Myocarditis as Metaphor for COVID-19 Vaccine Risk-Benefit Calculation

Most COVID-19 vaccine hesitant patients are fearful of the reported risks as well as any potential as-yet-undiscovered side effects of the vaccine. When talking to a COVID-19 vaccine hesitant patient, I think it is fair to tell them that given how contagious the delta variant is, within 6 months they are most likely to either to get the disease or the vaccine (and some may get both). We should make it clear that they need to weigh the risks of vaccine receipt with the risks of contracting COVID-19 instead of looking only at the vaccine risks. In other words, which is riskier, COVID-19 disease or the vaccine?

A closer look at the risk of myocarditis following COVID-19 vaccination is instructive when it comes to helping a patient calculate a risk/benefit ratio.

Myocarditis has been described following administration of the second dose of both mRNA vaccines. Which of the following statements about this is NOT true?

a. About 500 cases of myocarditis have been reported as of the end of June 2021.
b. Over all ages, the risk is about 1 in a million.
c. The risk in the 18- to 28-year-old age group is about 17 in a million.
d. The risk is basically the same for men and women.

According to a presentation given at the July 5, 2021, Advisory Committee on Immunization Practices (ACIP) meeting, called to address the COVID-19-19 vaccine risk concerns, option d is the false statement. Up until age 49 years, men are at a much higher risk for myocarditis than women:

• Men aged 18-29 years: 8-fold higher risk vs women
• Men aged 30-49 years: 3- to 4-fold higher risk vs women

Over age 50, when the risk drops to <1 in a million, there is no difference in myocarditis risk observed between the sexes. The risk to a man in the 18- to 29-year-old age group is 24 in a million vs 6 per million for those aged 30- to 49-years.

Myocarditis risk in youths aged 12- to 18-years

Parents of adolescents are appropriately fearful of the reports of myocarditis following, in particular, the second shot. Youths aged 12- to 18-years are now eligible for COVID-19-19 vaccines, but the CDC did not present any data on vaccine-related myocarditis in this age group at their last meeting.

The rate of myocarditis may be higher and the risk of disease lower in the 12- to 18-year age group.

Researchers in the state of Washington looked at cases of myocarditis in their state occurring within 1 week following receipt of the second COVID-19 vaccine dose. They calculated a risk of 80 per million in the 16- to 17-year-olds and 100 per million in the 12- to 15-year-olds. This averages out to 90 cases of myocarditis which would result in about 90 hospitalization and zero deaths.

Compare this to the risk of COVID-19 disease per million. The risk to the unvaccinated cohort is estimated by the CDC to be about 200 hospitalizations and 1.5 deaths in the 12- to18-year age group. The vaccine has a real risk, but the risk from COVID-19 is greater.

Myocarditis risk in those aged 18- to 29-years-old

Lets look at the CDC estimates of risk comparison in the 18- to 29-year-old cohort. As with the adolescents, the main serious risk to those receiving the vaccine appears to be the development of myocarditis. No one has died from myocarditis following vaccination, but most have been hospitalized.

If we look at the risk per 1 million second doses of mRNA vaccine, about 22-27 cases of myocarditis would be expected in the group. Long term sequelae are unknown. What is the risk of COVID-19 disease complications in this age group versus the 22-27 myocarditis cases from the vaccine?

Consider a cohort of 1 million unvaccinated men aged 18- to 29-years who contract COVID-19. Which of the following statements is NOT true?

a. 300 hospitalizations would occur
b. 60 ICU admissions would occur
c. No deaths would occur
d. More females in the same age group would need hospitalization vs the men.

It is not true that no deaths would occur, option c. An estimated 3 deaths from COVID-19 would occurring this age group of unvaccinated men. While there would have been only an estimated 3 to 4 cases of myocarditis among women in this age group, they tend to fare worse with COVID-19 disease. The CDC estimates that the group of unvaccinated 18- to 29-year-old women would have 750 hospitalizations, 50 ICU admission and 5 deaths.

Compare the above 300 hospitalizations, 60 ICU admissions, and 3 deaths in an unvaccinated group of a million with the risks to a vaccinated cohort of the same number where about 25 would be hospitalized from myocarditis and no deaths.

Myocarditis in the Big Ten Athletic Conference

COVID-19 disease also causes myocarditis. A study published in JAMA Cardiology looked at data from The Big Ten Athletic Conference where all athletes who tested positive for COVID-19 were evaluated intensively, including with cardiac MRIs, for myocarditis.

Of the 1,597 evaluations, what percent had evidence of myocarditis? (Remember, the highest risk from vaccine-caused myocarditis seen in male youth aged 12- to 15-years is 0.01%.)

a. 0.05%
b 0.01%
c. 0.1%
d 2.3%

The correct answer is d. 2.3%. Two-thirds (76%) of the students with myocarditis in this intensively investigated group had no cardiac symptoms. To be fair, we do not know how many adolescents would test positive for myocarditis following vaccination with intensive testing since only symptomatic cases are being documented.

So why are only 50% of Americans fully vaccinated?

Ask your patient what his concerns are. If it is “vaccine safety,” agree with them that the vaccines are not 100% safe, but get the conversation shifted over to the COVID-19 disease risk compared to the small, but real, vaccine risk.

If they voice concern over the “as-yet-undiscovered” long term side effects of the vaccine, I would agree and also point out that we don't yet know all the “as-yet-undiscovered” side effects of COVID-19 disease.

In general, humans overestimate the likelihood of rare events occurring (which is why lotteries survive). Risk described as a number is difficult to understand, but comparison of 2 risks, side-by-side, is easier to understand. “Your risk of myocarditis after your second shot is 90 in a million,” is less meaningful than “You are twice as likely to need hospitalization if you don't get the shot than if you do.”

Sources:

COVID-19 Vaccines in Adults: Benefit-Risk Discussion, ACIP Meeting, July 22, 2021

Schauer J, et al. Myopericarditis after the Pfizer mRNA COVID-19 vaccine administration. J Peds. Published online July 2, 2021. DOI:https://doi.org/10.1016/j.jpeds.2021.06.083