Research Service, VA Northern California Health Care System, Martinez, CA, USA.
Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, CA, USA.
Hum Vaccin Immunother. 2022 Dec 31;18(1):1981084. doi: 10.1080/21645515.2021.1981084. Epub 2021 Oct 13.
In the early stages of the COVID-19 global pandemic, caused by the SARS-CoV-2 virus, low- and middle-income countries (LMICs) appeared to be experiencing lower morbidity and mortality rates than high-income countries, particularly the United States. Various suggestions put forward to account for this included the possibility that LMICs might be experiencing off-target benefits of infant vaccination with BCG, intended primarily to protect against tuberculosis. A number of ecologic epidemiological studies that considered COVID-19 morbidity and mortality rates across countries appeared to support this suggestion. Ecologic studies, however, are primarily hypothesis-generating, given their well-known limitations in extrapolating to the individual-person level. The present study, which employed anonymized records of U.S. Military Veterans treated by the Department of Veterans Affairs was principally a case-control study of COVID-19 infections with a retrospective cohort study of mortality nested within the infections. Controls were a random sample of Veterans not recorded as having had COVID-19. There were 263,039 controls and 167,664 COVID-19 cases, of whom 5,016 died. The combination of country and year of birth was used as a surrogate for infant BCG vaccination. The study did not support the hypothesis that BCG in infancy was protective against COVID-19. The odds ratio for infection was 1.07 (95% confidence interval [CI]: 1.03, 1.11) and the risk ratio for mortality among the COVID-19 cases was 0.86 (95% CI: 0.63, 1.18). The potential for non-differential exposure misclassification was a concern, possibly biasing measures of association toward the null value.
在由 SARS-CoV-2 病毒引起的 COVID-19 大流行早期，中低收入国家（LMICs）的发病率和死亡率似乎低于高收入国家，尤其是美国。为了解释这一点，人们提出了各种建议，包括 LMICs 可能因卡介苗（BCG）婴儿接种而获得非目标效益的可能性，卡介苗主要用于预防结核病。一些考虑了各国 COVID-19 发病率和死亡率的生态流行病学研究似乎支持了这一说法。然而，由于其在推断个体水平方面的明显局限性，生态研究主要是假设生成的。本研究利用美国退伍军人事务部治疗的退伍军人匿名记录，主要是一项 COVID-19 感染的病例对照研究，以及嵌套在感染中的死亡率回顾性队列研究。对照组是未记录有 COVID-19 感染的退伍军人的随机样本。有 263,039 名对照和 167,664 名 COVID-19 病例，其中 5,016 人死亡。出生国和年份的组合被用作婴儿 BCG 接种的替代指标。该研究不支持婴儿期 BCG 对 COVID-19 具有保护作用的假设。感染的优势比为 1.07（95%置信区间[CI]：1.03，1.11），COVID-19 病例的死亡率风险比为 0.86（95%CI：0.63，1.18）。非差异暴露错误分类的可能性是一个关注点，可能会使关联措施偏向于零值。
