COVID-19 vaccination and cardiac dysfunction

Table 1 Incidence and clinical manifestations of myocarditis after coronavirus disease 2019 mRNA vaccination

Ref.	Type of vaccine	Study population	Incidence	Cardiac assessment methods	Main findings and clinical outcomes
Witberg et al[11], Israel	Pfizer-BioNTech	54/2558421 (21-63 yr)	2.13/100000	Clinical presentation, ECG, ECHO, MRI, Troponin T	Myocarditis = 10.69/100000 in male ages 16-29 yr, 25.92% had LV dysfunction, 76% = mild, 22% = intermediate, 1 case had cardiogenic shock, 1 case died of unknown cause, 0.51/100000 after 1st dose and 2.15/100000 after 2nd dose
Mevorach et al[12], Israel	Pfizer-BioNTech	136/9289765 (≥ 16 yr)	1.46/100000	Clinical presentation, ECHO, MRI, Troponin T, Endomyocardial biopsy	Myocarditis = 15.07/100000 in male ages 16-19 yr, 0.35/100000 after 1st dose, 2.28/100000 after 2nd dose, 94.85% = mild, 4.41% = intermediate, 1 case was fatal, endo-interstitial edema with neutrophils and mononuclear-cells infiltrates with no giant cells
Montgomery et al[13], United States	Pfizer-BioNTech/Moderna	23/2810000 (20-51 yr)	0.82/100000	Clinical presentation, ECG, ECHO, MRI, Troponin T	Myocarditis = 1.88/100000 after 1st dose, 3.49/100000 after 2nd dose, and 4.36/100000 in male after 2nd dose
Perez et al[14], United States	Pfizer-BioNTech/Moderna/Johnson and Johnson	7/175472 (12-106 yr)	55.35/100000, Person-yr	Clinical presentation, ECG, ECHO, MRI, Troponin T	The overall incidence rate was 55.35 (22.25–114.00) per 100000 person-yr during the 2 wk after a dose of vaccine. The IRR for myocarditis following COVID-19 mRNA vaccination was increased for males at 6.69 (2.35–15.52), but it was not statistically significant for females at 1.41 (0.03–8.45)
Das et al[15], United States	Pfizer-BioNTech	25/7735071 (12-17 yr)	0.32/100000	Clinical presentation, ECG, ECHO, MRI, Troponin T, CRP	Myocarditis = 0.04/100000 after 1st dose, 0.28/100000 after 2nd dose, and 0.26/100000 in male after 2nd dose
Li et al[16], United States	Pfizer-BioNTech/Moderna/Janssen	Age ≥ 12 yr	0.598/100000	VAERS	Pfizer–BioNTech had a higher incidence rate of 0.670/100000 than the rate of 0.498/100000 found for Moderna. The incidence rate following the 2nd dose was twice that of the 1st dose and was the highest in adolescents aged 12-17 yr, at 2.094/100000. The Janssen vaccine was not associated with myocarditis or pericarditis
Patone et al[17], United Kingdom	Pfizer-BioNTech/Moderna/AstraZeneca	1615/38615491 (Age ≥ 16 yr)	4.18/100000	NIMS	The IRR of myocarditis = 1.76, 1.45, 8.38 after 1st dose of AstraZeneca, Pfizer-BioNTech, Moderna. IRR of myocarditis = 1.75, 23.10 after 2nd dose of Pfizer-BioNTech, Moderna. There was an increase in the risk of myocarditis within 1 wk after 1st dose of adenovirus and mRNA vaccines and a higher increased risk after 2nd dose of both mRNA vaccines, especially in under 40 yr
Simone et al[18], United States	Pfizer-BioNTech/Moderna	15/2392924 (Age ≥ 18 yr)	0.63/100000	KPSC members with clinical presentation, ECG, ECHO, Troponin I	Myocarditis = 0.08/100000 after 1st dose, 0.58/100000 after 2nd dose over a 10-d period, all were men aged 20-32 yr. The IRR of myocarditis = 0.38 after 1st dose and 2.7 after 2nd dose
Nygaard et al[19], Denmark	Pfizer-BioNTech	15/261334 (12-17 yr)	5.74/100000	Clinical presentation, ECG, ECHO, MRI, Troponin	Myocarditis = 3.06/100000 after 1st dose, 2.68/100000 after 2nd dose mostly in male (M:F = 6:1)
Husby et al[20], Denmark	Pfizer-BioNTech/Moderna	269/4931775 (Age ≥ 12 yr)	5.45/100000	Danish Vaccination Register	HR of myocarditis/pericarditis = 1.34, 3.92 within 28 d from the vaccination of Pfizer-BioNTech, Moderna respectively. Myocarditis or pericarditis occurred at 1.4/100000 for Pfizer-BioNTech and 4.2/100000 for Moderna. Vaccination with Moderna vaccine was associated with an increased risk of myocarditis or pericarditis, especially in aged 12-39 yr
Diaz et al[21], United States	Pfizer-BioNTech/Moderna/Janssen	57/2000287 (26-70 yr)	2.85/100000	Clinical presentation, ECG, ECHO, Troponin	Myocarditis = 1.0/100000 and pericarditis = 1.8/100000. Myocarditis and pericarditis were observed after the COVID-19 vaccination. Myocarditis developed rapidly in younger patients, mostly after the 2nd dose. Pericarditis affected older patients later, after either the 1st or 2nd dose
Chouchana et al[22], WHO	Pfizer-BioNTech/Moderna	2277/716576 reports	NA	VigiBase	Over all myocarditis = 3.57/100000 with 12–17 yr = 3.69/100000, 18–29 yr = 1.97/100000, and ≥ 30 yr = 0.21/100000. Younger male aged 12–17 yr were more prone to report myocarditis or pericarditis with 22.3/100000. The median time to onset for myocarditis was 3 d after vaccine injection
Barda et al[23], Israel	Pfizer-BioNTech	21/938812	2.23/100000	Clinical presentation, ECG, ECHO, Troponin	Vaccination was most strongly associated with an elevated risk of myocarditis [risk ratio, 3.24 (1.55-12.44)]. Alternatively, SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis [risk ratio, 18.28 (3.95-25.12)]. The BNT162b2-mRNA vaccine increased the incidence of a few adverse events over a 42-d follow-up period

ECG: Electrocardiography; ECHO: Echocardiography; HR: Hazard ratio; IRR: Incidence rate ratio; KPSC: Kaiser Permanente Southern California; M:F: Male to female; MRI: Magnetic resonance imaging; NA: Not available; NIMS: The English National Immunisation; ROR: Reporting odds ratio; VAERS: Vaccine Adverse Events Reporting System; VigiBase: World Health Organization (WHO) global safety database; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.