Background Conflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity. Methods We undertook large-scale observational and Mendelian randomisation (MR) analyses using UK Biobank. Most recent smoking status was determined from primary care records (70.8%) and UK Biobank questionnaire data (29.2%). COVID-19 outcomes were derived from Public Health England SARS-CoV-2 testing data, hospital admissions data, and death certificates (until 18 August 2020). Logistic regression was used to estimate associations between smoking status and confirmed SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death. Inverse variance-weighted MR analyses using established genetic instruments for smoking initiation and smoking heaviness were undertaken (reported per SD increase). Results There were 421 469 eligible participants, 1649 confirmed infections, 968 COVID-19-related hospitalisations and 444 COVID-19-related deaths. Compared with never-smokers, current smokers had higher risks of hospitalisation (OR 1.80, 95% CI 1.26 to 2.29) and mortality (smoking 1–9/day: OR 2.14, 95% CI 0.87 to 5.24; 10–19/day: OR 5.91, 95% CI 3.66 to 9.54; 20+/day: OR 6.11, 95% CI 3.59 to 10.42). In MR analyses of 281 105 White British participants, genetically predicted propensity to initiate smoking was associated with higher risks of infection (OR 1.45, 95% CI 1.10 to 1.91) and hospitalisation (OR 1.60, 95% CI 1.13 to 2.27). Genetically predicted higher number of cigarettes smoked per day was associated with higher risks of all outcomes (infection OR 2.51, 95% CI 1.20 to 5.24; hospitalisation OR 5.08, 95% CI 2.04 to 12.66; and death OR 10.02, 95% CI 2.53 to 39.72). Interpretation Congruent results from two analytical approaches support a causal effect of smoking on risk of severe COVID-19. Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. The individual participant data from UK Biobank is available on application by bona fide researchers to the UK Biobank (via the Access Management Team). Individual level data is not permitted to be shared by the authorship team. A data dictionary defining ICD-10 codes used to define comorbidities, or Read/SNOMED codes to define smoking exposures from primary care data, can be made available on request to the corresponding author.

中文翻译：

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吸烟和 COVID-19 结果：使用英国生物银行队列进行的观察性孟德尔随机研究


背景 关于吸烟与 COVID-19 风险及其严重程度的相关性，存在相互矛盾的证据。方法 我们利用英国生物银行进行了大规模观察和孟德尔随机化 (MR) 分析。最近的吸烟状况是根据初级保健记录（70.8%）和英国生物银行问卷数据（29.2%）确定的。 COVID-19 结果源自英国公共卫生部 SARS-CoV-2 检测数据、入院数据和死亡证明（截至 2020 年 8 月 18 日）。 Logistic 回归用于估计吸烟状况与确诊的 SARS-CoV-2 感染、COVID-19 相关住院治疗和 COVID-19 相关死亡之间的关联。使用已建立的遗传工具对吸烟起始和吸烟严重程度进行了反方差加权 MR 分析（按 SD 增加进行报告）。结果共有 421 469 名符合条件的参与者、1649 例确诊感染者、968 例与 COVID-19 相关的住院患者和 444 例与 COVID-19 相关的死亡。与从不吸烟者相比，目前吸烟者的住院风险（OR 1.80，95% CI 1.26 至 2.29）和死亡风险更高（每天吸烟 1-9 支：OR 2.14，95% CI 0.87 至 5.24；每天 10-19 支： OR 5.91，95% CI 3.66 至 9.54；20+/天：OR 6.11，95% CI 3.59 至 10.42）。在对 281 105 名英国白人参与者进行的 MR 分析中，基因预测的开始吸烟倾向与较高的感染风险（OR 1.45，95% CI 1.10 至 1.91）和住院风险（OR 1.60，95% CI 1.13 至 2.27）相关。从基因角度预测，每天吸烟数量较多与所有结局的风险较高相关（感染 OR 2.51，95% CI 1.20 至 5.24；住院 OR 5.08，95% CI 2.04 至 12.66；死亡 OR 10.02，95% CI 2.53 至 12.66）。 39.72）。 两种分析方法得出的一致结果支持吸烟对严重 COVID-19 风险的因果影响。数据可根据合理要求提供。数据可能从第三方获得，并且不公开。英国生物银行的个人参与者数据可通过真正的研究人员向英国生物银行申请（通过访问管理团队）获得。作者团队不允许共享个人级别的数据。可以根据相应作者的要求提供定义用于定义合并症的 ICD-10 代码的数据字典，或用于定义初级保健数据中吸烟暴露的 Read/SNOMED 代码。