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.

中文翻译：

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对于既往感染过或未感染过 SARS-CoV-2 的人，在接受 COVID-19 mRNA 疫苗加强接种后以及在接受 COVID-19 治疗后出现心肌炎和心包炎的风险：英格兰的一项自我对照病例系列分析。

背景 研究表明，接种 2019 年冠状病毒病 (COVID-19) mRNA 疫苗后，心肌炎或心包炎的风险会增加，但有关加强后风险的信息有限。由于目前严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染的患病率很高，我们评估了既往感染对疫苗风险和 COVID-19 再次感染风险的影响。方法和结果 我们对 2021 年 2 月 22 日至 2022 年 2 月 6 日期间英格兰因心肌炎或心包炎入院的 5000 万名有资格接受腺病毒载体疫苗 (ChAdOx1-S) 的个体进行了自我对照病例系列分析，以进行初免或免疫接种。用于初免或加强的 mRNA 疫苗（BNT162b2 或 mRNA-1273）。心肌炎和心包炎入院情况是从英格兰的二次使用服务（SUS）数据库中提取的，疫苗接种史是从国家免疫管理系统（NIMS）中提取的；先前的感染是从英国卫生安全局的第二代监控系统获得的。对 12 至 101 岁个体按年龄、剂量和既往 SARS-CoV-2 感染情况进行分层，估计了接种疫苗后 0 至 6 天内和 7 至 14 天内入院的相对发生率 (RI) 与这些风险窗口之外的时期相比。在同一模型中评估感染后 27 天内的 RI。研究期间，有 2,284 例因心肌炎入院，1,651 例因心包炎入院。仅在接种后 0 至 6 天的 16 至 39 岁人群中观察到 RI 升高，主要是男性因心肌炎。两种 mRNA 疫苗在第一剂、第二剂和第三剂后均显示 RI 升高，其中 BNT162b2 的 RI 为 5.34（95% 置信区间 (CI) [3.81, 7.48]；p < 0.001），第二剂后 RI 最高为 56.48（95% CI [ mRNA-1273 的结果分别为 4.38 (95% CI [2.59, 7.38]; p < 0.001) 和 7.88 (95% CI [4.02, 15.44]; p < 0.001)。第三剂。对于 ChAdOx1-S，仅在第一次给药后观察到 RI 升高，RI 5.23（95% CI [2.48, 11.01]；p < 0.001）。在 16 至 39 岁的人群中，仅在注射第二剂 mRNA-1273 疫苗后 0 至 6 天，才观察到因心包炎入院的风险升高，RI 4.84（95% CI [1.62, 14.01]；p = 0.004）。既往感染过 SARS-CoV-2 的患者的 RI 低于未感染过的患者，分别为 2.47（95% CI [1.32,4.63]；p = 0.005）和 4.45（95% [3.12, 6.34]；p = 0）。001）在第二次 BNT162b2 剂量后，mRNA-1273 为 19.07（95% CI [8.62, 42.19]；p < 0.001）与 37.2（95% CI [22.18, 62.38]；p < 0.001）（心肌炎和心包炎结果相结合） ）。感染后 1 至 27 天，所有年龄段的 RI 均升高，突破性感染的 RI 略低，为 2.33（95% CI [1.96, 2.76]；p < 0.001），而 RI 为 3.32（95% CI [2.54, 4.33]；p < 0.001） ）分别在未接种疫苗的个体中。结论 我们观察到，在 mRNA 疫苗初免剂量和加强剂量后的第一周内，心肌炎的风险增加，主要是 40 岁以下的男性，第二剂接种后风险最高。对于 mRNA-1273 疫苗，第二剂和第三剂之间的风险差异尤其明显，该疫苗用于加强时的 mRNA 量是初免时的一半。既往感染过 SARS-CoV-2 的患者风险较低，且加强后缺乏增强效果，并不表明存在尖峰定向免疫机制。有必要进行研究以了解疫苗相关性心肌炎的机制并记录二价 mRNA 疫苗的风险。