Incidence, risk factors, natural history, and hypothesised mechanisms of myocarditis and pericarditis following covid-19 vaccination: living evidence syntheses and review.
Incidence, risk factors, natural history, and hypothesised mechanisms of myocarditis and pericarditis following covid-19 vaccination: living evidence syntheses and review.
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DOI：
10.1136/bmj-2021-069445
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发表时间：
2022-07-13
影响因子：
105.7
通讯作者：
Hartling, Lisa
中科院分区：
文献类型：
--
作者：
Pillay, Jennifer;Gaudet, Lindsay;Wingert, Aireen;Bialy, Liza;Mackie, Andrew S.;Paterson, D. Ian;Hartling, Lisa
综合关于使用针对COVID-19的mRNA疫苗后心肌炎和心包炎的发病率和风险因素、临床表现、病例的短期和长期结局以及拟议机制的证据。活体证据综合与审查。检索了Medline、Embase和科克伦图书馆，检索时间为2020年10月6日至2022年1月10日;参考文献列表和灰色文献（至2021年1月13日）。一位评审员完成了筛选，另一位评审员使用机器学习程序对记录进行优先级排序，验证了50%的排除。第二位评审员使用修改后的乔安娜·布里格斯研究所工具，在全文、提取数据和（对于发生率和风险因素）偏差风险评估中验证了所有排除。使用GRADE（推荐、评估、开发和评价分级），团队共识确定了发生率和风险因素的证据评级的确定性。大型（> 10 000名参与者）或基于人群或多中心的观察性研究和监测数据（发病率和风险因素），报告在COVID-19 mRNA疫苗接种后确诊的心肌炎或心包炎;病例系列（n ≥ 5，介绍，短期临床病程和长期结局）;意见，信件，评论和主要研究集中在描述或支持假设的机制。纳入了46项研究（14项关于发病率，7项关于风险因素，11项关于特征和短期病程，3项关于长期结局，21项关于机制）。mRNA疫苗接种后心肌炎的发病率在男性青少年和男性年轻人中最高（年龄12 - 17岁，范围为每百万人50 - 139例（低确定性）; 18 - 29岁，每百万人28 - 147例（中等确定性））。对于5 - 11岁的女孩和男孩以及18 - 29岁的女性，接种BNT162b2（Pfizer/BioNTech）疫苗后心肌炎的发病率可能低于20例/百万（低确定性）。第三剂mRNA疫苗后的发病率具有非常低的确定性证据。对于18 - 29岁的个体，接种mRNA-1273（Moderna）后心肌炎的发病率可能高于辉瑞（中等确定性）。在12 - 17岁、18 - 29岁或18 - 39岁的个体中，与第一剂疫苗接种后≤ 30天相比，第二剂疫苗接种后≥ 31天的心肌炎或心包炎发生率可能较低（低确定性）。针对18 - 29岁男性的数据表明，给药间隔可能需要增加至≥ 56天，以大幅降低心肌炎或心包炎的发生率。对于临床病程和短期结局，仅发现一个5 - 11岁儿童的小型病例系列（n = 8）。在青少年和成人中，大多数（> 90%）心肌炎病例涉及中位年龄为20 - 30岁的男性，第二次给药后2 - 4天出现症状（71 - 100%）。大多数患者（≥ 84%）住院时间较短（2 - 4天）。对于心包炎，数据有限，但在患者年龄、性别、发病时间和住院率方面报告的变异性大于心肌炎。3个长期（3个月; n = 38）随访的病例系列提示持续的超声心动图异常，以及持续的症状或需要药物治疗或> 50%的患者活动受限。描述了16种假设的机制，几乎没有直接支持或反驳的证据。这些发现表明，青少年和年轻成年男性在mRNA疫苗接种后患心肌炎的风险最高。使用辉瑞疫苗而不是Moderna疫苗，并且在剂量之间等待超过30天可能是这一人群的首选。5 - 11岁儿童心肌炎的发病率非常罕见，但确定性很低。临床风险因素的数据非常有限。mRNA相关性心肌炎的临床过程似乎是良性的，尽管长期随访数据有限。采用适当检测（例如活检和组织形态学）的前瞻性研究将增强对机制的理解。
To synthesise evidence on incidence rates and risk factors for myocarditis and pericarditis after use of mRNA vaccination against covid-19, clinical presentation, short term and longer term outcomes of cases, and proposed mechanisms. Living evidence syntheses and review. Medline, Embase, and the Cochrane Library were searched from 6 October 2020 to 10 January 2022; reference lists and grey literature (to 13 January 2021). One reviewer completed screening and another verified 50% of exclusions, using a machine learning program to prioritise records. A second reviewer verified all exclusions at full text, extracted data, and (for incidence and risk factors) risk of bias assessments using modified Joanna Briggs Institute tools. Team consensus determined certainty of evidence ratings for incidence and risk factors using GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Large (>10 000 participants) or population based or multisite observational studies and surveillance data (incidence and risk factors) reporting on confirmed myocarditis or pericarditis after covid-19 mRNA vaccination; case series (n≥5, presentation, short term clinical course and longer term outcomes); opinions, letters, reviews, and primary studies focused on describing or supporting hypothesised mechanisms. 46 studies were included (14 on incidence, seven on risk factors, 11 on characteristics and short term course, three on longer term outcomes, and 21 on mechanisms). Incidence of myocarditis after mRNA vaccines was highest in male adolescents and male young adults (age 12-17 years, range 50-139 cases per million (low certainty); 18-29 years, 28-147 per million (moderate certainty)). For girls and boys aged 5-11 years and women aged 18-29 years, incidence of myocarditis after vaccination with BNT162b2 (Pfizer/BioNTech) could be fewer than 20 cases per million (low certainty). Incidence after a third dose of an mRNA vaccine had very low certainty evidence. For individuals of 18-29 years, incidence of myocarditis is probably higher after vaccination with mRNA-1273 (Moderna) compared with Pfizer (moderate certainty). Among individuals aged 12-17, 18-29, or 18-39 years, incidence of myocarditis or pericarditis after dose two of an mRNA vaccine for covid-19 might be lower when administered ≥31 days compared with ≤30 days after dose one (low certainty). Data specific to men aged 18-29 years indicated that the dosing interval might need to increase to ≥56 days to substantially drop myocarditis or pericarditis incidence. For clinical course and short term outcomes, only one small case series (n=8) was found for 5-11 year olds. In adolescents and adults, most (>90%) myocarditis cases involved men of a median 20-30 years of age and with symptom onset two to four days after a second dose (71-100%). Most people were admitted to hospital (≥84%) for a short duration (two to four days). For pericarditis, data were limited but more variation than myocarditis has been reported in patient age, sex, onset timing, and rate of admission to hospital. Three case series with longer term (3 months; n=38) follow-up suggested persistent echocardiogram abnormalities, as well as ongoing symptoms or a need for drug treatments or restriction from activities in >50% of patients. Sixteen hypothesised mechanisms were described, with little direct supporting or refuting evidence. These findings indicate that adolescent and young adult men are at the highest risk of myocarditis after mRNA vaccination. Use of a Pfizer vaccine over a Moderna vaccine and waiting for more than 30 days between doses might be preferred for this population. Incidence of myocarditis in children aged 5-11 years is very rare but certainty was low. Data for clinical risk factors were very limited. A clinical course of mRNA related myocarditis appeared to be benign, although longer term follow-up data were limited. Prospective studies with appropriate testing (eg, biopsy and tissue morphology) will enhance understanding of mechanism.
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