Studies Provide Interesting Results on Post-COVID Vaccination Myocarditis Cases

Co-published on Publish0x.

Introduction

At the beginning of December, I explained a possible mechanism for how the SARS-COV-2 vaccines can cause myocarditis.

To summarize in a few sentences, the virus can not only bind to the ACE2 cell receptor, but it can also bind to another receptor called CD147. In fact, you do not need the entire virus for the spike protein to bind to CD147 as the spike protein itself is sufficient. Heart cells and pericytes have a lot of CD147 receptors, so if the spike proteins get into the bloodstream, then the spike protein/C147 junction will cause the cell to release cytokines that recruit neutrophils and macrophages. In addition, host cell will also undergo apoptosis which will compromise the structural integrity of blood vessels and the myocardium.

While the prevalence of myocarditis among people who have received the vaccines is low, I emphasized at the end of my article that more research needs to be done. We will not get all the answers, but in time, the picture will become clearer. In fact, a study published on Nature Medicine has revealed some rather interesting results.

Myocarditis Post-Vaccination vs. Post-Infection

Patone et al. (2021) performed a case study of people in England who were vaccinated between December 1, 2020 to August 24, 2021. It investigated the frequency of hospitalizations or deaths from myocarditis, pericarditis, and heart arrhythmia in the 1 to 28 days after SARS-COV-2 infection or three vaccines: ChAdOx1 (AstraZeneca), BNT162b2 (Pfizer), and mRNA-1273 (Moderna).

The study found an increased risk of pericarditis and heart arrhythmia post-SARS-COV-2 infection whereas the three vaccines posed little risk. The myocarditis data, however, was different. When accounting for the entirety of the study population, testing positive for the virus posed the largest risk. Both the first and second doses of the Moderna vaccine yielded some excess events.

When Patone et al. (2021) looked at the incidence of myocarditis among patients younger than 40, it gets even more interesting. The second dose of the Moderna vaccine poses the largest risk among this age group. Getting infected with SARS-COV-2 yielded the second highest risk followed by the first dose of the Moderna vaccine. Both doses of the Pfizer vaccine also yielded some excess events.

The problem with this set of data is that it paints with a broad stroke. Certain diseases are more associated with certain groups whether they be men, women, young individuals or the elderly. For instance, heart attacks happen more frequently with men than women. There have been news of teenage boys suffering from heart inflammation or even die from particularly the second dose of either Pfizer or Moderna's vaccines. The question is whether that's just news overhype or if there's actually something going on.

Correlation Between Post-Vaccine Myocarditis, Age, and Sex

Witberg et al. (2021) recently published its study on The New England Journal of Medicine. The study analyzed Israeli data from the country's largest health care organization, Clalit Health Services. Over a 42 day period after the first dose of the Pfizer vaccine, the study measured the incidence rate of myocarditis amongst patients. Patients also received the second dose at a median of 21 days after the first dose.

The study found that the incidence rate rises at a much higher rate after the second dose than after the first dose. By Day 21, the incidence rate was about 0.5 myocarditis cases per 100,000 vaccinated people. By Day 42, the incidence rate rose to about 2 cases per 100,000 vaccinated people.

In addition, the study analyzed the incidence rates by sex, age, and age-sex. Males had a cumulative incidence rate of 4.12 per 100,000 whereas females only had a rate of 0.23 per 100,000. In terms of severity, males clocked an incidence rate of 3.15, 0.89, and 0.08 per 100,000 for mild, intermediate, and fulminant (severe) myocarditis, respectively.

When looking at age, people between 16-29 had an incidence rate of 5.49 per 100,000 with rates for mild, intermediate, and fulminant myocarditis at 4.29, 1.03, and 0.17 per 100,000, respectively. People older than 30 years have lower incidence rates across the board by a notable margin.

However, the data from males aged 16-29 were the most eye-opening. This cohort had a cumulative incidence rate of 10.69 per 100,000 with rates for mild, intermediate, and fulminant myocarditis clocking at 8.29, 2.06, and 0.34 per 100,000, respectively. These numbers easily outclass the incidence rates of other cohorts.

The Nature Study Adds Some Stratification

Due to demand for age and sex stratification, Patone et al. (2021) published a pre-print of its additional findings in December 25. The study differentiated its data based on males and females over/under 40 years of age. In addition, it added data for the 3rd doses, i.e. the booster shots.

The data from males under 40 corroborates what Witberg et al. (2021) found. Pfizer's second dose showed a slightly higher risk than testing positive for SARS-COV-2. Its booster shot yielded a higher incidence rate albeit with an extremely wide 95% confidence interval. Moderna's second dose yielded a higher risk and the difference is very likely to be significant as indicated by the lack of overlapping 95% confidence intervals with SARS-COV-2 infection. Moderna's booster shot showed no risk.

For females under 40, Moderna's second dose yielded higher risk than testing positive for SARS-COV-2, but the 95% confidence interval is extremely wide. For both males and females over 40, the risk of myocarditis is higher post SARS-COV-2 infection than post-vaccination of either AstraZeneca, Pfizer, or Moderna.

While this is a much appreciated addition, I think the study can afford to further stratify its data, especially on age. Above and below 40 are pretty broad and not as informative as, for instance, looking at groups of 16-24, 25-32, 33-40, and >40. Considering what Witberg et al. (2021) found with the Pfizer vaccine, I would not be surprised if the 16-24 male age group yielded the highest incidence rates.

It is also worth pointing out that the data for the SARS-COV-2 positive patients may be unreliable. The study collected the SARS-COV-2 infection data from the Second Generation Surveillance System. The flaw has little to do with the database being unreliable (in fact, it is). As Dr. Vinay Prasad pointed out in his Substack article, "the true number of infections is unknown. Many people don’t seek testing or medical care. So the red bar above will be shorter if you used a sero-prevalence (aka the correct) denominator".

In other words, the incidence rates for SARS-COV-2 infected patients is only based on known infections. However, the actual number of infected individuals is higher which may change the incidence rates and excess events per 100,000. The sero-prevalence Dr. Prasad is referring to measures the frequency of individuals in a population that has the SARS-COV-2 antigen. As a result, basing data on a robust sero-prevalence study would yield more accurate findings.

Closing Thoughts

While there is still a lot of work to be done, these studies answer a lot of questions regarding the risk of post-vaccination myocarditis. There are multiple ways to look at the data. While the risk of developing myocarditis rises after the second dose, the actual incidence rate is very small. On the other hand, for certain cohorts, the risk is greater after taking the second dose of Pfizer or Moderna than testing positive for SARS-COV-2. This is especially true for young men.

There is a lot of debate on whether the mRNA vaccines should be given to teenagers and children. While the absolute risk for myocarditis is low, the relative risk compared to getting infected with SARS-COV-2 is significantly greater. The effect becomes more pronounced amongst males and younger age cohorts. Moderna's second dose, in particular, does not look good after looking at Patone et al.'s (2021) pre-print. In fact, Germany actually recommends against Moderna for individuals under 30

Considering how much milder the Omicron variant is compared to previous strains, I think an intensive risk-benefit analysis should be done to determine the relative risks. On top of that, it would be nice for people to have more options on what type of vaccines they can take. The Novavax vaccine, for instance, is a "traditional" subunit vaccine. If people are uncomfortable with the mRNA vaccines due to certain associated symptoms like myocarditis, then the Novavax vaccine can fill that niche (provided that it's given the OK).