A preprint study finding that the Pfizer-BioNTech mRNA COVID vaccine is associated with an increased risk for cardiac adverse events in teenage boys has elicited a firestorm on Twitter. Although some people issued thoughtful critiques, others lobbed insults against the authors, and still others accused them of either being anti-vaccine or stoking the fires of the vaccine skeptic movement.
The controversy began soon after the study was posted online September 8 on medRxiv. The authors conclude that for boys, the risk for a cardiac adverse event or hospitalization after the second dose of the Pfizer mRNA vaccine was “considerably higher” than the 120-day risk for hospitalization for COVID-19, “even at times of peak disease prevalence.” This was especially true for those aged 12 to 15 years and even those with no underlying health conditions.
The conclusion — as well as the paper’s source, the Vaccine Adverse Event Reporting System (VAERS), and its methodology, modelled after the Centers for Disease Control and Prevention (CDC) assessment of the database — did not sit well with many.
“Your methodology hugely overestimates risk, which many commentators who are specialists in the field have highlighted,” tweeted Deepti Gurdasani, senior lecturer in epidemiology at Queen Mary University of London. “Why make this claim when you must know it’s wrong?”
“The authors don’t know what they are doing and they are following their own ideology,” tweeted Boback Ziaeian, MD, PhD, assistant professor of medicine at the David Geffen School of Medicine at UCLA, Los Angeles, in the cardiology division. Ziaeian also tweeted, “I believe the CDC is doing honest work and not dredging slop like you are.”
“Holy shit. Truly terrible methods in that paper,” tweeted Michael Mina, MD, PhD, an epidemiologist and immunologist at the Harvard T.H. Chan School of Public Health, Boston, more bluntly.
Some pointed out that VAERS is often used by vaccine skeptics to spread misinformation. “‘Dumpster diving’ describes studies using #VAERS by authors (almost always antivaxxers) who don’t understand its limitations,” tweeted David Gorski, MD, PhD, the editor of Science-Based Medicine, who says in his Twitter bio that he “exposes quackery.”
Added Gorski: “Doctors fell into this trap with their study suggesting #CovidVaccine is more dangerous to children than #COVID19.”
Gorski said he did not think that the authors were were anti-vaccine. But, he tweeted, “I’d argue that at least one of the authors (Stevenson) is grossly unqualified to analyze the data. Mandrola? Marginal. The other two *might* be qualified in public health/epi, but they clearly either had no clue about #VAERS limitations or didn’t take them seriously enough.”
Two of the authors, John Mandrola, MD, a cardiac electrophysiologist who is also a columnist for Medscape, and Tracy Beth Hoeg, MD, PhD, an epidemiologist and sports medicine specialist, told Medscape Medical News that their estimates are not definitive, owing to the nature of the VAERS database.
“I want to emphasize that our signal is hypothesis-generating,” said Mandrola. “There’s obviously more research that needs to be done,” he said.
“I don’t think it should be used to establish a for-certain rate,” said Hoeg, about the study. “It’s not a perfect way of establishing what the rate of cardiac adverse events was, but it gives you an estimate, and generally with VAERS, it’s a significant underestimate.”
Both Hoeg and Mandrola said their analysis showed enough of a signal that it warranted a rush to publish. “We felt that it was super time-sensitive,” Mandrola said.
Vaccine Risks vs COVID Harm?
The authors searched the VAERS system for children aged 12 to 17 years who had received one or two doses of an mRNA vaccine and had symptoms of myocarditis, pericarditis, myopericarditis, or chest pain, and also troponin levels available in the lab data.
Of the 257 patients they examined, 211 had peak troponin values available for analysis. All but one received the Pfizer vaccine. Results were stratified by age and sex.
The authors found that the rates of cardiac adverse events (CAEs) after dose 1 were 12.0 per million for 12- to 15-year-old boys and 8.2 per million for 16- and 17-year-old boys, compared with 0.0 per million and 2.0 per million for girls the same ages.
The estimates for the 12- to 15-year-old boys were 22% to 150% higher than what the CDC had previously reported.
After the second dose, the rate of CAEs for boys 12 to 15 years was 162.2 per million (143% to 280% higher than the CDC estimate) and for boys 16 and 17 years, it was 94.0 per million, or 30% to 40% higher than CDC estimate.
Mandrola said he and his colleagues found potentially more cases by using slightly broader search terms than those employed by the CDC, but agreed with some critics that a limitation was that they did not call the reporting physicians, as is typical with CDC follow-up on VAERS reports.
The authors point to troponin levels as valid indicators of myocardial damage. Peak troponin levels exceeded 2 ng/mL in 71% of the 12- to 15-year-olds and 82% of 16- and 17-year-olds.
The study shows that for boys 12 to 15 years with no comorbidities, the risk for a CAE after the second dose would be 22.8 times higher than the risk for hospitalization for COVID-19 during periods of low disease burden, 6.0 times higher during periods of moderate transmission, and 4.3 times higher during periods of high transmission.
The authors acknowledge in the paper that their analysis “does not take into account any benefits the vaccine provides against transmission to others, long-term COVID-19 disease risk, or protection from nonsevere COVID-19 symptoms.”
Both Mandrola and Hoeg told Medscape Medical News that they are currently recalculating their estimates because of the rising numbers of pediatric hospitalizations from the Delta variant surge.
Paper Rejected by Journals
Hoeg told Medscape Medical News that the paper went through peer-review at three journals, but was rejected by all three, for reasons that were not made clear.
She and the other authors incorporated the reviewers’ feedback at each turn and included all of their suggestions in the paper that was ultimately uploaded to medRxiv, said Hoeg.
They decided to put it out as a preprint after the US Food and Drug Administration (FDA) issued its data and then a warning on June 25 about myocarditis with use of the Pfizer vaccine in children 12 to 15 years of age.
The preprint study was picked up by some media outlets, including The Telegraph and The Guardian newspapers, and tweeted out by vaccine skeptics like Robert W. Malone, MD.
Rep. Marjorie Taylor Greene (R-Georgia), an outspoken vaccine skeptic, tweeted out the Guardian story saying that the findings mean “there is every reason to stop the covid vaccine mandates.”
Gorski noted in tweets and in a blog post that one of the paper’s coauthors, Josh Stevenson, is part of Rational Ground, a group that supports the Great Barrington Declaration and is against lockdowns and mask mandates.
Stevenson did not disclose his affiliation in the paper, and Hoeg told Medscape Medical News that she was unaware of the group and Stevenson’s association with it, and that she did not have the impression that he was altering the data to show any bias.
Both Mandrola and Hoeg said they are pro-vaccine and that they were dismayed to find their work being used to support any agenda. “It’s very frustrating,” said Hoeg, adding that she understands that “when you publish research on a controversial topic, people are going to take it and use it for their agendas.”
Some on Twitter blamed the open and free-wheeling nature of preprints.
Harlan Krumholz, MD, SM, the Harold H. Hines, Jr. professor of medicine and public health at Yale University, New Haven, Connecticut, which oversees medRxiv, tweeted, “Do you get that the discussion about the preprint is exactly the purpose of #preprints. So that way when someone claims something, you can look at the source and experts can comment.”
But Ziaeian tweeted back, “Preprints like this one can be weaponized to stir anti-vaccine lies and damage public health.”
In turn, the Yale physician replied, “Unfortunately these days, almost anything can be weaponized, distorted, misunderstood.” Krumholz added: “There is no question that this preprint is worthy of deep vetting and discussion. But there is a #preprint artifact to examine.”
Some clinicians signaled their support for open debate and the preprint’s findings.
“I’ve been very critical of preprints that are too quickly disseminated in the media, and this one is no exception,” tweeted Walid Gellad, MD, MPH, associate professor of medicine at the University of Pittsburgh School of Medicine. “On the other hand, I think the vitriol directed at these authors is wrong,” he added.
“Like it or not, the issue of myocarditis in kids is an issue. Other countries have made vaccination decisions because of this issue, not because they’re driven by some ideology,” he tweeted.
Gellad also notes that the FDA has estimated the risk could be as high as one in 5000 and that the preprint numbers could actually be underestimates.
In a long thread, Frank Han, MD, an adult congenital and pediatric cardiologist at the University of Illinois, tweets that relying on the VAERS reports might be faulty and that advanced cardiac imaging — guided by strict criteria — is the best way to determine myocarditis. And, he tweeted, “Physician review of VAERS reports really matters.”
Han concluded that vaccination “trades in a significant risk with a much smaller risk. That’s what counts in the end.”
In a response, Mandrola called Han’s tweets “reasoned criticism of our analysis.” He adds that his and Hoeg’s study has limits, but “our point is not to avoid protecting kids, but how to do so most safely.”
Both Mandrola and Hoeg said they welcomed critiques, but that they felt blindsided by the vehemence of some of the Twitter debate.
“Some of the vitriol was surprising,” Mandrola said. “I kind of have this naïve notion that people would assume that we’re not bad people,” he added.
However, Mandrola is known on Twitter for sometimes being highly critical of other researchers’ work, referring to some studies as “howlers,” and has in the past called out others for citing those papers.
Hoeg said she found critiques about weaknesses in the methods to be helpful. But she said many tweets were “attacking us as people, or not really attacking anything about our study, but just attacking the finding,” which does not help anyone “figure out what we should do about the safety signal or how we can research it further.”
Said Mandrola: “Why would we just ignore that and go forward with two-shot vaccination as a mandate when other countries are looking at other strategies?”
He noted that the United Kingdom has announced that children 12 to 15 years of age should receive just one shot of the mRNA vaccines instead of two because of the risk for myocarditis. Sixteen- to 18-year-olds already have been advised to get only one dose.
medRxiv. Published online September 8, 2021. Full text
Alicia Ault is a Lutherville, Maryland-based freelance journalist whose work has appeared in publications including JAMA, Smithsonian.com, the New York Times, and the Washington Post. You can find her on Twitter @aliciaault.
Source: Read Full Article