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文献精选 > 近年高分"mRNA疫苗"研究（IF≥30，近5年）

Myocarditis With COVID-19 mRNA Vaccines. ​

文献信息 ​

DOI10.1161/CIRCULATIONAHA.121.056135
PMID34281357
期刊Circulation
影响因子38.6
JCR 分区Q1
发表年份2021
被引次数507
关键词COVID-19, COVID-19疫苗, SARS-CoV-2, mRNA疫苗, 心肌炎
文献类型Journal Article, Review
ISSN0009-7322
页码471-484
期号144(6)
作者Biykem Bozkurt, Ishan Kamat, Peter J Hotez

一句话小结 ​

心肌炎作为2019冠状病毒病（COVID-19）mRNA疫苗的一种罕见并发症，特别在年轻男性和青少年中更为常见，接种第二剂疫苗后发生率约为每百万剂12.6例，患者通常在接种后2至3天内出现胸痛和心脏肌钙蛋白升高。尽管心肌炎的发病机制尚不明确，但研究表明，疫苗接种的益处仍大于风险，建议12岁及以上人群接种COVID-19疫苗。

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COVID-19 · COVID-19疫苗 · SARS-CoV-2 · mRNA疫苗 · 心肌炎

摘要 ​

心肌炎已被认定为2019冠状病毒病（COVID-19）mRNA疫苗的一种罕见并发症，尤其在年轻男性和青少年中更为常见。根据美国疾病控制与预防中心的数据，12至39岁人群中，第二剂mRNA疫苗接种后心肌炎/心包炎的发生率约为每百万剂12.6例。在已报告的病例中，心肌炎患者通常在接种第二剂mRNA疫苗后2至3天出现胸痛，并伴有心脏肌钙蛋白水平升高。心电图在大多数病例中显示异常，伴有ST段抬高，所有接受心脏磁共振成像检查的患者均显示心肌炎的迹象。没有急性COVID-19或其他病毒感染的证据。在一例中，心肌病基因检测结果为阴性，但针对某些自身抗原的自身抗体水平和自然杀伤细胞的频率均有所增加。尽管心肌炎的发病机制尚不明确，但已提出了几种可能的机制，包括严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）刺突蛋白与自身抗原之间的分子模拟、某些个体先前免疫途径的失调、对mRNA的免疫反应、免疫途径的激活及细胞因子表达的失调。心肌炎病例中男性占主导的原因尚不清楚，但可能与性激素在免疫反应和心肌炎中的差异以及女性心脏疾病的漏诊有关。几乎所有患者在接受治疗与否的情况下，均症状和体征得以缓解，诊断标志物和影像学检查结果也有所改善。尽管心肌炎病例较为罕见，但对COVID-19疫苗接种的利益-风险评估显示，各年龄段和性别组的平衡均为有利；因此，建议12岁及以上的所有人群接种COVID-19疫苗。

英文摘要 ​

Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels. ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients. There was no evidence of acute COVID-19 or other viral infections. In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased. Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed. The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women. Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment. Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.

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主要研究问题 ​

  1. 除了年轻男性，是否有其他人群在接种COVID-19 mRNA疫苗后发生心肌炎的风险增加？
  2. 在心肌炎病例中，患者的免疫反应与心肌损伤之间的关系是什么？
  3. 针对心肌炎的发生，是否有针对性的预防措施或监测建议可以应用于接种疫苗的人群？
  4. 目前有哪些研究正在探索心肌炎与COVID-19 mRNA疫苗之间的潜在机制？
  5. 心肌炎的症状和表现是否在不同年龄段或性别中有所不同，影响其诊断和治疗的方式？

核心洞察 ​

研究背景和目的 ​

随着新冠疫情的持续，COVID-19 mRNA疫苗的安全性引起了广泛关注。心肌炎作为一种罕见的疫苗并发症，尤其在年轻男性中更为突出。研究的目的是评估COVID-19 mRNA疫苗接种后心肌炎的发生率、临床表现及潜在机制，以提供更全面的安全性评估。

主要方法/材料/实验设计 ​

本研究通过对接种COVID-19 mRNA疫苗后出现心肌炎的病例进行回顾性分析，主要方法包括：

  • 收集病例数据，包括患者的年龄、性别、接种疫苗的时间、症状表现及实验室检查结果。
  • 进行心电图（ECG）和心脏磁共振成像（MRI）检查，以确认心肌炎的诊断。
  • 检测心脏标志物（如心肌肌钙蛋白）及自身抗体水平。
  • 分析心肌炎发生的潜在机制，包括分子模拟、免疫反应等。

以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  • 在12至39岁人群中，mRNA疫苗的心肌炎发生率约为每百万剂次12.6例。
  • 患者普遍在接种第二剂疫苗后2至3天内出现胸痛，伴随心肌肌钙蛋白水平升高。
  • 心电图大多数病例表现为ST段抬高，心脏MRI检查均显示心肌炎特征。
  • 无急性COVID-19或其他病毒感染的证据。
  • 某些病例中，自身抗体水平升高，且自然杀伤细胞频率增加。

主要结论/意义/创新性 ​

尽管心肌炎是COVID-19 mRNA疫苗的罕见并发症，但绝大多数患者在治疗或不治疗的情况下症状和体征均有好转。综合风险评估表明，COVID-19疫苗接种的益处超过潜在风险，建议所有12岁及以上人群接种疫苗。研究为疫苗安全性提供了重要数据支持，强调了继续推广疫苗接种的重要性。

研究局限性和未来方向 ​

  • 研究主要依赖病例报告，样本量相对较小，可能存在选择偏倚。
  • 对心肌炎机制的理解仍不完全，需进一步研究不同性别对免疫反应的影响。
  • 未来应开展大规模、长期的前瞻性研究，以监测疫苗接种后心肌炎的发生及其长期后果。
研究方面结果未来方向
心肌炎发生率每百万剂次12.6例大规模前瞻性研究
临床表现胸痛、心肌肌钙蛋白升高深入研究性别差异对免疫反应的影响
治疗效果大多数患者症状改善监测长期后果
风险评估疫苗益处超过风险持续评估疫苗安全性

参考文献 ​

  1. In-Depth Evaluation of a Case of Presumed Myocarditis After the Second Dose of COVID-19 mRNA Vaccine. - Alagarraju Muthukumar;Madhusudhanan Narasimhan;Quan-Zhen Li;Lenin Mahimainathan;Imran Hitto;Franklin Fuda;Kiran Batra;Xuan Jiang;Chengsong Zhu;John Schoggins;James B Cutrell;Carol L Croft;Amit Khera;Mark H Drazner;Justin L Grodin;Benjamin M Greenberg;Pradeep P A Mammen;Sean J Morrison;James A de Lemos - Circulation (2021)
  2. Pathogenesis of macrophage activation syndrome and potential for cytokine- directed therapies. - Grant S Schulert;Alexei A Grom - Annual review of medicine (2015)
  3. Consistent production of a higher TH1:TH2 cytokine ratio by stimulated T cells in men compared with women. - J A Girón-González;F J Moral;J Elvira;D García-Gil;F Guerrero;I Gavilán;L Escobar - European journal of endocrinology (2000)
  4. COVID-19 myocarditis: quantitative analysis of the inflammatory infiltrate and a proposed mechanism. - Sharon E Fox;Lacey Falgout;Richard S Vander Heide - Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology (2021)
  5. Myocarditis. A histopathologic definition and classification. - H T Aretz;M E Billingham;W D Edwards;S M Factor;J T Fallon;J J Fenoglio;E G Olsen;F J Schoen - The American journal of cardiovascular pathology (1987)
  6. Long COVID-19 or Post-Acute Sequelae of SARS-CoV-2 Infection in Children, Adolescents, and Young Adults. - Joseph R Hageman - Pediatric annals (2021)
  7. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. - Katalin Karikó;Michael Buckstein;Houping Ni;Drew Weissman - Immunity (2005)
  8. Prospects for a safe COVID-19 vaccine. - Barton F Haynes;Lawrence Corey;Prabhavathi Fernandes;Peter B Gilbert;Peter J Hotez;Srinivas Rao;Michael R Santos;Hanneke Schuitemaker;Michael Watson;Ann Arvin - Science translational medicine (2020)
  9. Multiorgan and Renal Tropism of SARS-CoV-2. - Victor G Puelles;Marc Lütgehetmann;Maja T Lindenmeyer;Jan P Sperhake;Milagros N Wong;Lena Allweiss;Silvia Chilla;Axel Heinemann;Nicola Wanner;Shuya Liu;Fabian Braun;Shun Lu;Susanne Pfefferle;Ann S Schröder;Carolin Edler;Oliver Gross;Markus Glatzel;Dominic Wichmann;Thorsten Wiech;Stefan Kluge;Klaus Pueschel;Martin Aepfelbacher;Tobias B Huber - The New England journal of medicine (2020)
  10. Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination. - Han W Kim;Elizabeth R Jenista;David C Wendell;Clerio F Azevedo;Michael J Campbell;Stephen N Darty;Michele A Parker;Raymond J Kim - JAMA cardiology (2021)

引用本文的文献 ​

  1. Coronavirus Disease-2019 and Heart Failure: A Scientific Statement From the Heart Failure Society of America. - Ankeet S Bhatt;Eric D Adler;Nancy M Albert;Anelechi Anyanwu;Nahid Bhadelia;Leslie T Cooper;Ashish Correa;Ersilia M Defilippis;Emer Joyce;Andrew J Sauer;Scott D Solomon;Orly Vardeny;Clyde Yancy;Anuradha Lala - Journal of cardiac failure (2022)
  2. The bitter news about sweet solutions for the post neonatal age. - Ran D Goldman - CJEM (2021)
  3. Narrative review on clinical considerations for patients with diabetes and COVID-19: More questions than answers. - Niki Katsiki;Ricardo Gómez-Huelgas;Dimitri P Mikhailidis;Pablo Pérez-Martínez - International journal of clinical practice (2021)
  4. Exploring the possible link between myocarditis and mRNA COVID-19 vaccines. - Gianfranco Sinagra;Marco Merlo;Aldostefano Porcari - European journal of internal medicine (2021)
  5. [Acute and chronic cardiac involvement in COVID-19]. - Dietrich Beitzke - Der Radiologe (2021)
  6. Severe COVID-19 vaccine associated myocarditis: Zebra or unicorn? - Nicholas S Hendren;Spencer Carter;Justin L Grodin - International journal of cardiology (2021)
  7. COVID-19 vaccination in patients with heart failure: a position paper of the Heart Failure Association of the European Society of Cardiology. - Giuseppe Rosano;Ewa A Jankowska;Robin Ray;Marco Metra;Magdy Abdelhamid;Stamatis Adamopoulos;Stefan D Anker;Antoni Bayes-Genis;Yury Belenkov;Tuvia B Gal;Michael Böhm;Ovidiu Chioncel;Alain Cohen-Solal;Dimitrios Farmakis;Gerasimos Filippatos;Arantxa González;Finn Gustafsson;Loreena Hill;Tiny Jaarsma;Fadi Jouhra;Mitja Lainscak;Ekaterini Lambrinou;Yury Lopatin;Lars H Lund;Davor Milicic;Brenda Moura;Wilfried Mullens;Massimo F Piepoli;Piotr Ponikowski;Amina Rakisheva;Arsen Ristic;Gianluigi Savarese;Petar Seferovic;Michele Senni;Thomas Thum;Carlo G Tocchetti;Sophie Van Linthout;Maurizio Volterrani;Andrew J S Coats - European journal of heart failure (2021)
  8. Providing children with COVID-19 vaccinations is challenging due to lack of data and wide-ranging parental acceptance. - Jiatong She;Lanqin Liu;Wenjun Liu - Acta paediatrica (Oslo, Norway : 1992) (2022)
  9. Familial hypercholesterolemia and COVID-19: A menacing but treatable vasculopathic condition. - Alpo Vuorio;Timo E Strandberg;Frederik Raal;Raul D Santos;Petri T Kovanen - Atherosclerosis plus (2021)
  10. Cardiac involvement in the long-term implications of COVID-19. - Benjamin A Satterfield;Deepak L Bhatt;Bernard J Gersh - Nature reviews. Cardiology (2022)

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