Pfizer finally publishes data on post-Covid vaccination subclinical myocarditis

Why I'm not that reassured

The much-anticipated study looking for subclinical myocarditis post vaccination has been published. This was a study the FDA required Pfizer complete as a post-marketing commitment when myocarditis became a recognized post-vaccination adverse event. A few people reached out to me to ask my take so I’m responding with Substack (P.S. sorry it’s been a while since I have written! Check out the podcast I just recorded with Jay Bhattacharya if you haven’t heard it yet)

The new investigation was just published in the journal Infectious Diseases and Therapy. This is a journal I have never heard of, which has a low impact factor of around 5. I’m not sure what to make of this.

The study was led by Timothy Albertson, MD, PhD Chair of Internal Medicine at UC Davis. He does not disclose any COIs in this paper

but apparently did receive a $4.1 million Pfizer grant in the 2022-2023 fiscal year.

Study Methods

In the interest of time, I’m going to limit my discussion to the the 12-30 year old study (Substudy B) since they have been found to be the high-risk group (with males 12-24 having myocarditis rates post-dose 2 mRNA of around 1/2,000-3,000 (1,2) and 13-18 year old males found to have subclinical myocarditis rates post-dose 2 Pfizer of around 3.5%). I’ve covered this all before on Sensible Medicine. I’ve also published peer reviewed papers on this topic as first and senior author (1,2).

Participants were randomized 1:1 to receive 1 vaccination (booster dose; see below) or placebo first, a month before before they received the opposite. High sensitivity troponin I samples were obtained before each vaccination/placebo, 4 days after vaccination, and once again at one month post-vaccination

It’s important to point out that, in order to qualify for this study, these young people were required to have already had 2 or 3 doses of Pfizer. See below:

So for the participants, this is their 3rd or 4th dose of a Pfizer! This introduces major selection bias because anyone that had myocarditis/myocarditis symptoms or any adverse event or severe reactogenicity from the first 2-3 doses would presumably not participate. These are also going to be generally “pro-vaccine” people who may be less inclined to report symptoms, though troponins obviously don’t lie.

For anyone claiming that this study “disproves” the Thai study finding a rate of subclinical myocarditis in 3.5% if males 13-18 post Pfizer dose 2, it does not. This is a different vaccine dose and a highly selective population.

Below is the flowchart of what happened to the 1487 randomized participants during the study. There was large dropout after vaccination/placebo. We should be given more details on whether the dropout occurred after vaccine or placebo, why these dropouts occurred, and what the adverse events were that led to dropout? A 2/1485 adverse event rate out of people who have previously not been found to be particularly reactive to the Pfizer vaccine is high. (also there is a typo in the table upper right “7534” but, even if the numbers are both 753/4, they seem to add up to more than the total 1487 who were randomized, which must be incorrect. (If it’s 734 in one arm, which would make sense numerically, then it’s not truly randomized)

Results

Below are the main results (per the authors). The first thing you might notice is almost all the participants are in both vaccine and placebo groups. Indeed the authors state they combined the groups. So, this must mean that half of the “placebo” group at pre-vaccine and day 4 had already received dose 1 a month earlier (could explain why those are higher! Correct me if I am wrong). And the 0.2% bump is sustained for at least a month in the vaccine group. The fact all participants are included in both groups and half in placebo were vaccinated a month ago is very confusing (one might even say misleading) and gets at why we need raw data and individual participant information to look at timing and amount of troponin elevation.

(Also there are more participants 4 days post than pre-vaccination, which again gets at a problem with record keeping here)

Edit 3/23/24

Fortunately for us (& if you didn’t believe me that the vaccine & placebo groups were combined above), the results were reported separately for the vaccine & placebo groups on the EU Clinical Trials Website about a month ago.

See below, but for the first vaccinated, the % w/ troponin elevations continued to rise through 1 month & 5 days:

0.7% —> 1.0% (5 days post vax dose1) —>1.1% (1 month post vax 1)—>1.5% (5 days post placebo dose)—>0.7% 2 months post-vaccination

For placebo group it went from

0.5% pre-placebo—>0.6% 5 days post placebo—»0.3% pre-vaccine —> 0.3% post-vaccination 1—>0.3% 1 month post-vaccination

So Arm 1 had an overall 0.8% troponin rise while arm 2 did not. What would be most helpful would be to have individual results of the participants to see if this was consistent with some participants experiencing sustained troponin elevations post-vaccination. It would also be nice to see how high the elevations were and if they corresponded with any symptoms.

Some non-reassuring & confusing individual results

They did provide some individual information in the Albertson et al publication.

7 participants had cardiac symptoms, 4 of which were post-vaccination and troponin levels were missing/not reported in three of these seven participants… weird.

One of the 1300ish participants who completed the study (see below) had cardiac symptoms, EKG changes and a new troponin elevation which was found to be related to the vaccine yet, the conclusion of the study was “These findings did not provide evidence that BNT162b2 causes troponin elevations.” (Except when it does, I guess?)

Then there’s this. There are clearly new elevations in troponin above 100 ng/L which were not present pre-vaccination. I have circled them in red.

These newly-elevated troponins of >100ng/L seem worthy of mention. How high exactly were those that were over 200ng/dL? Were the patients symptomatic? About 0.7% of the 12-17 year olds had new troponin elevations above 200 ng/L. Were they all males? (which would make it closer to 1.4%). Could they provide individual troponin levels and chronology as done in the Thai study?

So again, if 0.7% of 12-17 year olds have a new troponin elevation >200ng/L 4 days after vaccination, which was not there prevaccination, is that not evidence the vaccine may have been causal?

Authors’ concllusion appears incorrect

The conclusion “These findings did not provide evidence that BNT162b2 causes troponin elevations” appears incorrect. And this study was performed in a highly select subset of individuals who had already had 2-3 doses of Pfizer. People with previous mRNA reactogenicity/AEs would have been unlikely to participate in this study.

Especially considering the current lack of evidence of efficacy of these vaccines, I don’t get the same degree of reassurance the authors do, but it’s also basically their job to make the results sound reassuring since they are running this study for Pfizer.

Finally, I want to highlight again the fact the raw data are not available (particularly when this was an FDA requested study). The results should all be anonymized and made available for re-analysis. This should be expected and the standard.

I hope the authors or anyone else will comment with their thoughts, additions or corrections.

In Summary

• Undisclosed $4.1 million grant from Pfizer to the first author

• Selection bias w/all participants having received 2-3 pfizer doses in order to enter the study

• Clinical myocarditis rate 1/1500

• 2/1500 participants dropped out due to unspecified adverse events

• 3 participants with chest pain may have had missing troponins- no reason provided

• There were clearly new troponin elevations post -vaccination which were above 100 ng/L

• Authors combined vaccination and placebo arm results in a confusing & misleading way. Individual participant data should be provided

• The authors’ conclusion that Pfizer vaccination 3-4 in 12-30 does not cause elevated troponins appears to be incorrect

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I’ll leave you with some photos from my 13.5 mile 2,750ft vert run in the American Canyon. The weather is so beautiful right now!

Clementine Trail

View of No Hands Bridge from the Confluence

At the summit of the Culvert Trail

Running song of the day (bonus points if you tell me which awesome move this Swedish singer became famous for). Jag mår bra nu= “I’m doing fine now”