MacFadden Derek R, Brown Kevin, Buchan Sarah A, Chung Hannah, Kozak Rob, Kwong Jeffrey C, Manuel Doug, Mubareka Samira, Daneman Nick
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
ICES, Toronto, Ontario, Canada.
Open Forum Infect Dis. 2022 Mar 29;9(5):ofac156. doi: 10.1093/ofid/ofac156. eCollection 2022 May.
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.
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.
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 < .01, adjusted < .01) and β-blockers (weighted OR, 0.87; standard < .01, adjusted = .01), along with individual agents ranging from levetiracetam (weighted OR, 0.70; standard < .01, adjusted < .01) to fluoxetine (weighted OR, 0.86; standard = .013, adjusted = .198) to digoxin (weighted OR, 0.89; standard < .01, adjusted = .02).
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.
对于当前和未来的大流行,都需要高通量药物筛选方法来识别具有潜在预防和/或治疗活性的现有药物。流行病学研究可以补充以实验室为重点的确定可能治疗药物的工作。
我们进行了一项全药典关联研究(PWAS),以确定在2020年1月15日至2020年12月31日期间,加拿大安大略省长期护理机构(LTCHs)和社区中,与≥65岁老年人中严重急性呼吸综合征冠状病毒2(SARS-CoV-2)检测相关的常用处方药和药物类别。
本分析纳入了来自LTCHs和社区的总共26121例病例和2369020例对照。评估的许多药物和药物类别与SARS-CoV-2检测无显著关联。然而,一些药物和药物类别似乎与SARS-CoV-2检测减少显著相关,包括心脏保护药物类别,如他汀类药物(加权比值比[OR],0.91;标准<0.01,调整后<0.01)和β受体阻滞剂(加权OR,0.87;标准<0.01,调整后=0.01),以及从左乙拉西坦(加权OR,0.70;标准<0.01,调整后<0.01)到氟西汀(加权OR,0.86;标准=0.013,调整后=0.198)再到地高辛(加权OR,0.89;标准<0.01,调整后=0.02)等个体药物。
使用这种可应用于当前和未来大流行的流行病学方法,我们确定了多种可能在2019冠状病毒病(COVID-19)中提供治疗益处且可能需要进一步验证的目标药物和药物类别。其中一些药物(如氟西汀)已经因其治疗潜力而被确定。