Results echo the controversial VAERS study from September
This article can also be found in medpagetoday.com
by Nicole Lou, Staff Writer, MedPage Today October 6, 2021
The incidence of myocarditis after receipt of the Pfizer-BioNTech COVID-19 mRNA vaccine was several times higher in two reports from Israel compared with some estimates, but remained low through the late spring of this year.
For patients in Israel’s largest healthcare system, Clalit Health Services, the estimate of myocarditis was 2.13 cases per 100,000 vaccinated persons, reaching as high as 10.69 cases per 100,000 in men and boys ages 16 to 29.
A separate study using Israel’s government database, capturing active and passive periods of surveillance for myocarditis, supported the higher risk in young men. In this report, males of all ages had myocarditis occur at 0.64 cases per 100,000 persons after the first dose and 3.83 cases per 100,000 after the second dose — with the incidence increasing to 1.34 and 15.07 per 100,000 after the first and second doses, respectively, for teenage boys ages 16 to 19.
Both papers were published online in the New England Journal of Medicine.
Differences in methodology — how myocarditis cases were counted and how far out from mRNA vaccination they would have to be to be considered post-vaccination cases — may account for the different estimates between the two studies.
These differences may also explain why these latest myocarditis estimates greatly exceed those from the CDC and a California health system. Notably, they are relatively closer to estimates in a controversial preprint study that had suggested post-vaccination myocarditis rates of 162 per million (16.2 per 100,000) in boys ages 12 to 15 and 94 per million (9.4 per 100,000) in boys ages 16 to 17 based on Vaccine Adverse Event Reporting System (VAERS) data.
In line with prior observations, the Israeli studies showed that the risk of post-vaccination myocarditis was greatest within a week after the second vaccine dose. Although cases were largely mild, there were deaths in these two reports.
Nevertheless, the latest data do not negate the previous finding that myocarditis is more common after SARS-CoV-2 infection than after vaccination.
Myocarditis in a Large Health System
The first Israeli study of the Clalit health system used electronic health record (EHR) data and cardiologist adjudication of these records.
Investigators counted 54 myocarditis cases within 42 days of receipt of a first dose of the Pfizer mRNA vaccine from Dec. 20, 2020 through May 24, 2021. The incidence of such inflammation varied according to age and sex.
- Overall population: 2.13 cases per 100,000 persons
- Men and boys: 4.12 per 100,000
- Women and girls: 0.23 per 100,000
- Young people ages 16 to 29: 5.49 per 100,000
- Men and boys ages 16 to 29: 10.69 per 100,000
- Individuals age 30 or older: 1.13 per 100,000
Of the 54 myocarditis cases, 41 were deemed mild and 12 were of intermediate severity. One person suffered cardiogenic shock that led to extracorporeal membrane oxygenation, according to a group led by Guy Witberg, MD, of Rabin Medical Center, Beilinson Hospital in Petah Tikva.
Follow-up lasted a median 83 days after myocarditis onset, during which one person with pre-existing cardiac disease died from an unspecified cause the day after discharge, and another with a history of pericarditis was readmitted to the hospital three times for recurrence (with no further myocardial involvement after the index hospitalization).
Witberg’s group counted more than 2.5 million Clalit patients who had received at least one dose of the Pfizer vaccine during the study period.
For cases identified from EHRs with enough data to satisfy CDC diagnostic criteria for myocarditis, cardiologists were brought in for adjudication. No biopsy was required for diagnosis.
The 54 people determined to have post-vaccination myocarditis had a median age of 27 years, and 94% were men. Two of them had contracted COVID-19 before vaccination.
A diagnosis of myocarditis occurred after the second mRNA vaccine dose in 69% of cases, with a median 21 days between the two doses.
Witberg and colleagues cautioned that the short follow-up in their report prevented them from drawing conclusions about the long-term prognosis of people with post-vaccination myocarditis. Furthermore, they couldn’t count cases from out-of-network hospitals where patients may have received care for myocarditis.
More Cases in a Government Database
In a separate study using a longer follow-up period, the Israeli government reported 136 definitive or probable cases of myocarditis across the country within 21 days after the first Pfizer dose and 30 days after the second dose.
Researchers led by Sharon Alroy-Preis, MD, MPH, of the Israeli Ministry of Health, calculated the incidence of myocarditis between the two mRNA vaccine doses.
- All men and boys: 0.64 cases per 100,000 persons after the first dose vs 3.83 per 100,000 persons after the second dose
- Males ages 16 to 19: 1.34 vs 15.07 per 100,000 persons
- Males ages 20 to 24: 1.91 vs 10.86 per 100,000 persons
- Males ages 25 to 29: 1.22 vs 6.99 per 100,000 persons
- Males ages 30 to 39: 0.41 vs 3.69 per 100,000 persons
- All women and girls: 0.07 vs 0.46 per 100,000 persons
Compared with historical data from 2017 to 2019, myocarditis was more than five times as likely after mRNA vaccination in the overall population. Compared with people who remained unvaccinated during the study period (from Dec. 20, 2020, to May 31, 2021), fully vaccinated individuals had about double the risk at 30 days after the second dose.
“The incidence of myocarditis declined as the number of newly vaccinated persons decreased over time. This finding was suggestive of a possible causal relationship between two doses of the vaccine and the risk of myocarditis,” wrote Alroy-Preis and colleagues.
People who had post-vaccination myocarditis had mild symptoms in 95% of cases. One person with fulminant myocarditis, a 22-year-old presenting with high elevated troponin T, died within 24 hours of receiving a myocarditis diagnosis.
Of the 136 cases of myocarditis, 95 were accompanied by sex and age data; 91% were male, and 76% were under the age of 30. Patients presented after the first vaccine dose in 19 cases and after the second dose in 117.
Like Witberg’s group, Alroy-Preis and colleagues acknowledged that they did not validate myocarditis cases with biopsies. Their study design also left room for ascertainment bias and confounding.
Witberg’s study was supported by a collaboration between Harvard Medical School and Clalit Research Institute.
Witberg and Alroy-Preis reported no disclosures.
New England Journal of Medicine
New England Journal of Medicine