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 3, 29]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.1093/ofid/ofac156', 'relation': {}, 'ISSN': ['2328-8957'], 'subject': ['Infectious Diseases', 'Oncology'], 'published': {'date-parts': [[2022, 3, 29]]}}