ORLANDO, Fla. — The Food and Drug Administration on Monday responded to the results of Florida Surgeon General Joseph Ladapo’s analysis of COVID-19 data that he says point to a risk for some men who get the shot.
Ladapo recommended against COVID-19 mRNA vaccines for men ages 18-39, a decision that contradicts the Centers for Disease Control and Prevention’s vaccine guidance and has invited confusion and criticism from the medical community.
The recommendation is based on a non-peer-reviewed analysis published Friday by the Florida Department of Health that found Floridians had an increased risk of cardiac-related death, but not overall death, in the 28 days after getting a COVID-19 shot. The risk was highest for men 18-39.
“We released an analysis on COVID-19 mRNA vaccines the public needs to be aware of. This analysis showed an increased risk of cardiac-related death among men 18-39,” Ladapo tweeted.
In response, federal government representatives reaffirmed their stance that the benefits of mRNA COVID-19 vaccines continue to outweigh potential risks for all age groups.
“This decision is flawed and a far cry from the science: COVID-19 vaccines have been proven safe and effective, and severe adverse reactions are rare,” said U.S. Department of Health and Human Services spokesperson Sarah Lovenheim in a statement. “Vaccines were evaluated in tens of thousands of participants in clinical trials and since then, tens of millions of Americans have received COVID-19 vaccines.”
Ladapo on Monday said he had received several criticisms about his study, including about its size, and offered a rebuttal.
“Even if the sample size was half of what it is, if events cluster after an exposure, that is valuable information about causation,” he tweeted.
Dr. Peter Marks, director of the Center for Biologics Evaluation and Research at the FDA, said the study’s results do not justify Ladapo’s recommendation.
The study did not find that COVID-19 vaccination was associated with more deaths overall, just that it was associated with a “modestly increased” risk of cardiac-related deaths.
“What’s so scary, so troubling to me, is that when you read the discussion, the discussion of the findings does not match with the action,” Marks said. “The discussion notes all of the weaknesses, including the fact that there’s not any decrease in all-cause mortality here.”
In contrast, the study found catching COVID-19 was associated with a “substantially higher” risk of both total deaths and cardiac-related deaths.
“From a public health perspective, I care about having more people alive at the end of the day,” Marks said. “The idea that, you know, that we’re going to have more people dead, but at least they won’t be dead of cardiac causes, I find that very challenging to understand. And that seems to be what’s being said here.”
The CDC warns that serious side-effects can occur after vaccination, but they are rare.
There appears to be a small risk of heart conditions known as myocarditis and pericarditis following vaccination, particularly in men 16 and older, the organization’s website states.
However, an August study of 43 million people in England found the risk of developing myocarditis due to COVID-19 is larger than the risk of developing it from vaccination.
“We know that our safety surveillance systems are working, because they do pick up safety signals,” Marks said. “We’ve continued to do these benefit-risk assessments, and they continue to be highly favorable, again, across all of the different age ranges ... including males 18-39.”
If evidence emerges that the benefits of Pfizer and Moderna no longer outweigh risks, the CDC would stop recommending them, just as it has stopped recommending the Janssen COVID-19 vaccine, Marks said.
University of South Florida associate professor Jason Salemi on Sunday called for a comparison of how many men between 18 to 39 died of COVID-19 during the study period.
“I have zero problems with these exploratory investigations. But they should lead to much better-designed studies that are comprehensive and actually seek better data before such sweeping recommendations are made,” he tweeted.
The Florida Department of Health’s study also had other limitations worth addressing, Marks added.
The unnamed authors of the paper note that because they determined causes of death from death records rather than medical records, they can’t be sure whether each of the deaths marked as cardiac-related was really cardiac-related.
As recently as September, a French peer-reviewed study looked at cardiovascular events in the country’s 46.5 million adults younger than 75 using medical records; this study found no relationship between cardiovascular events and Pfizer or Moderna vaccination.
Marks, a trained physician, said doctors sometimes label deaths as cardiac-related as a catchall.
“I wrote a lot of death certificates in my day. We tend to use a cardiac cause, like cardiopulmonary arrest, often when we don’t know what else is going on,” Marks said.
Others in the medical community levied the same criticism, to which Ladapo responded on Twitter. He said that though this was an “imperfect” way to determine cardiac deaths, it was a flaw in every subgroup the study examined and “only in young men was the risk extremely high.”
Marks added that the lack of transparency behind this study also troubles him.
It was not peer-reviewed and there are no authors listed. The Florida Department of Health did not respond to a request for comment on whether it plans to submit the data for peer review, nor did it share the names of the paper’s authors.
This analysis shouldn’t dissuade anyone from getting a vaccine, Marks said.
He added that he hopes this can start a discussion between representatives for the FDOH and the FDA.
“Our goal is not to get into like a fight or a tiff, because public health isn’t served well by this,” he said. “Our goal is to help get to ... an acceptance that there are overall benefits of these vaccines, despite the fact that yes, it is true that there could be some side-effects.”
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