UK Health Security Agency, London, United Kingdom.
NIHR Health Protection Research Unit in Vaccines and Immunisation, London School of Hygiene and Tropical Medicine, London, United Kingdom.
PLoS Med. 2023 Jun 7;20(6):e1004245. doi: 10.1371/journal.pmed.1004245. eCollection 2023 Jun.
BACKGROUND: An increased risk of myocarditis or pericarditis after priming with mRNA Coronavirus Disease 2019 (COVID-19) vaccines has been shown but information on the risk post-booster is limited. With the now high prevalence of prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we assessed the effect of prior infection on the vaccine risk and the risk from COVID-19 reinfection. METHODS AND FINDINGS: We conducted a self-controlled case series analysis of hospital admissions for myocarditis or pericarditis in England between 22 February 2021 and 6 February 2022 in the 50 million individuals eligible to receive the adenovirus-vectored vaccine (ChAdOx1-S) for priming or an mRNA vaccine (BNT162b2 or mRNA-1273) for priming or boosting. Myocarditis and pericarditis admissions were extracted from the Secondary Uses Service (SUS) database in England and vaccination histories from the National Immunisation Management System (NIMS); prior infections were obtained from the UK Health Security Agency's Second-Generation Surveillance Systems. The relative incidence (RI) of admission within 0 to 6 and 7 to 14 days of vaccination compared with periods outside these risk windows stratified by age, dose, and prior SARS-CoV-2 infection for individuals aged 12 to 101 years was estimated. The RI within 27 days of an infection was assessed in the same model. There were 2,284 admissions for myocarditis and 1,651 for pericarditis in the study period. Elevated RIs were only observed in 16- to 39-year-olds 0 to 6 days postvaccination, mainly in males for myocarditis. Both mRNA vaccines showed elevated RIs after first, second, and third doses with the highest RIs after a second dose 5.34 (95% confidence interval (CI) [3.81, 7.48]; p < 0.001) for BNT162b2 and 56.48 (95% CI [33.95, 93.97]; p < 0.001) for mRNA-1273 compared with 4.38 (95% CI [2.59, 7.38]; p < 0.001) and 7.88 (95% CI [4.02, 15.44]; p < 0.001), respectively, after a third dose. For ChAdOx1-S, an elevated RI was only observed after a first dose, RI 5.23 (95% CI [2.48, 11.01]; p < 0.001). An elevated risk of admission for pericarditis was only observed 0 to 6 days after a second dose of mRNA-1273 vaccine in 16 to 39 year olds, RI 4.84 (95% CI [1.62, 14.01]; p = 0.004). RIs were lower in those with a prior SARS-CoV-2 infection than in those without, 2.47 (95% CI [1.32,4.63]; p = 0.005) versus 4.45 (95% [3.12, 6.34]; p = 0.001) after a second BNT162b2 dose, and 19.07 (95% CI [8.62, 42.19]; p < 0.001) versus 37.2 (95% CI [22.18, 62.38]; p < 0.001) for mRNA-1273 (myocarditis and pericarditis outcomes combined). RIs 1 to 27 days postinfection were elevated in all ages and were marginally lower for breakthrough infections, 2.33 (95% CI [1.96, 2.76]; p < 0.001) compared with 3.32 (95% CI [2.54, 4.33]; p < 0.001) in vaccine-naïve individuals respectively. CONCLUSIONS: We observed an increased risk of myocarditis within the first week after priming and booster doses of mRNA vaccines, predominantly in males under 40 years with the highest risks after a second dose. The risk difference between the second and the third doses was particularly marked for the mRNA-1273 vaccine that contains half the amount of mRNA when used for boosting than priming. The lower risk in those with prior SARS-CoV-2 infection, and lack of an enhanced effect post-booster, does not suggest a spike-directed immune mechanism. Research to understand the mechanism of vaccine-associated myocarditis and to document the risk with bivalent mRNA vaccines is warranted.
背景:mRNA 冠状病毒病 2019 (COVID-19) 疫苗接种后心肌炎或心包炎的风险增加已得到证实,但关于加强针后风险的信息有限。随着现在 SARS-CoV-2 感染的高流行率,我们评估了既往感染对疫苗风险和 COVID-19 再感染风险的影响。
方法和发现:我们在英格兰进行了一项基于病例的自我对照研究,纳入了 2021 年 2 月 22 日至 2022 年 2 月 6 日期间年龄在 12 至 101 岁之间、有资格接种腺病毒载体疫苗(ChAdOx1-S)进行初级免疫或 mRNA 疫苗(BNT162b2 或 mRNA-1273)进行初级或加强免疫的 5000 万人中的心肌炎或心包炎住院病例。心肌炎和心包炎的住院记录从英格兰的二级使用服务(SUS)数据库中提取,疫苗接种史从国家免疫管理系统(NIMS)中提取;既往感染则从英国卫生安全局的第二代监测系统中获取。对年龄、剂量和既往 SARS-CoV-2 感染分层的个体,在 0 至 6 天和 7 至 14 天接种疫苗期间与接种疫苗期间之外的时间段相比,评估疫苗接种后 0 至 6 天和 7 至 14 天内的入院相对发病率(RI)。在同一模型中评估了感染后 27 天内的 RI。研究期间共有 2284 例心肌炎和 1651 例心包炎住院。在 16 至 39 岁的人群中,仅在接种后 0 至 6 天观察到 RI 升高,主要是男性的心肌炎。mRNA 疫苗在第一、第二和第三剂后均显示出升高的 RI,第二剂后 RI 最高,BNT162b2 为 5.34(95%置信区间[3.81,7.48];p<0.001),mRNA-1273 为 56.48(95%置信区间[33.95,93.97];p<0.001),而第三剂后则分别为 4.38(95%置信区间[2.59,7.38];p<0.001)和 7.88(95%置信区间[4.02,15.44];p<0.001)。对于 ChAdOx1-S,仅在接种第一剂后观察到 RI 升高,RI 为 5.23(95%置信区间[2.48,11.01];p<0.001)。仅在 16 至 39 岁的人群中,mRNA-1273 疫苗接种后 6 天内观察到第二剂后心包炎的入院风险升高,RI 为 4.84(95%置信区间[1.62,14.01];p=0.004)。与未感染 SARS-CoV-2 的人相比,既往感染 SARS-CoV-2 的人的 RI 较低,接种第二剂 BNT162b2 后为 2.47(95%置信区间[1.32,4.63];p=0.005),而 mRNA-1273 则为 19.07(95%置信区间[8.62,42.19];p<0.001)(心肌炎和心包炎结局合并)。感染后 1 至 27 天的 RI 在所有年龄组中均升高,突破性感染的 RI 略低,分别为 2.33(95%置信区间[1.96,2.76];p<0.001)和 3.32(95%置信区间[2.54,4.33];p<0.001)。
结论:我们观察到 mRNA 疫苗初级和加强免疫后 1 周内心肌炎的风险增加,主要是 40 岁以下男性,第二剂后的风险最高。mRNA-1273 疫苗用于加强免疫时的 RI 明显低于初级免疫时,而其含有的 mRNA 量为初级免疫时的一半。既往感染 SARS-CoV-2 的人的风险较低,且加强针后无增强作用,这表明不是由 Spike 蛋白引起的免疫机制。需要研究以了解疫苗相关心肌炎的发病机制,并记录 bivalent mRNA 疫苗的风险。
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