Effective therapies for COVID-19 are still lacking, and drug repositioning is a promising approach to address this problem. Here, we adopted a medical informatics approach to repositioning. We leveraged a large prospective cohort, the UK-Biobank (UKBB, N ~ 397,000), and studied associations of prior use of all level-4 ATC drug categories (N = 819, including vaccines) with COVID-19 diagnosis and severity. Effects of drugs on the risk of infection, disease severity, and mortality were investigated separately. Logistic regression was conducted, controlling for main confounders. We observed strong and highly consistent protective associations with statins. Many top-listed protective drugs were also cardiovascular medications, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium channel blocker (CCB), and beta-blockers. Some other drugs showing protective associations included biguanides (metformin), estrogens, thyroid hormones, proton pump inhibitors, and testosterone-5-alpha reductase inhibitors, among others. We also observed protective associations by influenza, pneumococcal, and several other vaccines. Subgroup and interaction analyses were also conducted, which revealed differences in protective effects in various subgroups. For example, protective effects of flu/pneumococcal vaccines were weaker in obese individuals, while protection by statins was stronger in cardiovascular patients. To conclude, our analysis revealed many drug repositioning candidates, for example several cardiovascular medications. Further studies are required for validation.

中文翻译：

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探索与 COVID-19 风险和严重程度改变相关的药物和疫苗：英国生物银行对所有 ATC 4 级药物类别进行的队列研究揭示了重新定位的机会

目前仍缺乏针对 COVID-19 的有效疗法，而药物重新定位是解决这一问题的一种有前景的方法。在这里，我们采用了医学信息学方法来重新定位。我们利用大型前瞻性队列 UK-Biobank（UKBB，N ~ 397,000），研究了先前使用所有 4 级 ATC 药物类别（N = 819，包括疫苗）与 COVID-19 诊断和严重程度的关联。分别研究了药物对感染风险、疾病严重程度和死亡率的影响。进行逻辑回归，控制主要混杂因素。我们观察到与他汀类药物有强烈且高度一致的保护关联。许多排名第一的保护药物也是心血管药物，例如血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体阻滞剂（ARB）、钙通道阻滞剂（CCB）和β受体阻滞剂。其他一些显示出保护作用的药物包括双胍类（二甲双胍）、雌激素、甲状腺激素、质子泵抑制剂和睾酮 5-α 还原酶抑制剂等。我们还观察到流感、肺炎球菌和其他几种疫苗的保护作用。还进行了亚组和相互作用分析，揭示了不同亚组中保护作用的差异。例如，流感/肺炎球菌疫苗对肥胖个体的保护作用较弱，而他汀类药物对心血管患者的保护作用较强。总而言之，我们的分析揭示了许多药物重新定位候选药物，例如几种心血管药物。需要进一步研究进行验证。