Several recent publications have described myopericarditis cases after the coronavirus disease 2019 (COVID-19) vaccination. However, it is uncertain if these cases occurred secondary to the vaccination or more common etiologies of myopericarditis. To help determine whether a correlation exists between COVID-19 vaccination and myopericarditis, the present study compared the gender-specific cumulative incidence of myopericarditis and myocardial injury in a cohort of COVID-19 vaccinated patients at a tertiary care center in 2021 with the cumulative incidence of these conditions in the same subjects exactly 2 years earlier. We found that the age-adjusted incidence rate of myopericarditis in men was higher in the vaccinated than the control population, rate ratio 9.7 (p = 0.04). However, the age-adjusted incidence rate of myopericarditis in women was no different between the vaccinated and control populations, rate ratio 1.28 (p = 0.71). We further found that the rate of myocardial injury was higher in both men and women in 2021 than in 2019 both before and after vaccination, suggesting that some of the apparent increase in the diagnosis of myopericarditis after vaccination may be attributable to factors unrelated to the COVID-19 vaccinations. In conclusion, our study reaffirms the apparent increase in the diagnosis of myopericarditis after COVID-19 vaccination in men but not in women, although this finding may be confounded by increased rates of myocardial injury in 2021. The benefits of COVID-19 vaccination to individual and public health clearly outweigh the small potential increased risk of myopericarditis after vaccination.
A global push to create vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ultimately culminated in the issuance of Emergency Use Authorizations in the United States for the Pfizer-BioNTech and Moderna coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines in December 2020, followed thereafter by a similar issuance for the single-dose Janssen/Johnson & Johnson vaccine in February 2021. , As of July 2021, more than 187 million people received at least 1 dose of a COVID-19 vaccine and 162 million people were fully vaccinated in the United States. Potential side effects associated with the vaccine have been closely monitored by the Vaccine Adverse Event Reporting System. As of June 11, 2021, there were over 1,226 cases of myocarditis reported after an mRNA COVID-19 vaccine. A number of case reports and series have recently been published describing patients who experienced myocarditis after receiving the COVID-19 vaccination. However, it is uncertain if these cases may have been secondary to other etiologies of myocarditis like viruses, drugs, or autoimmune conditions, and only coincidentally occurred after COVID-19 vaccination. It is also unclear if the incidence of myocarditis observed is different than expected. Therefore, this study compared the gender-specific cumulative incidence of myopericarditis and of myocardial injury at a tertiary care center in a cohort of COVID-19 vaccinated patients from 2020 to 2021 versus the cumulative incidence of these conditions in the same subjects exactly 2 years earlier.
Methods
The vaccinated cohort consisted of all patients and employees of the Beth Israel Deaconess Medical Center (BIDMC) aged 18 years or older who were recorded in the Massachusetts Immunization Information System as having received at least 1 dose of a COVID-19 vaccine at a site within Massachusetts from August 3, 2020, to May 21, 2021. The control cohort consisted of the same subjects who were registered in the BIDMC electronic health records systems >2 years before their first COVID-19 vaccination date and were 18 years or older in 2019. The cohorts are listed in Table 1 . The vaccinated patients were followed from the date of their first COVID-19 vaccine dose to May 22, 2021. The control patients were followed from their anniversary date (exactly 2 years before their first vaccination date) to May 22, 2019.
| Variable | Vaccinated cohort (2020-2021) | Control cohort (2018-2019) |
|---|---|---|
| Total patients | 268,320 | 235,343 |
| Male | 107,750 (40%) | 94,546 (40%) |
| White | 156,906 (58%) | 142,635 (61%) |
| Asian | 31,154 (12%) | 27,924 (12%) |
| Black | 17,351 (6%) | 16,060 (7%) |
| Hispanic | 10,863 (4%) | 9,555 (4%) |
| Other | 13,404 (5%) | 11,263 (5%) |
| Unknown | 38,642 (14%) | 27,906 (12%) |
| Age (years) | ||
| 18-24 | 8,742 (3%) | 8,601 (4%) |
| 25-34 | 75,863 (28%) | 64,508 (27%) |
| 45-64 | 99,670 (37%) | 94,882 (40%) |
| ≥65 | 84,045 (31%) | 67,352 (29%) |
| Vaccine type | ||
| Pfizer-BioNTech | 145,698 (54%) | – |
| Moderna | 111,006 (41%) | – |
| Janssen/Johnson & Johnson | 11,499 (4.3%) | – |
| Average follow-up (days) | ||
| Mean ± sd | 73.5 ± 33.8 | 74.2 ± 33.4 |
| Median [IQR] | 71 [46-99] | 72 [47-100] |
| Maximum | 292 | 290 |
| Prior episode of care at BIDMC | 250,418 (93%) | 205,530 (87%) |
Patients evaluated in the inpatient or outpatient setting during the follow-up period with assigned International Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes consistent with myocarditis (I010, I011, I012, I090, I092, I30, I31, I32, I33, I38, I39, I40, I41, I514, and I21A1) were identified. Their medical records were scrutinized. Cases meeting the European Society of Cardiology’s diagnostic criteria for clinically suspected myocarditis or pericarditis of any possible etiology were classified as myopericarditis cases. , Patients with active COVID-19 infections and a history of myocarditis or pericarditis were excluded. The patients meeting the criteria for myopericarditis are detailed in Supplementary Appendix 1 . Similar ICD-10 search algorithms were used to identify patients diagnosed with myocardial infarction (MI). Acute appendicitis and acute pancreatitis cases were also identified using ICD-10 search algorithms to help establish if there were changes in health care utilization use after the post–COVID-19 surge. Cardiac troponin-T assays at the BIDMC are performed using the Roche ElectroChemiLuminescence ImmunoAssay. The 99th percentile in a healthy population for this assay is <0.01 ng/ml, and the threshold for acute MI using the traditional World Health Organization (Geneva, Switzerland) criteria is >0.10 ng/ml.
Continuous variables are summarized as mean ± SD or median with interquartile range. Statistical analyses were performed using SAS Studio 3.8 (SAS Institute Inc., Cary, North Carolina). Gender-specific age adjustment was performed using direct standardization using the STDRATE procedure in SAS using the annual estimate of the United States resident population for July 2019. Age-adjusted incidence rates and risks were compared using Mantel-Haenszel statistics. Cumulative incidence rates were calculated using Kaplan-Meier estimates and compared using the log-rank test. Categorical variables were compared using chi-square test. A p <0.05 was considered statistically significant, no adjustments were made for multiple comparisons. The study was approved by the BIDMC Committee on Clinical Investigations.
Results
There were 12 myopericarditis cases in the vaccinated group (6 men and 6 women; 2 pericarditis and 10 myocarditis/myopericarditis cases). A total of 3 cases occurred after the first dose of an mRNA vaccine (median 6 days after vaccine), 7 cases occurred after the second dose of an mRNA vaccine (median 4 days after vaccine), and 2 cases occurred after the single-dose Janssen/Johnson & Johnson vaccine (median 10 days after vaccine). There were 5 myopericarditis cases in the control group (1 man and 4 women; 4 pericarditis and 1 myocarditis case). The cases are detailed in the Supplementary Appendix 1 . No cases of myocarditis were seen in the 3.4% of the sample that was aged 18 to 24.
As depicted in Figures 1 and 2 , the age-adjusted incidence rate of myopericarditis in men was higher in the vaccinated group than in the control group (0.1170 per 100,000 person-days in the vaccinated and 0.0121 per 100,000 person-days in the control population, rate ratio 9.7 [p = 0.04]). In women, the age-adjusted incidence rate of myopericarditis was no different between vaccinated patients and controls (0.0420 per 100,000 person-days in the vaccinated and 0.0329 per 100,000 person-days in the control population, rate ratio 1.28 [p = 0.71]). Survival analyses showed a suggestion of a difference in the cumulative incidence of myopericarditis between vaccinated patients and controls in men (p = 0.08) but not in women (p = 0.66).
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