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. 2024 Sep 6:76:102809.
doi: 10.1016/j.eclinm.2024.102809. eCollection 2024 Oct.

Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study

Supriya S Jain  1 , Steven A Anderson  2 , Jeremy M Steele  3 , Hunter C Wilson  4 , Juan Carlos Muniz  5 , Jonathan H Soslow  6 , Rebecca S Beroukhim  7 , Victoria Maksymiuk  1 , Xander Jacquemyn  8 , Olivia H Frosch  9 , Brian Fonseca  10 , Ashraf S Harahsheh  11 , Sujatha Buddhe  12 , Ravi C Ashwath  13 , Deepika Thacker  14 , Shiraz A Maskatia  15 , Nilanjana Misra  16 , Jennifer A Su  17 , Saira Siddiqui  18 , Danish Vaiyani  19 , Aswathy K Vaikom-House  20 , M Jay Campbell  21 , Jared Klein  22 , Sihong Huang  23 , Christopher Mathis  24 , Matthew D Cornicelli  25 , Madhu Sharma  26 , Lakshmi Nagaraju  27 , Jocelyn Y Ang  28 , Santosh C Uppu  29 , Preeti Ramachandran  30 , Jyoti K Patel  31 , Frank Han  32 , Jason G Mandell  33 , Jyothsna Akam-Venkata  34 , Michael P DiLorenzo  35 , Michael Brumund  36 , Puneet Bhatla  37 , Parham Eshtehardi  38 , Karina Mehta  39 , Katherine Glover  3 , Matthew L Dove  4 , Khalifah A Aldawsari  5 , Anupam Kumar  6 , Spencer B Barfuss  7 , Adam L Dorfman  9 , Prashant K Minocha  10 , Alexandra B Yonts  11 , Jenna Schauer  12 , Andrew L Cheng  17 , Joshua D Robinson  25 , Zachary Powell  20 , Shubhika Srivastava  14 , Anjali Chelliah  18 , Yamuna Sanil  28 , Lazaro E Hernandez  22 , Lasya Gaur  8 , Michael Antonchak  37 , Marla Johnston  36 , Jonathan D Reich  2 , Narayan Nair  2 , Elizabeth D Drugge  1 , Lars Grosse-Wortmann  39
Affiliations

Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study

Supriya S Jain et al. EClinicalMedicine. .

Erratum in

  • Corrigendum to "Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study".
    Jain SS, Anderson SA, Steele JM, Wilson HC, Muniz JC, Soslow JH, Beroukhim RS, Maksymiuk V, Jacquemyn X, Frosch OH, Fonseca B, Harahsheh AS, Buddhe S, Ashwath RC, Thacker D, Maskatia SA, Misra N, Su JA, Siddiqui S, Vaiyani D, Vaikom-House AK, Campbell MJ, Klein J, Huang S, Mathis C, Cornicelli MD, Sharma M, Nagaraju L, Ang JY, Uppu SC, Ramachandran P, Patel JK, Han F, Mandell JG, Akam-Venkata J, DiLorenzo MP, Brumund M, Bhatla P, Eshtehardi P, Mehta K, Glover K, Dove ML, Aldawsari KA, Kumar A, Barfuss SB, Dorfman AL, Minocha PK, Yonts AB, Schauer J, Cheng AL, Robinson JD, Powell Z, Srivastava S, Chelliah A, Sanil Y, Hernandez LE, Gaur L, Antonchak M, Johnston M, Reich JD, Nair N, Drugge ED, Grosse-Wortmann L. Jain SS, et al. EClinicalMedicine. 2025 May 21;84:103268. doi: 10.1016/j.eclinm.2025.103268. eCollection 2025 Jun. EClinicalMedicine. 2025. PMID: 40496878 Free PMC article.

Abstract

Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM).

Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging.

Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p < 0.001) and cardiac dysfunction was less common (17% vs. 68%, p < 0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p < 0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p = 0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up.

Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM.

Funding: The U.S. Food and Drug Administration.

Keywords: COVID-19 vaccine-associated myocarditis; Cardiac MRI; LGE late gadolinium enhancement; MIS-C multisystem inflammatory syndrome in children; Myocardial injury; Myocarditis.

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Conflict of interest statement

SSJ, LGW, SA, JMS, HCW, JCM, JHS, RSB, VM, XJ, OHF, BF, SB, RCA, SAM, NM, JAS, SS, DV, AKVH, MJC, JK, SH, CM, MDC, MS, LN, JYA, SCU, PR, JKP, JGM, JAV, MPD, MB, PB, PE, KM, KG, MLD, KAA, AK, SBB, ALD, PKM, JS, ALC, JDR, ZP, AC, YS, LG, MA, MJ, JDR, NN, EDD report no competing interests. ASH: Site PI for the CAMP study—NHLBI funded, Site PI for MUSIC—NIH funded, Site PI for PREVAIL, supported by a sub-agreement from the Johns Hopkins University with funds provided by Grant No. R61HD105591 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the Office of the Director, National Institute of Health (OD). Scientific advisory board member of OP2 DRUGS (“OP2”), states that no work has been done. ABY: Institution received funds for conducting phase 3 clinical trials for Pfizer mRNA COVID-19 vaccine (C4591007 and C4591048). LEH: Patent US11457889B2, issued: Oct 4, 2022, Patent US2023/0016283A1 Published: Jan 19, 2023. JK: $530 Honorarium for speaking at Cleveland Clinic Valve Disease, Structural Interventions, and Diastology/Imaging Summit in 2/2023. FH: Payment for Expert Testimony in pending court case as an expert witness to discuss the risk of C-VAM. DT and SS: Grant or contract from New England Research Institute for participation in Pediatric Heart Network CAMP Study. MJC: Subject matter expert for CDC CISA program, Consulting fees Longerone Inc.

Figures

Fig. 1
Fig. 1
Histogram of the age distribution within the cohort with COVID-19 vaccine-associated myocarditis.
Fig. 2
Fig. 2
Distribution pattern and frequency of myocardial late gadolinium enhancement (LGE) in COVID-19 vaccine-associated myocarditis (based on the American Heart Association left ventricular myocardial 17-segment model)at initial presentation (left) and at follow-up (right). The percentages indicate the frequency of LGE involvement in each of the myocardial segments, with darker colors corresponding to greater prevalence. LGE was common in the basal and mid inferolateral segments with an improvement demonstrated at follow-up.
Fig. 3
Fig. 3
Late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging of the left ventricle in two patients with COVID-19 vaccine-associated myocarditis (CVAM) at presentation and at one year follow-up. Patient 1 demonstrates marked multifocal LGE (A and B, yellow arrow heads) at presentation with notable improvement after one year (E and F, yellow arrows). Patient 2 shows LGE at presentation (C and D, yellow arrows) with persistence at one year (G and H, yellow arrows).
Fig. 4
Fig. 4
Risk factors for late gadolinium enhancement (LGE) in COVID-19 vaccine-associated myocarditis. The likelihood of LGE was highest in adolescent or young adult males and in those who presented after the first or second dose (vs. the third dose) of the mRNA vaccine.
Fig. 5
Fig. 5
Key illustration: Initial presentation, myocardial injury and outcomes, in young patients with COVID-19 vaccine associated myocarditis.
Fig. 6
Fig. 6
Presumed pathophysiology of cardiac involvement in COVID-19 vaccine-associated myocarditis (C-VAM) and multi-system inflammatory syndrome in children (MIS-C). In C-VAM, the mRNA vaccine induces an immunologic process that targets the myocardium, resulting in cardiomyocyte necrosis. In MIS-C, the body mounts an overwhelming inflammatory response to a preceding infection with SARS-CoV-2, affecting multiple organ systems, including the heart. This may result in transient cardiac dysfunction with a relatively mild myocardial injury.
See this image and copyright information in PMC

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