COVID-19 vaccine-associated myocarditis

Table 1 Summary of coronavirus disease 2019 vaccine-associated myocarditis studies

Ref.	Study design	Sample size	Main findings	Analysis
Salah and Mehta[5], 2021	Systematic review of 6 case reports and 2 case series with a total of 15 patients	15 individuals who developed myocarditis following a COVID-19 vaccine, regardless of the type or dose of the vaccine	(1) 60% of the myocarditis related COVID-19 vaccine cases were associated with the Pfizer-BioNTech™ vaccine, 33% were associated with the Moderna™ vaccine, and 7% were associated with the Johnson & Johnson™ vaccine; (2) All the myocarditis related to the Moderna™ vaccine (5/5) occurred following the second dose of the vaccine, whereas 6/9 (66.7%) of the myocarditis related to the Pfizer-BioNTech™ vaccine occurred following the second dose of the vaccine; (3) Peak cardiac troponin I level (ng/mL) was reported in 13/15 patients, and it ranged between 0.37 and 51.37 ng/mL (mean 12.9 ng/mL). Peak troponin T levels were reported in the other 2/15 patients and were 854 ng/L and 1693 ng/L; (4) Transthoracic echocardiogram in all these patients showed preserved LVEF; exact LVEF value was reported in 13/15 patients with a mean LVEF of 53.5% and a range of 48% to 65%. In the other 2/15 patients, the LVEF was reported as normal with no value; (5) There were no regional wall abnormalities in 14/15 of the patients; 1 patient had subtle apical septal and apical lateral hypokinesis with a LVEF of 52%; and (6) All patients recovered within 6 d of their presentation with complications reported	(1) Myocarditis related to COVID-19 vaccines mostly occurs in young male individuals following the 2nd dose of the vaccine; (2) Myocarditis related to COVID-19 vaccines mostly occurs with mRNA vaccines (i.e., Pfizer-BioNTech™ and Moderna™ COVID-19 vaccines); (3) In all the reported cases of myocarditis related to COVID-19 vaccine, clinical symptoms resolved within 6 d with preservation of the cardiac function; and (4) No complications were reported in any of these patients showing that myocarditis related to COVID-19 vaccine has an overall fast recovery with no short-term complications
Mevorach et al[4], 2021	Retrospective review of myocarditis cases from the Israeli Ministry of Health database between December 2020 and May 2021	142 Israeli patients diagnosed with myocarditis within 21 d of receiving the first dose of Pfizer-BioNTech™ vaccine or 30 d of receiving the second dose	(1) In the 136 cases of definite or probable myocarditis with recent vaccination, the clinical presentation in 129 was generally mild, with resolution of myocarditis in most cases, as judged by clinical symptoms and inflammatory markers and troponin elevation, electrocardiographic and echocardiographic normalization, and a relatively short length of hospital stay; one fulminant case was fatal; (2) As compared with the expected incidence of myocarditis based on historical data, the standardized incidence ratio was 5.34 (95%CI: 4.48-6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 yr (13.60; 95%CI: 9.30-19.20); and (3) Definite or probable cases of myocarditis among persons between the ages of 16 and 19 yr within 21 d after the second vaccine dose occurred in approximately 1 of 6637 male recipients and in 1 of 99853 female recipients	(1) There was a slight increase in the incidence of myocarditis after the Pfizer-BioNTech™ vaccine, particularly after the second dose among young male recipients; and (2) The incidence of myocarditis after two doses of the Pfizer-BioNTech™ mRNA vaccine was low but higher than the incidence among unvaccinated persons and among historical controls, driven primarily by young males after receiving their second dose
Rosner et al[6], 2021	Case series of 7 patients hospitalized for acute myocarditis-like illness after COVID-19 vaccination from 2 United States medical centers	Seven males, all < 40 years old	(1) Six patients received an mRNA vaccine (Moderna™ or Pfizer-BioNTech™), and 1 received the adenovirus vaccine (Johnson and Johnson™); (2) All patients presented 3 to 7 d after vaccination with acute onset chest pain and troponin elevations; EKG varied from normal to 1 mm ST segment elevations; Echocardiograms showed left ventricular ejection fraction ranging from 35% to 62%, with 5 of 7 having some degree of hypokinesis; (3) Multifocal subepicardial late gadolinium enhancement was present in 7 of 7 patients and additional midmyocardial late gadolinium enhancement was found in 4 of 7 patients; and (4) Treatment included β-blocker and anti-inflammatory medication. Hospital length of stay was 3 ± 1 d, and all patients’ symptoms resolved by hospital discharge	(1) There is a potential causal association with vaccination given the temporal relationship, clinical presentation, and cardiac magnetic resonance imaging findings; (2) Vaccine-associated myocarditis appears to have a favorable clinical course; and (3) The benefits of vaccination outweigh the risks of vaccine-related myocarditis in younger adults given the potential morbidity of COVID-19 infection
Dionne et al[7], 2021	Case series of 15 adolescents at single United States center	15 adolescents ages 12-18 years old hospitalized with myocarditis after receiving Pfizer-BioNTech™ COVID-19 vaccine	(1) 14 children were male, and 1 child was female; (2) Symptoms started 1-6 d following vaccine administration (14 of 15 occurring after second dose); common symptoms included chest pain, fever, myalgia, and headache; (3) Elevated troponins found in all 15 cases; (4) Cardiac MRI findings were consistent with myocarditis in 13 patients, with 12 patients showing evidence of late gadolinium enhancement; (5) No patients required intensive care and the median length of hospital stay was 2 d (range 1-5 d); and (6) At 1-to-13-d follow-up after hospital discharge, 11 patients had full resolution, 1 patient had persistent borderline low LV systolic dysfunction (EF = 54%), 3 patients had mildly elevated troponins, 1 patient had nonsustained ventricular tachycardia on ambulatory monitor	(1) Following Pfizer-BioNTech™ vaccination, most cases of myocarditis were diagnosed in male children after the second dose; (2) All patients had a benign clinical course; and (3) Long-term risks of post-vaccine myocarditis in the child population remains unknown

COVID-19: Coronavirus disease 2019; MRI: Magnetic resonance imaging; EKG: Electrocardiogram; LVEF: Left ventricular ejection fraction.