Myocarditis after COVID-19 Vaccination

Sanjay Verma, MD FACC
15 min readJul 16, 2022

The Stupefying and Humbling True Magnitude

Image from Recognition and Initial Management of Fulminant Myocarditis

BACKGROUND

Myocarditis (inflammation of the heart muscle) can cause serious life-threatening complications (discussed in greater detail in previous publication). Numerous causes of myocarditis have been established, the leading cause being viruses. As noted in ACIP June 23 Update on Myocarditis following mRNA COVID-19 Vaccination, the background rate in the general population (before COVID pandemic) was about 8 cases per million in the pediatric population (0–18 years old), and 18 per million in 15–18 year-old adolescents. For adults, the rate gradually decreases with age. For both children and adults, the incidence is much higher in males than in females.

Update on Myocarditis Following mRNA COVID-19 Vaccination

During the past 2.5 years of the COVID-19 pandemic, both SARS-CoV2 infection and COVID-19 mRNA vaccines have been associated with myocarditis. Knowing the spike protein’s affinity to ACE2 receptors in the heart and spike protein’s injury to cardiomyocytes (cells of the heart), the association of myocarditis with SARS-CoV2 virus or spike protein-based mRNA vaccination was not unexpected. Initial reports from Israel of myocarditis after vaccination surfaced in April 2021. Public Health officials in US have continued to insist that myocarditis after SARS-CoV2 infection also occurs. They emphasize CDC’s analysis which erroneously concludes risk of myocarditis after SARS-CoV2 infection is greater than after mRNA COVID-19 vaccination. Currently, over 50,000 cases of myocarditis, pericarditis, or both are reported in VAERS. As the discussion below will demonstrate, the actual number of myocarditis cases may be 3–4 times greater than reported in VAERS and the rate after vaccination is greater than after COVID-19 infection.

OpenVaers

FDA granted EUA for mRNA vaccination against COVID-19 for those 6 months to 5 years old this past month. CDC now recommends vaccination against COVID-19 for everyone 6 months and older, regardless of risk stratification or prior infection with SARS-CoV2. Infection with SARS-CoV2 has been repeatedly proven to confer sustained and durable protection against COVID+ hospitalization and deaths.

https://twitter.com/CDCgov/status/1538557223424638979?s=20&t=46O4qjOVY-CyvZ3EYJ8Qzw

Using data mostly from passive surveillance data in VAERS (supplemented with data from Vaccine Safety Datalink, or VSD), CDC continues to emphatically assert that the COVID-19 vaccines are “safe and effective”. Repeated studies have shown rapidly decreasing vaccine efficacy (VE) in children and adolescents during the first few months after completing vaccination (here I discuss two recent studies demonstrating the decreasing VE in pediatric population). Adults also need repeated boosters due to rapidly diminishing protection over time. Despite the proven dramatic drop in VE over time, all of CDC’s risk benefit analysis (i.e, number needed to vaccinate to prevent one COVID+ hospitalization) are based on the orginal short term high VE. CDC extrapolates the original high VE as if it will be sustained, despite numerous studies demonstrating reduced VE within a few months. The decreasing VE then then begs the question if the benefits outweigh the risks in healthy children and young adults given the known increased, risk of myocarditis.

https://twitter.com/CDCDirector/status/1540021330589925378?s=20&t=NztKJ0Pe_a4-imcCBEyWuw

CDC ANALYSIS OF VACCINE ASSOCIATED MYOCARDITIS DEEPLY FLAWED

CDC’s analysis of Vaccine Associated Myocarditis (VAM) has been and repeatedly fatally flawed. CDC continues to use VAERS data alone in most of their meeting presentations despite prior studies demonstrating that VAERS underestimates the risk of myocarditis after vaccination by 3–4 times (when compared to insurance claims data or electronic health records (EHR) databases from hospitals. In another study comparing two methodologies even found that the CDC’s method of VSD analysis under estimated the risk of VAM. The FDA Summary Basis of Regulatory Action noted that the rate of VAM in VAERS was 40 cases per million doses, “while an FDA meta-analysis of four healthcare claims databases in CBER’s Biologics Effectiveness and Safety System estimated a rate of 148 cases per 1 million males 18 to 25 years of age vaccinated with the 2-dose primary series” (3.7 times greater than the rate determined from VAERS alone). For the cases of myocarditis after SARS-CoV2 infection, CDC uses officially confirmed PCR+ ‘cases’ (for the denominator), even though their own seroprevalence data demonstrates that far more people have been infected than officially conformed PCR+ ‘cases’. For example, seroprevalence data as of Feb 21, 2022 reveal 75% (about 54 million) of all children have been infected compared to 12 million officially confirmed PCR+ ‘cases’ (i.e., the actual number of kids infected is 4.5 times greater than PCR+ ‘cases’). Therefore, calculating the risk of myocarditis after SARS-CoV2 infection, the rate noted by CDC would need to be reduced by approximately 4.5 times for pediatric population. Thus far, CDC has not adjusted its COVID-19 morbidity and mortality data accordingly. CDC’s perfunctory refrain that most cases of VAM were “generally mild” based upon follow-up on VAM reports in VAERS will be critiqued separately (forthcoming) but has been briefly reviewed at the end of my previous publication.

STUDIES DEMONSTRATING THE TRUE INCIDENCE OF MYOCARDITIS MUCH HIGHER THAN CDC ESTIMATES

https://www.nature.com/articles/s41467-022-31401-5

In this peer reviewed French study, the authors evaluated national hospital discharge data for myocarditis after mRNA COVID-19 vaccination compared to unvaccinated controls. Compared to CDC’s reliance on VAERS this French study performs a more comprehensive analysis. The analysis indicates the risk of myocarditis after mRNA vaccination was 8 times greater than unvaccinated controls for BNT162b2 (Pfizer-BioNTech) and and 30 times greater than unvaccinated controls for mRNA-1273 (Moderna). By comparison history of SARS-CoV2 infection yielded a 9 times greater risk of myocarditis than controls.

Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines

Subgroup analysis by age and sex (supplementary appendix) found the risk of myocarditis in 18–24 year-old males to be 13 times and 44 times greater than unvaccinated controls for BNT162b2 and mRNA-1273, respectively (adjusting for prior myocarditis within past 5 years, deprivation index, and history of SARS-CoV2 infection within the past month). While much of the attention is given to adolescents and young adults (less than 30 years old), this study found the increased risk persisted in middle aged adult males also. For 30–39 year-olds, there was a 45 times greater risk after mRNA-1273 compared to unvaccinated controls, while 40- 50 year-olds had 21 times greater risk after mRNA-1273 compared to unvaccinated controls BNT126b2 was also associated with increased risk, but not to the same degree (see Table S2 below).

Supplementary Appendix to Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines

This study is limited by using hospital discharge diagnosis. In doing so, the study does not include those who may have died prior to hospitalization or those whose symptoms were not severe enough to be hospitalized. There have been reports of autopsy proven myocarditis after vaccination. There have also been anecdotal evidence of patients being dismissed by (Emergency Room) ER and never being hospitalized. In my own cardiology practice I have seen patents for VAM who were dismissed from the ER and never hospitalized. Adjusting for these excluded subsets may yield even higher risk than reported in this study. Follow-up of the patients in this study was limited to one month after discharge. Longer follow-up is warranted because persistent abnormalities on cardiac MRI are present in 75% of adolescents 3–8 months after COVID-19 mRNA vaccination.

Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada

Using population based passive surveillance from Ontario, Canada, this peer reviewed study assessed rates of reported myocarditis or pericarditis following receipt of a COVID-19 mRNA vaccines. As other studies have also found, the rate of myocarditis was greater in younger males than females, and greater after the second dose than after first dose. Data presented at CDC’s ACIP meeting June 23 and data from this preprint study (not yet peer reviewed) both found incremental increased risk of myocarditis after the booster; however, this study did not assess the rate of myocarditis after booster vaccination. No details are provided regarding presence of obesity or any other medical conditions on the patients in the study. Prior infection status is also not known about the study participants.

The study found myocarditis occurred at a rate of 97.3 per million doses of BNT162b2 (Pfizer) for 12–17-year-old males and 299.5 per million doses of mRNA-1273 (Moderna) for 18–24-year-old males. As the authors also mention in the discussion, this is substantially higher than the VAERS data reported by CDC (38.5 per million for mRNA-1273 doses in males and 69.1 per million BNT162b2 doses for males 16–17 years old). Furthermore, the authors continue, using data from four claims databases, FDA reported a rate of 283 cases of myocarditis per million of mRNA-1273 doses for males 18–25 years old. This is closer to the rate found in this study (299.5 per million). Vaccine Safety Datalink (VSD) data, the authors note, found the adjusted rate of myocarditis or pericarditis to be 2.72 times greater for dose 2 of mRNA-1273 than dose 2 of BNT162b2 (i.e, Moderna’s mRNA COVID-19 vaccine has almost 3 times the rate as Pfizer’s mRNA COVID-19 vaccine). CDC’s continued reliance on VAERS data alone for its risk-benefit analysis then is either incompetence or intentional data manipulation to control the narrative.

Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada

In response to questions about COVID-19 vaccine interchangeability (i.e., dose 1 and dose 2 are different COVID-19 vaccine manufacturers), CDC’s Interim Clinical Considerations state, “In exceptional situations in which the mRNA vaccine product administered for a previous dose(s) of the primary series cannot be determined or is not available, any age-appropriate mRNA COVID-19 vaccine product may be administered…” (empahsis mine). Regarding the booster, CDC’s recommendations state “Any age-appropriate mRNA vaccine can be used for the booster dose(s): it can be the same mRNA vaccine as the primary series (homologous booster dose) or a different mRNA vaccine (heterologous booster dose).” However, In the Supplementary Online Content of this study, the authors report that when vaccines are mixed (i.e., dose 1 and dose 2 are different manufacturers), the rate of myocarditis can be as high as 777 per million if mRNA-1273 is the second dose after initial BNT162b2 dose!!! The risk with heterologous dosing thus is 2.67 times higher than homologous dosing. The study found the risk to be considerably lower with longer interval dosing (i.e., longer than 30 days). Clearly, mixing vaccine manufacturers must be done with extreme caution with strong consideration for longer interval between dose 1 and dose 2.

Supplementary Appendix to Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada
https://jamanetwork.com/journals/jamacardiology/fullarticle/2791253

This Nordic cohort study followed 23 million residents 12 years and older from December 27, 2020 through October 27, 2021. “Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates forthe participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden.” Outcomes (myocarditis or pericarditis) were assessed by hospital discharge diagnosis and were limited to incidents occurring within 28 days of vaccination. The study is limited by hospital discharge diagnosis, not accounting for those who might died before hospitalization or not been hospitalized. Since spike protein has been found in circulation even four months after injection, limiting the study to outcomes within 28 days after vaccination may not capture the full extent of the morbidity.

The study found both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis across all ages 12 years and older. In biostatistics, the Incidence Rate Ratio (IRR) = Number of new cases during the follow up period / Total person-time by disease free individuals. The study found IRR for BNT12b2 was 2.04 (i.e., twice as many in the vaccinated group as the unvaccinated group) and 8.55 for mRNA-1273 (8 times as many incidents in the vaccinated group compared to the unvaccinated group). For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16–24 years) after the second dose (IRR 5.31 for BNT126b2 and 13.83 for mRNA-1273). The increased risk was not limited to adolescents and young adults; the IRR for 25–39 year old males was 12.96 (i.e., almost 13 times greater incidence in the vaccinated group compared to the unvaccinated group).

As in the study discussed above, heterologous dosing was associated with even high risk than homologous dosing. IRR was 35.62 for 16–24 year old males (compared to 13.83 for homologous dosing), and 23.13 for 25–39 year old males (compared to 12.95 for homolougous dosing) if mRNA-1273 was the second dose after first dose of BNT126b2. Heterologous dosing thus further increases the risk of myocarditis, yielding a risk 2.57 times greater for 16- 24 year old males and 1.78 times greater for 25–39 year old males. As noted above, mixing vaccine manufacturers must be done with extreme caution.

Overall, the study findings suggest between 40 and 70 excess events in 28 days per million vaccine recipients after BNT162b2, and between 90 and 280 excess events per million vaccine recipients after mRNA-1273. The authors conclude that “[t]his risk should be balanced against the benefits of protecting against severe COVID-19 disease.” Thus far, CDC does not seem to be balancing this risk with the putative benefits of COVID-19 vaccination in healthy children and young adults.

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents

The supplementary appendix notes a 4.8% all cause mortality within 28 days amongst all males (all age groups) in the study population who received 2 doses of mRNA-1273, presumably in those over 40 years old (i.e., none of the deaths occurred in those less 40 years old). As previously discussed here, animal models have shown an association with sustained aerobic exercise and increased risk of death. Because of this and the known association of myocarditis with sudden death in young athletes, current guidelines from the 2005 Bethesda Conference for activity with acute myocarditis recommend activity restriction from competitive athletics and other vigorous exercise for at least 6 months. Therefore, limiting all-cause mortality analysis to 28 days may be under estimating the true mortality risk.

Contrary to CDC’s repeated insistence that most cases of myocarditis after vaccination were “generally mild”, this Nordic study found 48% of all males (i.e., all age groups) were hospitalized longer than 3 days (i.e, discharged day 4 or later). All the males 16–24 years old were discharged within three days, whereas, only 60% of the males 25–39 years old were discharged within 3 days (i.e., 40% were discharged at day 4 or later). No details are provided on the percent requiring intensive care unit (ICU) care, pressor support (medications to support blood pressure in cardiogenic shock), or any persistent abnormalities on imaging. Furthermore, no data are available on 6-month follow-up of functional capacity (i.e., residual symptoms, exercise capacity).

Supplementary Appendix from SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab989/6445179

In a population cohort , this study from Hong Kong aimed at identifying all suspected cases of acute myocarditis in adolescents aged between 12 and 17 years who received the Comirnaty vaccine between June 14, 2021 and September 4, 2021. All suspected cases of acute myocarditis/pericarditis that occur within 14 days after receiving either the first or the second dose of the Comirnaty vaccine and admitted to one of the HA hospitals were reported to the Advanced Incident Reporting System (AIRS) on admission and the basis for this analysis. Vaccination records within the study period were extracted from the Department of Health (DH) in Hong Kong since the commencement of mass COVID-19 vaccinations in adolescents aged 12–17 years. Follow-up period was minimum 14 days. Patients with prior history of myocarditis / pericarditis were excluded. None of the reported cases had prior COVID-19 infection as evidenced by negative SARS-CoV2 PCR and nucleocapsid antibodies.

The study found 33 cases of myocarditis/pericarditis within 14 days following vaccination with Comirnaty. “All of them presented with chest pain. Three cases (9.09%) had normal troponin levels, 2 of them were cases of definite pericarditis and 1 had possible myocarditis. Six (18.18%) had normal ECGs, 25 (75.76%) had normal echocardiograms, and 7 (21.88%) had normal cMRI,” noted the authors. The incidence was higher in males than females, and found to be 322.9 per million. The incidence was even higher after second dose (373.2 per million) than first dose (55.7 per million). The study compared these rates to background incidence rate in 2020 and found the incidence rate difference to be 371.1 per million after second dose in adolescent males (Table 2 and Table 3 below). The incidence rates found in this study were much higher than CDC’s estimates based upon VAERS and even VSD.

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination
Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination

The study’s strength is its comprehensive analysis (all patients had imaging and laboratory evaluation, unlike many of the studies in the US where diagnostic evaluation for suspected VAM does not seem to be standardized). The authors acknowledge the study’s limitation in not capturing those with mild symptoms not leading to medical evaluation. The study does not enumerate the percent of patients needing ICU level care. No data are available on follow-up beyond 14 days.

MYOCARDITIS AFTER SARS-COV2 INFECTION

CDC continues to insist that COVID-19 can also cause myocarditis, that the incidence of myocarditis after SARS-CoV2 infection is greater than after vaccination, and that the benefits of COVID-19 vaccination outweigh the risks. CDC therefore recommends that all persons 6 months and older be vaccinated against COVID-19.

CDC MMWR on Cardiac Complications After SARS-CoV-2 Infection and mRNA COVID-19 Vaccination anlaysed EHR data from 40 health care systems, which is more comprehensive than VSD (9 integrated health systems) and certainly more comprehensive than passive reporting in VAERS. “Analysis of EHR data from 40 U.S. health care systems found that the incidences of cardiac complications after SARS-CoV-2 infection or mRNA COVID-19 vaccination were low overall but were higher after infection than after vaccination for both males and females in all age groups”, the MMWR concluded.

An egregious flaw in the study design is in how it defines the infection cohort: “persons who received ≥1 positive SARS-CoV-2 molecular or antigen test result”. CDC’s own seroprevalence data demonstrates that 75% of all children in the US have already been infected by SARS-CoV2. This data implies that 54 million children have already been infected, which is 4.5 times greater than the 12 million officially confirmed PCR+ ‘cases.

Nationwide COVID-19 Infection-Induced Antibody Seroprevalence (Commercial laboratories)

If the MMWR data on myocarditis after SARS-CoV2 infection were adjusted by 4.5 times (divided by 4.5), then the rate would be about half the rate of myocarditis after vaccination. This flaw in study design is not merely a ‘limitation’ of the study; it is a fatal flaw that stultifies the study and unequicoably nullifies the conclusions.

https://pubmed.ncbi.nlm.nih.gov/35456309/

In a retrospective cohort study of 196,992 adults after COVID-19 infection in Clalit Health Services members in Israel between March 2020 and January 2021 patients were followed for six months. “Inpatient myocarditis and pericarditis diagnoses were retrieved from day 10 after positive PCR. The control cohort of 590,976 adults with at least one negative PCR and no positive PCR were age- and sex-matched.” The study population has 27% obesity, whereas obesity prevalence in US is 42%. Thus caution must be applied in generalizing this study to US population.

The study found age (aHR 0.96; p =0.045) and the male sex (aHR 4.42; p = 0.003) were independently associated with myocarditis. Obesity was borderline associated with myocarditis (aHR 2.31; p = 0.053). Most notably, COVID-19 infection was not associated with myocarditis (aHR 1.08; 95% CI 0.45 to 2.56, p = 0.869). This study supports the interpretation above that findings from CDC MMWR ought to be adjusted seroprevalence data (i.e., infection cohort denominator needs to be adjusted by 4.5 times to account for the seroprevalence data). Without the adjustment for seroprevalence data, CDC erroneously concludes that myocarditis after SARS-CoV2 infection occurs at a greater rate than after vaccination.

The Incidence of Myocarditis and Pericarditis in Post COVID-19 Unvaccinated Patients — A Large Population-Based Study
The Incidence of Myocarditis and Pericarditis in Post COVID-19 Unvaccinated Patients — A Large Population-Based Study

SUMMARY

The background rate of myocarditis in general population is 8 per million for all children and 18 per million for 15–18 year old adolescents. Using primarily VAERS data, CDC estimates the risk of VAM to be about 40 per million. CDC’s own MMWR analyzing EHR from 40 health care systems found the rate to be 267 per million after second dose for 12–17 year old male. Other studies have found a rate of approximately 300 per million for 16–24 males after second dose of mRNA vaccination. The rate is further increased with heterologous dosing if mRNA-1273 is second dose within 30 days after BNT126b2 first dose (777 per million). The rates of VAM is in fact far greater than after COVID-19 infection when one adjusts for seroprevalence data in children. Continued insistence that everyone be vaccinated regardless of risk stratification or prior infection is an egregious affront to medical ethics and is dangerously jeopardizing the health and lives of children and young adults. School and college mandates ought to cease and desist immediately, lest we further unleash catastrophic mandated preventable harm.

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Sanjay Verma, MD FACC

Interventional Cardiologist (California), Medical Ethics, Philosopher