Boston VA Cooperative Studies Program (CSP) Center, VA Boston Healthcare System, Boston, Massachusetts, United States of America.
Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2021 Oct 28;16(10):e0259061. doi: 10.1371/journal.pone.0259061. eCollection 2021.
Effective, low-cost therapeutics are needed to prevent and treat COVID-19. Severe COVID-19 disease is linked to excessive inflammation. Disulfiram is an approved oral drug used to treat alcohol use disorder that is a potent anti-inflammatory agent and an inhibitor of the viral proteases. We investigated the potential effects of disulfiram on SARS-CoV-2 infection and disease severity in an observational study using a large database of clinical records from the national US Veterans Affairs healthcare system. A multivariable Cox regression adjusted for demographic information and diagnosis of alcohol use disorder revealed a reduced risk of SARS-CoV-2 infection with disulfiram use at a hazard ratio of 0.66 (34% lower risk, 95% confidence interval 24-43%). There were no COVID-19 related deaths among the 188 SARS-CoV-2 positive patients treated with disulfiram, in contrast to 5-6 statistically expected deaths based on the untreated population (P = 0.03). Our epidemiological results suggest that disulfiram may contribute to the reduced incidence and severity of COVID-19. These results support carefully planned clinical trials to assess the potential therapeutic effects of disulfiram in COVID-19.
需要有效的、低成本的治疗方法来预防和治疗 COVID-19。严重的 COVID-19 疾病与过度炎症有关。双硫仑是一种已批准用于治疗酒精使用障碍的口服药物，具有很强的抗炎作用和抑制病毒蛋白酶的作用。我们使用美国退伍军人事务部医疗保健系统的大型临床记录数据库进行了一项观察性研究，调查了双硫仑对 SARS-CoV-2 感染和疾病严重程度的潜在影响。多变量 Cox 回归分析调整了人口统计学信息和酒精使用障碍的诊断，结果显示双硫仑的使用降低了 SARS-CoV-2 感染的风险，风险比为 0.66（风险降低 34%，95%置信区间为 24-43%）。在接受双硫仑治疗的 188 名 SARS-CoV-2 阳性患者中，没有 COVID-19 相关死亡病例，而根据未接受治疗的人群，预计会有 5-6 例 COVID-19 相关死亡病例（P = 0.03）。我们的流行病学结果表明，双硫仑可能有助于降低 COVID-19 的发病率和严重程度。这些结果支持精心设计的临床试验，以评估双硫仑在 COVID-19 中的潜在治疗效果。
