An interesting editorial published in the Journal of American Medical Association cardiology June 29th discusses this issue.
Two reports in the current issue the Journal of American Medical Association cardiology, described cases of acute myocarditis that occurred amongst patients who had received the Pfizer or Moderna RNA vaccines which are authorised for use in the United States. During the clinical evaluation of these patients, alternative aetiologies for myocarditis were not found.
The first report describes four cases of myocarditis with symptom onset one to five days after receipt of the second dose of the mRNA based COVID-19 vaccine to receive the Pfizer and to received the Moderna vaccine, who were evaluated in a single tertiary care Medical Centre.
Three cases occurred in men 23-36 and the fourth in a 70-year-old woman. All presented with severe acute chest pain, had abnormal electrocardiogram results, and had evidence of myocardial injury demonstrated by elevated troponin levels.
Cardiac magnetic resonance imaging was performed in these four patients on day three through five after vaccine receipt and the findings were consistent with acute myocarditis as defined by recent expert concession guidelines.
The second, larger case reports comes from the US Military Health System and describes 23 individuals with acute myocarditis who presented within four days after mRNA based COVID-19 vaccination.
All patients were male, 22 of 23 were on active duty, and the median range was 25.
20 cases occurred after receipt of a second dose of the mRNA COVID-19 vaccine.
Clinical presentations and laboratory findings were similar to those described in the smaller case series.
Eight of the 23 patients in this series received cardiac magnetic resonance imaging and all eight demonstrated findings again consistent with acute myocarditis.
A separate case report published by Marshall and others provides additional context in a younger population.
It reports seven US male adolescents aged 14 to 19 who presented with myocarditis or myopericarditis within four days after receiving the second dose of the Pfizer vaccine.
These adolescents were found to have elevated troponin levels, abnormal electrocardiogram results and findings on cardiac magnetic resonance imaging consistent with acute myocarditis.
No alternative aetiologies were found and the diagnosis was acute myocarditis suggesting an association with immunisation.
Interestingly, myocarditis or pericarditis was not detected in the clinical trials for these vaccines. However, it is possible that any association is too rare for recognition in the clinical trial enrolling less than several 100,000 participants.
The patients described in this US base case series had resolution symptoms or are recovering after receipt of brief supportive care and continue to be monitored during recovery from the acute illness.
So what is known about this possible association and immunisation?
Acute onset of chest pain three to five days after vaccine administration, usually after a second dose, was a typical feature of the reported cases and suggested an immune mediated mechanism.
Myocarditis following receipt of other vaccines is rare and is recognised as a causally linked only with smallpox immunisation. For example, myopericarditis has been reported in healthy adults after receipt of replication competent live vaccinia virus vaccines.
These highly reactogenic small pox vaccines differ dramatically by composition and by immunological responses compared with the mRNA based lipid nanoparticle vaccines currently in use for prevention of COVID-19.
We do not know the specific mechanisms by which immunological responses to mRNA based COVID-19 vaccines could lead to myocarditis.
Further investigation is critical and should be informed by the fact that most cases occurred following the second dose of a two dose series, some in patients with a history of prior COVID-19 infection.
We know the infection with SARS-CoV-2 can result in acute cardiac compromise in a substantial proportion of hospitalise patients, that it might lead to cardiac magnetic imaging findings suggestive of myocarditis in competitive college athletes with evidence of COVID-19, although the mechanisms that could lead to either direct SARS-CoV-2 viral injury or immunopathological injury of mycologist are unclear and under active investigation.
Myocarditis occurring after COVID-19 immunisation is very rare and has been estimated that of more than 560,000 persons in the six counties surrounding their tertiary care institution had received two doses of mRNA based COVID-19 vaccine by April 30th 2021 there were only four myocarditis cases detected by that date.
The Military Health System administered more than 2.8 million doses of mRNA based vaccine through April 30th 2021 and detected 23 myocarditis cases.
Based on the military’s extensive experience with vaccinia associated myocarditis, it is possible that the military system may be more likely to detect mild myocarditis cases than most civilian medical centres.
Amongst the 436,000 male active duty military who have received two mRNA vaccine doses, it is estimated that 0-8 cases of myocarditis might be expected based on the US data on the background evidence of the rate of myocarditis, once they detected 19 myocarditis cases in that group.
The most comprehensive data about the risks of myocarditis following immunisation with mRNA vaccines comes from Israel.
The Israeli Minister of Health recently posted data describing 121 myocarditis cases occurring within 30 days of a second dose of mRNA vaccine amongst 5049424 persons, suggesting a crude incident rate of approximately 24 cases per million following a second dose in this subset of their vaccinated population.
What can be concluded from this?
Cardiac injury after SARS-CoV-2 infection occurs and may result in severe outcomes.
Based on currently available data, myocarditis following immunisation with current mRNA based vaccines is rare.
At present the benefits of immunisation in preventing severe morbidity favours continued COVID-19 vaccination, particularly considering the increasing COVID-19 hospitalisation rates amongst adolescents reported during spring 2021.
Clearly there are various questions that need to be answered. Should there be modifications to the vaccine schedule?
If any, should a person with a history of possible confirmed myocarditis after the first dose of COVID-19 vaccine have the second?
How should post vaccine myocarditis be managed, particularly given the apparently benign outcomes which have been described and the success of supportive or conservative management alone?
How often should follow up assessments, including repeated cardiac imaging be performed in these patients and how might follow up assessments affect recommendations to avoid vigorous physical activity following the diagnosis of myocarditis?
Do all likely cases of acute myocarditis that appear to be uncomplicated require cardiac MRI imaging for more definitive diagnosis?
This is obviously an evolving story but here at The London General Practice, the leading London doctors’ clinic, we work closely with leading cardiologists to look at this issue and provide a full diagnostic and management service.
Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed