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Heart risks, data gaps fuel debate over COVID-19 boosters for youth | Science

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Florida Surgeon General Joseph Ladapo sparked outrage this month when he advised men ages 18-39 to stay away from vaccines, based on a government analysis that showed COVID-19 vaccines are linked to cardiac deaths in young men. Scholars harshly criticized his warning and condemned the eight-page analysis, which was anonymous and not peer-reviewed, for lack of transparency and inaccurate statistics.

Yet there is a rare but alarming cardiac side effect of COVID-19 vaccines. Myocarditis, an inflammation of the heart muscle that can cause chest pain and shortness of breath, hit vaccinated older men and younger men disproportionately. Only one in thousands of people in these age groups is affected, and most recover quickly. Worldwide, very few deaths have been tentatively associated with vaccine myocarditis. But a few recent studies suggest it may take months for the heart muscle to heal, and some scientists worry about what this means in the long run for patients. The U.S. Food and Drug Administration (FDA) has ordered vaccine manufacturers Pfizer and Moderna to conduct a series of studies to assess these risks.

As scientists and doctors parse emerging data and worry about knowledge gaps, they are divided over whether such concerns will impact vaccine recommendations, particularly as a new wave of COVID-19 emerges and renewed boosters come onto the scene. It encourages nearly all teens to get vaccinated with the first two doses of vaccine, but for boosters the situation is more complicated. A major problem is that its benefits are unknown for the age group at highest risk of myocarditis, who are at lower risk than older adults for serious COVID-19 and other complications.

“I’m a vaccine advocate, I would vaccinate kids anyway,” says Jane Newburger, a pediatric cardiologist at Boston Children’s Hospital who cares for and works with patients with post-vaccine myocarditis. But Michael Portman, a pediatric cardiologist at Seattle Children’s Hospital who also studies patients, says he would hesitate to recommend boosters to healthy teens. “I don’t want to panic,” Portman says—but he would like more clarity on the risk-benefit ratio.

Earlier this month, a team from Kaiser Permanente Northern California and the U.S. Centers for Disease Control and Prevention (CDC) reported that the risk of myocarditis or pericarditis (inflammation of the tissue surrounding the heart) is one in 6700 in 12-15. Year-old boys follow the second dose of vaccine, and approximately one in 16,000 following the first dose. In 16- and 17-year-olds, it was approximately one in 8,000 after the second dose and one in 6,000 after the first booster. Men between the ages of 18 and 30 also have a slightly higher risk.

Many scientists suspect that vaccine-induced myocarditis is somehow triggered by an immune reaction following the COVID-19 vaccine. A study published last month in Germany New England Journal of Medicine suggested that this may be driven by an inflammatory response associated with the spike protein of SARS-CoV-2 that messenger RNA (mRNA) vaccines have convinced the body to produce. The group reported that they found certain antibodies that can themselves cause myocarditis in both vaccine-induced myocarditis patients and severe COVID-19 patients. The same antibodies that interfere with normal inflammation control have also appeared in children who developed a rare, dangerous condition called multisystem inflammatory syndrome (MIS-C) after a COVID-19 attack. “I think it’s really just another mechanism,” says Karin Klingel, a heart pathologist at the University of Tübingen who helped lead the study. But whether antibodies directly cause myocarditis remains unclear.

Most patients with post-vaccine myocarditis are hospitalized for a short time and their symptoms subside rapidly. The Newburger hospital followed up on 22 patients who developed the condition and were largely reassured with their recovery. Portman agrees: “Many of these children are asymptomatic after they leave the hospital.”

But what he sees in the teens during follow-up appointments is troubling: Although their heart rhythms are normal and they generally feel fine, MRI scans of their hearts show something called late gadolinium enhancement (LGE), which often indicates muscle injury. . In June, Portman and colleagues Journal of Pediatrics Of the 16 patients, 11 had LGE approximately 4 months after the myocarditis episodes, although the affected area of ​​the heart had shrunk since their hospitalization. This month, a CDC team reported that 54% of 151 patients who had follow-up cardiac MRIs after 3 months had abnormalities, mostly LGE or inflammation.

It is a question mark how much to worry about the remaining scarring in vaccinated patients. Currently, this “does not appear to be associated with adverse clinical outcomes,” says Peter Liu, chief science officer at the University of Ottawa Heart Institute. However, in a registry study of nearly 200 affected people across Canada so far, “We’ve been monitoring these patients” over time, says Liu. “We need longer-term data to give us and the public confidence,” agrees Hunter Wilson, a pediatric cardiologist at Atlanta Children’s Healthcare and supports youth empowerers. (He recently led a study comparing the outcomes of vaccines, COVID-19 itself, and myocarditis caused by MIS-C, which is available as a preprint and is under journal review.)

The FDA requires six myocarditis studies from Pfizer and Moderna, makers of the two mRNA vaccines. Newburger, who is also keen on longer-term data, leads one of them in conjunction with the Pediatric Heart Network; The study, which includes Portman, aims to begin recruiting up to 500 patients this fall. Various studies will evaluate not only full-blown myocarditis, but also a shadow version, called subclinical myocarditis, in which individuals remain asymptomatic.

Subclinical myocarditis may be more common than previously thought. Christian Müller, director of the Institute for Cardiovascular Research at University Hospital Basel, recently collected blood samples from nearly 800 hospital workers 3 days after taking a COVID-19 booster drug. None met the criteria for myocarditis, but 40 had high levels of troponin, a molecule that can indicate heart muscle damage. In 18 cases, chronic heart problems and other pre-existing conditions could be blamed, but for the other 22 cases—2.8% of respondents, women and men—Müller believes the vaccine caused troponin levels to rise. His findings, which he presented at a meeting in August, match those of a recently published study in Thailand.

The good news: Troponin levels dropped to normal quickly in both studies. And a short symptomless increase in troponin does not concern Müller: “If we are healthy and lose 1000, 2000 [heart muscle cells]irrelevant,” he says. What worries him is the potential cumulative effect of annual boosters. “I’m very concerned if we consider this a recurring phenomenon.”

The big question is whether any risk to the heart, however minimal, outweighs the benefits of a booster. Teens are rarely hospitalized for COVID-19, but the virus is not without risk for them. Last year, a study of nearly 1,600 college athletes before vaccination 2.3% were found to have clinical or subclinical myocarditis after a COVID-19 attack. Other persistent effects of the infection include MIS-C and Long Covid. Research in adults shows that vaccination reduces the risk of Long Covid by anywhere from 15% to 80%. “So I think the vaccine is worth it,” Liu says.

Not Müller: She is happy that her teenage daughters are getting their first series of vaccines, but she has no plans to get them vaccinated. Paul Offit, MD, an infectious disease specialist at Children’s Hospital of Philadelphia, thinks there is little evidence that healthy people under 65 need boosters if the goal is to fend off serious illness – and certainly not adolescents.

Countries are also divided: in Switzerland, Germany and Denmark, new bivalent boosters are recommended especially for older adults and vulnerable youth. In the United States, by contrast, the CDC recommends empowerment for anyone age 5 and older, regardless of health history.

It is the ever-changing currents of the pandemic that complicates the risk-benefit analysis. Newburger says the now-dominant variant, the Omicron, “looks a lot softer” than its predecessors. The CDC reports that as of August, at least 86% of children in the United States are infected with SARS-CoV-2, which could reduce their risk of future infection. At the same time, Newburger says, “We’re now seeing a lot less of vaccine myocarditis than last year.” He doesn’t know why, but the trend may ease concerns about the side effect. “Everything is a moving target.”

The uncertainty is frustrating, but that’s the story of the pandemic, says Walid Gellad, a doctor in drug safety at the University of Pittsburgh: “Everything we need to know, we learn after we need to know.”