Background

Preapproval trials showed that messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.

Methods

We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan–Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2–infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.

Results

In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.

Conclusions

In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)

中文翻译：

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BNT162b2 mRNA Covid-19 疫苗在全国范围内的安全性

背景

预批准试验表明，基于信使 RNA (mRNA) 的针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的疫苗具有良好的安全性，但这些试验受到规模和患者组合的限制。需要评估 BNT162b2 mRNA 疫苗针对广泛潜在不良事件的安全性。

方法

我们使用以色列最大的医疗保健组织的数据来评估 BNT162b2 mRNA 疫苗的安全性。对于每一个潜在的不良事件，在以前没有诊断过该事件的人群中，我们根据社会人口统计学和临床​​变量将接种疫苗的人和未接种疫苗的人单独匹配。疫苗接种后 42 天的风险比和风险差异是使用 Kaplan-Meier 估计器得出的。为了将这些结果放在背景中，我们对 SARS-CoV-2 感染者与未感染者进行了类似的分析。在疫苗接种和 SARS-CoV-2 感染分析中也研究了相同的不良事件。

结果

在疫苗接种分析中，接种组和对照组平均各有 884,828 人。疫苗接种与心肌炎风险升高密切相关（风险比，3.24；95% 置信区间 [CI]，1.55 至 12.44；风险差异，每 100,000 人 2.7 起事件；95% CI，1.0 至 4.6）、淋巴结肿大（风险比率，2.43；95% CI，2.05 至 2.78；风险差异，每 10 万人中有 78.4 个事件；95% CI，64.1 至 89.3），阑尾炎（风险比率，1.40；95% CI，1.02 至 2.01；风险差异，5.0 个事件）每 10 万人中发生的事件；95% CI，0.3 至 9.9），以及带状疱疹感染（风险比，1.43；95% CI，1.20 至 1.73；风险差异，每 10 万人中 15.8 次事件；95% CI，8.2 至 24.2）。SARS-CoV-2 感染与心肌炎风险显着增加相关（风险比，18.28；95% CI，3.95 至 25.12；风险差异，每 10 万人中有 11.0 起事件；95% CI，5.6 至 15.8）以及其他严重的心肌炎风险不良事件，包括心包炎、心律失常、深静脉血栓、肺栓塞、心肌梗死、颅内出血和血小板减少症。

结论

在这项全国范围内大规模疫苗接种的研究中，BNT162b2 疫苗与所检查的大多数不良事件的风险升高无关。该疫苗与心肌炎的过高风险相关（每 100,000 人中有 1 至 5 起事件）。感染 SARS-CoV-2 后，这种潜在严重不良事件和许多其他严重不良事件的风险大幅增加。（由哈佛医学院和 Clalit 研究所的 Ivan 和 Francesca Berkowitz 家庭生活实验室合作资助。）