CDC Provides New Data on mRNA Vaccine Risk

One of the Pandemic Moving Targets

This post will be narrowly focused on the issue of the COVID mRNA vaccine’s risk for myocarditis and pericarditis (inflammation of the heart muscle and the surrounding sack of connective tissue). A clear understanding of this potential side effect is important for those of us concerned with the risk-benefit calculation of vaccinating young children. There was no signal of this complication during the initial randomized controlled trials of Pfizer and Moderna vaccine. It came to light as larger numbers of people were vaccinated, and the EUA indication and vaccination effort moved to the younger age group. Initially, we were hearing estimates of a very rare side effect on the order of 1-2/million. That number has slowly ratcheted up, first to 7-10/million, then following a large scale study of 9 million people in Israel the incidence in young males was found to be 13.7/ 100,000 or 137/M. Multiple studies around the world have confirmed that young teenage boys have the highest risk, and that the second shot carries more risk than the first. The reason the estimate of the frequency of myocarditis or pericarditis has gone up over time, is simply that as doctors became aware of this relatively infrequent event they began to look for it more rigorously and consistently, and not some nefarious effort to suppress information that might dissuade vaccination. Balanced against this vaccine cardiac side effect is the reality that COVID infection itself causes myocarditis and pericarditis in both young and old. We have been told for some time that by preventing disease the vaccine decreases the total number of myocarditis cases, but until now that statement was based on rather limited evidence.

Enter the CDC with the largest analysis to date comparing the incidence of infection related and vaccine caused cardiac side effects. Their main conclusions were that the risk of disease related myocarditis, pericarditis and MIS-C (Multi-organ System Inflammatory Syndrome) was 1.8-5.6 times the risk from vaccine in the age group most often experiencing this vaccine side effect, boys ages 12-17, and 6.5-8.3 times higher in young men ages 18-29. You might ask as I did, why does MIS-C which is a late inflammatory complication of COVID seen almost exclusively in children come into the analysis? I thought the point of the study was to compare the rates of vaccine and infection induced myocarditis and pericarditis. Actually the study was designed to compare the relative incidence of “cardiac involvement”, between vaccination and infection. Apparently the CDC’s reasoning is that MIS-C frequently causes some cardiac complications which should be taken into account. That involvement is not necessarily myocarditis/pericarditis, it can also include a toxic shock like picture with fever and hypotension, and other findings that are not myocarditis/pericarditis. The CDC states that “cardiac complications” occur in 80% of cases of MIS-C. That figure is taken from a study published in the NEJM early on in the pandemic in July 2020 and included 186 patient histories. Now this current CDC study is based solely on diagnosis codes, not chart reviews for extensive details. Considering it’s size that is totally understandable, however a look at their data tables show that a significant majority of the cases in the infection group were MIS-C and not specifically myocarditis/pericarditis. What I find curious is that they apparently included all those cases into the infection caused group, without knowing specifically whether they had myocarditis/pericarditis, or even any cardiac involvement. At the very least perhaps they should have taken a guess that 80% of this MIS-C group had “cardiac issues”. It appears to me that they are unfairly weighting the infection caused group. I have no doubt that even reducing the number of MIS-C cases counted in the infection caused group by 20% would have a significant effect on the confidence intervals. As it stands, for the 12-17 yo group, the lower limit of the confidence interval tells us the range of probable difference between vaccine and disease cardiac side effects may be as low as 1.8 times. According to the CDC statistical analysis they would not consider any relative risk less than 2 significant.

Now that I have risked complete reader boredom or sleep, I have to tell you that I think there is one more serious caveat to using this data to inform current decisions. This study looked at the period from January 2020 until January 31 2022. This of course was the time frame when virtually all COVID infections were caused by the original Wuhan strain, Alpha or Delta. It included only one month when Omicron was becoming prevalent. We know that Omicron, although very highly transmissible, is a milder infection than the previous strains. With a smaller percentage of people going to the ICU, requiring hemodynamic and invasive respiratory support, we can assume there is a significantly lower incidence of cardiac involvement. Anecdotally, this seems to be the case. It’s true that very young children have seen an increase in hospitalization rate, but indications are this is related to their relative inability to deal with a greater viral involvement of the airways by Omicron, and not myocarditis/pericarditis or MIS-C. The vaccine incidence of myocarditis remains the same in the Omicron era, but it is highly likely (but not yet proven) that the frequency of COVID caused cardiac effects is now lower. That would bring the relative risks closer together or perhaps even invert them. One further point, the benefit accruing from vaccination in preventing cases of cardiac complications presumably depends on the vaccine efficacy in preventing infection. That efficacy has tanked in the young thanks to Omicron. In my opinion this CDC study, which some are saying unequivocally answers the question of whether vaccination leads to fewer cases of “cardiac complications” than infection, leaves some significant questions open.

Now for the philosophy part. I said in my last post that I wasn’t giving advice on vaccinating young children, as I have done pretty commonly regarding adults. I will say it is clear to me that if you are dealing with a child who is compromised, immunologically, with chronic cardiopulmonary or congenital heart disease, chronic renal disease, diabetes, asthma or mentally, then that child should certainly be immunized. When it comes to the healthy, youngest in the 6mo-4yo age group, obviously we don’t know what the incidence of vaccine caused cardiac complications will be. We won’t know from the clinical trials in all likelihood, they don’t enroll sufficient numbers to parse very unusual complications. We could be optimistic that because the rate of myocarditis the CDC found in the 5-11 yo group was much lower than the 12-17yo’s, that a similarly low rate will be found in the youngest, but we don’t know. In my last post we looked at the potential benefit side of the equation, given the reduced vaccine efficacy in the younger age group now that Omicron has taken over. Thoughtful, informed, sophisticated thinkers could look at the data available so far and reach opposite conclusions about the desirability of vaccinating normal healthy young children at this time. Perhaps by now COVID has made us more comfortable with moving targets.