Bacille Calmette-Guerin Vaccination in Infancy Does Not Protect Against Coronavirus Disease 2019 (COVID-19): Evidence From a Natural Experiment in Sweden
Bacille Calmette-Guerin Vaccination in Infancy Does Not Protect Against Coronavirus Disease 2019 (COVID-19): Evidence From a Natural Experiment in Sweden
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DOI：
10.1093/cid/ciaa1223
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发表时间：
2021-05-15
影响因子：
11.8
通讯作者：
de Chaisemartin, Luc
中科院分区：
文献类型：
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作者：
de Chaisemartin, Clement;de Chaisemartin, Luc
背景卡介苗（BCG）结核病疫苗对呼吸道感染有免疫作用。因此，假设其对2019冠状病毒病（COVID-19）具有保护作用。最近的研究发现，实施普遍卡介苗儿童疫苗接种政策的国家往往受COVID-19大流行的影响较小。然而，这样的生态研究是有偏见的许多混杂因素。相反，本文报道了1975年发生在瑞典的一项罕见的全国性自然实验，在该实验中，新生儿BCG疫苗接种的停止导致BCG覆盖率的急剧下降，从而使我们能够在没有与跨国比较相关的偏差的情况下估计BCG的效果。记录了1975年之前和之后出生的出生队列的COVID-19病例和住院人数，分别代表1 026 304和1 018 544人。我们使用回归不连续性来评估卡介苗接种对COVID-19相关结果的影响。在如此大的人群中，这种方法允许使用随机对照试验难以实现的精确度。COVID-19病例和COVID-19相关住院的比值比（95%CI）分别为1.0005（.8130-1.1881）和1.2046（.7532-1.6560），使我们能够拒绝普遍接种BCG疫苗的相当温和的影响。我们可以以95%的置信度拒绝普遍接种BCG疫苗将病例数减少19%，住院人数减少25%。虽然必须评估最近接种疫苗的效果，但我们提供了强有力的证据，证明出生时接种卡介苗对中年人的COVID-19没有保护作用。
Background. The bacille Calmette-Guerin (BCG) tuberculosis vaccine has immunity benefits against respiratory infections. Accordingly, it has been hypothesized to have a protective effect against coronavirus disease 2019 (COVID-19). Recent research found that countries with universal BCG childhood vaccination policies tend to be less affected by the COVID-19 pandemic. However, such ecological studies are biased by numerous confounders. Instead, this paper reports on a rare nationwide natural experiment that occurred in Sweden in 1975, where discontinuation of newborns' BCG vaccination led to a dramatic decrease in BCG coverage rate, thus allowing us to estimate BCG's effect without the biases associated with cross-country comparisons.Methods. Numbers of COVID-19 cases and hospitalizations were recorded for birth cohorts born just before and just after 1975, representing 1 026 304 and 1 018 544 individuals, respectively. We used regression discontinuity to assess the effect of BCG vaccination on COVID-19-related outcomes. On such a large population, this method allows for a precision that would be hard to achieve using a randomized controlled trial.Results. The odds ratios (95% CI) for COVID-19 cases and COVID-19-related hospitalizations were 1.0005 (.8130-1.1881) and 1.2046 (.7532-1.6560), allowing us to reject fairly modest effects of universal BCG vaccination. We can reject with 95% confidence that universal BCG vaccination reduces the number of cases by 19% and the number of hospitalizations by 25%.Conclusions. While the effect of a recent vaccination must be evaluated, we provide strong evidence that receiving the BCG vaccine at birth does not have a protective effect against COVID-19 among middle-aged individuals.