Decoding the Human Genetic and Immunological Basis of COVID-19 mRNA Vaccine-Induced Myocarditis

Bolze, Alexandre; Mogensen, Trine H.; Zhang, Shen-Ying; Abel, Laurent; Andreakos, Evangelos; Arkin, Lisa M.; Borghesi, A.; Brodin, Petter; Hagin, David; Novelli, Giuseppe; Okada, Satoshi; Peter, Jonny; Rénia, Laurent; Sévère, Karine; Tiberghien, Pierre; Vinh, Donald C.; Aiuti, Alessandro; Al‐Muhsen, Saleh; Al‐Mulla, Fahd; Amara, Ali; Anderson, Mark S.; Arias, Andrés A.; Feldman, Hagit Baris; Bastard, Paul; Belot, Alexandre; Biggs, Catherine M.; Bogunovic, Dusan; Bousfiha, Ahmed Aziz; Butte, Manish J.; Christodoulou, John; Cobat, Aurélie; Colobran, Roger; Condino‐Neto, Antônio; Constantinescu, Stefan N.; Dalgard, Clifton L.; Duval, Xavier; Eloy, Philippine; Espinosa-Padilla, Sara; Fellay, Jacques; Flores, Carlos; Franco, José Luis; Froidure, Antoine; Gorochov, Guy; Gregersen, Peter K.; Haerynck, Filomeen; Halwani, Rabih; Hammarström, Lennart; Itan, Yuval; Jouanguy, Emmanuelle; Karamitros, Timokratis; Lau, Yu‐Lung; Mansouri, Davood; Mentré, France; Meyts, Isabelle; Mironska, Kristina; Morio, Tomohiro; Ng, Lisa F. P.; Novelli, Antonio; O’Farrelly, Cliona; Okamoto, Ken‐ichi; Özçelık, Tayfun; Pan‐Hammarström, Qiang; Diego, Rebeca Pérez de; Pérez‐Tur, Jordi; Perlin, David S.; Pesole, Graziano; Planas, Anna M.; Prando, Carolina; Pujol, Aurora; Resnick, Igor B.; Rodríguez‐Gallego, Carlos; Sancho‐Shimizu, Vanessa; Šedivá, Anna; Seppänen, Mikko R. J.; Shahrooei, Mohammed; Shcherbina, Anna; Slabý, Ondřej; Soler‐Palacín, Pere; Soumelis, Vassili; Spaan, András N.; Tancevski, Ivan; Tangye, Stuart G.; Tayoun, Ahmad Abou; Temel, Şehime Gülsün; Thorball, Christian W; Trouillet‐Assant, Sophie; Turvey, Stuart E.; Uddin, K. M. Furkan; Beek, Diederik van de; Bernuth, Horst von; Zhang, Qian; Cirulli, Elizabeth T.; Casanova, Jean‐Laurent; Hsieh, Elena W.Y.

doi:10.1007/s10875-022-01372-9

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…A possible mechanism could be the hypersensitivity reaction, the host genetics (e.g., the variants in the genes encoding HLA), immune cross-reactivity, and sex-related factors [6]. The hypotheses most often addressed were the hyperimmune or inflammatory response, autoimmunity triggered by molecular mimicry, delayed hypersensitivity, eosinophilic myocarditis, and hypersensitivity to the vehicle components of the vaccine [34][35][36][37]. As the mRNA vaccine platform is a new technology associated with most cases of myocarditis/pericarditis, we have yet to understand the role of the vaccine's properties in the mechanism of myocarditis.…”

Section: Discussionmentioning

confidence: 99%

Myocarditis and Pericarditis following COVID-19 Vaccination in Thailand

et al. 2023

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Background: Myocarditis and pericarditis cases following Coronavirus 2019 (COVID-19) vaccination were reported worldwide. In Thailand, COVID-19 vaccines were approved for emergency use. Adverse event following immunization (AEFI) surveillance has been strengthened to ensure the safety of the vaccines. This study aimed to describe the characteristics of myocarditis and pericarditis, and identify the factors associated with myocarditis and pericarditis following COVID-19 vaccination in Thailand. Method: We carried out a descriptive study of reports of myocarditis and pericarditis to Thailand’s National AEFI Program (AEFI-DDC) between 1 March and 31 December 2021. An unpaired case–control study was conducted to determine the factors associated with myocarditis and pericarditis after the CoronaVac, ChAdOx1-nCoV, BBIBP-CorV, BNT162b2, and mRNA-1273 vaccines. The cases consisted of COVID-19 vaccine recipients who met the definition of confirmed, probable, or suspected cases of myocarditis or pericarditis within 30 days of vaccination. The controls were people who underwent COVID-19 vaccination between 1 March and 31 December 2021, with no adverse reactions documented after vaccination. Results: Among the 31,125 events recorded in the AEFI-DDC after 104.63 million vaccinations, 204 cases of myocarditis and pericarditis were identified. The majority of them were male (69%). The median age was 15 years (interquartile range (IQR): 13–17). The incidence was highest following the BNT162b2 vaccination (0.97 cases per 100,000 doses administered). Ten deaths were reported in this study; no deaths were reported among children who received the mRNA vaccine. Compared with the age-specific incidence of myocarditis and pericarditis in Thailand before the introduction of the COVID-19 vaccination, the incidence of myocarditis and pericarditis after the BNT162b2 vaccine was greater in the 12–17 and 18–20 age groups in both males and females. It was higher after the second dose in 12- to 17-year-olds (2.68 cases per 100,000 doses administered) and highest after the second dose in male 12- to 17-year-olds (4.43 cases per 100,000 doses administered). Young age and a mRNA-based vaccination were associated with myocarditis and pericarditis following administration of the COVID-19 vaccine after multivariate analysis. Conclusions: Myocarditis and pericarditis following vaccination against COVID-19 were uncommon and mild, and were most likely to affect male adolescents. The COVID-19 vaccine offers the recipients enormous benefits. The balance between the risks and advantages of the vaccine and consistent monitoring of AEFI are essential for management of the disease and identification of AEFI.

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Section: Discussionmentioning

confidence: 99%

Myocarditis and Pericarditis following COVID-19 Vaccination in Thailand

et al. 2023

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“…For example, myocarditis and myopericarditis have been reported as considerable rare complications [ 88 , 89 ]. Several case studies have also hypothesized that genetic variants and an IL-18-dependent immune response could be involved in the severe adverse effects following COVID-19 mRNA vaccination [ [90] , [91] , [92] ]. Nevertheless, the current findings of the benefit-risk assessment of COVID-19 mRNA vaccines encourage the continuous development of mRNA vaccines against SARS-CoV-2 variants of concern and other viruses that may emerge in the future.…”

Section: Discussionmentioning

confidence: 99%

Race with virus evolution: The development and application of mRNA vaccines against SARS-CoV-2

Lee¹,

Lin²,

Wu³

et al. 2023

Biomedical Journal

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“…Interesting results are starting to emerge for MIS-C and already suggest a pathogenesis different from that of COVID-19 pneumonia (152)(153)(154). Future research should also encompass other COVID-19related clinical manifestations, such as long COVID (13) and COVID toes (12), as well as severe adverse effects of vaccination (155) and breakthrough infections (140).…”

Section: Discussionmentioning

confidence: 99%

Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants

Cobat

Zhang

Effort

et al. 2023

Annu. Rev. Biomed. Data Sci.

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SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1–5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15–20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 6 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Decoding the Human Genetic and Immunological Basis of COVID-19 mRNA Vaccine-Induced Myocarditis

Cited by 9 publications

References 25 publications

Myocarditis and Pericarditis following COVID-19 Vaccination in Thailand

Myocarditis and Pericarditis following COVID-19 Vaccination in Thailand

Race with virus evolution: The development and application of mRNA vaccines against SARS-CoV-2

Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants

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