Historically, smallpox and anthrax vaccines have been associated with acute myocarditis.
1
Among 790 cases reported in the WHO pharmacovigilance database between 1967 and 2020,
1
vaccine-associated myocarditis primarily affected young male adults (median age 24
years; 84% male individuals). Recently, the mRNA COVID-19 vaccines have also been
associated with myocarditis. In the USA, 1626 cases of mRNA COVID-19 vaccine-related
myocarditis were reported between December, 2020, and August, 2021, through the Vaccine
Adverse Event Reporting System (VAERS).
2
Similar to the previous cases of vaccine-associated myocarditis, the median age of
individuals with mRNA COVID-19 vaccine-associated myocarditis was 21 years, and 82%
were male.
2
The greater number of individuals with vaccine-related myocarditis in recent reports,
compared with previous figures of vaccine-related myocarditis in the WHO pharmacovigilance
database between 1967 and 2020, might relate to the high number of adolescent and
young adults vaccinated with mRNA COVID-19 vaccines.
3
Unlike previous myocarditis case series, intermediate-term outcomes and time course
of recovery after mRNA COVID-19 vaccine-associated myocarditis have not yet been reported.
In the USA, incidence of mRNA vaccine-related myocarditis within 21 days of the second
dose peaks in males aged 12–29 years (8·4 to 26·7 cases per 100 000 males).
4
Myocarditis risk is higher after SARS-CoV-2 virus infection than after mRNA COVID-19
vaccination.
4
In fact, myocarditis was diagnosed in 59·0 to 63·7 per 100 000 males aged 12–29 years
within 21 days of a positive SARS-CoV-2 molecular or antigen test.
4
The pattern of myocarditis after SARS-CoV-2 infection is similar to previously reported
patterns after viral infection, with adolescent and young adult males more commonly
affected potentially due to the effect of testosterone on the generation of interleukin-1
beta.
5
Overall risk of myocarditis and hospitalisation are lower in this age group after
vaccination compared with overall risk after SARS-CoV-2 infection without vaccination.
6
Data from the Clalit Health Services database in 2021 showed the immediate outcomes
of mRNA COVID-19 vaccine-related myocarditis based on a limited number of 54 patients
and reported a less than 5% risk of death or cardiogenic shock during or shortly after
hospitalisation.
7
Although acute myocarditis without signs of heart failure, ventricular arrhythmias,
or conduction system abnormalities is associated with a long-term favourable prognosis,
8
intermediate-term outcomes, specifically after vaccine-associated myocarditis in young
people, have not been reported. Furthermore, psychological and social sequelae of
myocarditis measured by patient-reported outcomes have not been reported in any form
of myocarditis.
In The Lancet Child & Adolescent Health, Ian Kracalik and colleagues
9
present detailed outcomes of mRNA COVID-19 vaccine-related myocarditis, including
clinical recovery, functional status, quality of life, and the results of cardiac
MRI, at least 90 days after diagnosis in patients aged 12–29 years. Using validated
survey tools, the authors obtained perspectives from adult patients or parents of
minor patients and from health-care providers. 519 (62%) of the 836 patients for whom
a report had been filed to the VAERS between Jan 12 and Nov 5, 2021, were surveyed.
No deaths were reported in the overall population. Among 357 patients with available
data, only six (2%) patients had a subsequent hospital admission; in three of these
patients, hospital admission was the result of iatrogenic adverse reactions to intravenous
immunoglobulin therapy. Only three (<1%) of the 357 patients were hospitalised for
cardiac causes: one due to reduction in left ventricular ejection fraction, one due
to chest pain and elevated troponin, and one due to pericarditis. A non-response bias
of 37·9% (317 patients out of 836) was potentially minimised by the observation that
major demographic characteristics and findings at presentation did not differ significantly
between survey responders and non-responders.
Among 393 patients with a health-care provider assessment, 320 (81%) were considered
to be fully recovered from myocarditis by their health-care provider, and 61 (16%)
patients were considered to be improved but not fully recovered. Only four (1%) patients,
out of 393 interviews, reported no change in cardiac status from the initial myocarditis
diagnosis. The median interval was 191 days (IQR 170–216) between myocarditis and
health-care provider surveys. In the patient survey, 178 (50%) of 357 patients reported
at least one symptom of chest pain, fatigue, dyspnoea, or palpitations in the 2 weeks
before the survey date (after a median interval of 143 days [131–162] from myocarditis
onset). Thus, adult patients, or parents of minors, perceived more symptoms of myocarditis
than did health-care providers. Health-care providers reported that only 62 (16%)
of 393 patients had one or more symptoms in the 2 weeks before the survey. This comparison
highlights the need to seek patient-reported outcomes rather than rely only on physiological
or biochemical metrics to identify full recovery.
Quality-of-life measurements revealed that, of 249 patients who completed this component
of the survey, 49 (20%) reported limitations in performing usual activities, four
(2%) reported problems with self-care, 13 (5%) with mobility, 74 (30%) reported pain,
and 114 (46%) reported depression. These findings emphasise the need to capture the
broad psychosocial effects of cardiac disease, particularly in a young and otherwise
healthy population. Notably, mean weighted quality-of-life measure was similar between
patients who had mRNA COVID-19 vaccine-related myocarditis (0·91) and pre-pandemic
US population norms (0.92; scale range 0 [equivalent to death] to 1 [full health]).
Further research is needed to determine whether restriction from physical activities
and sports, or the need to take medications, might have been contributing factors
in reported limitations in performing usual activities and depression.
10
Other psychological factors could have a role (eg, feeling of vulnerability after
a first experience of a serious health issue for most of the young individuals). Future
studies should assess how the psychological and physical injuries after mRNA COVID-19
vaccine-related myocarditis compare with those occurring after COVID-19-related myocarditis
in non-vaccinated people.
Finally, Kracalik and colleagues present novel data on post-myocarditis scarring,
defined by the presence of late gadolinium enhancement, and residual oedema on cardiac
MRI. In 151 patients with cardiac MRI, late gadolinium enhancement was observed in
71 (47%) patients and inflammation or oedema in 22 (15%) patients—rates that exceed
the rate of cardiac symptoms. For comparison, in a series of 190 patients (median
age 33 years, 82% male) with acute myocarditis and preserved left ventricular ejection
fraction,
11
cardiac MRI after 6 months showed scarring defined by the presence of late gadolinium
enhancement in 164 (86%) individuals and oedema in 31 (16%) individuals.
These data help to resolve the dilemma between vaccination and no vaccination: health-care
providers and individuals should be reassured by the high rate of cardiac recovery
in mRNA COVID-19 vaccine-related myocarditis. Nonetheless, the psychosocial burden
after a myocarditis diagnosis remains substantial and has been under-recognised. The
value of vaccination in protecting against SARS-CoV-2-associated acute myocarditis
and in lowering the risk of hospitalisation after SARS-CoV-2 exposure has been shown.
10
Kracalik and colleagues should be applauded because they, to our knowledge, are the
first to explore in detail the quality of life and impact of psychological symptoms
in young patients after acute myocarditis. Future prospective studies of myocarditis
should also include patient-reported outcomes to capture the full illness spectrum.
Patient Getting Vaccinated against COVID-19. Child, teenage boy vaccination. Coronavirus
epidemic. Copy space.
© 2022 Aja Koska/iStock
2022
EA has received a grant from the Italian Ministry of Health (GR-2019–12368506), and
is a consultant for Kiniksa and Cytokinetics. LTC has served as a consultant for Moderna,
receives grant funding from the National Institutes of Health, consults for Bristol
Myers Squibb, Kiniksa, Moderna, and CardiolRX, and is a board member of Stromal Therapeutics.