Heart risks and data gaps fuel debate over COVID-19 boosters for young people | Science

Florida Surgeon General Joseph Ladapo sparked a furor this month when, based on a state analysis purporting to show COVID-19 vaccines were linked to cardiac deaths in young men, he advised men between the ages of 18 and 39 to avoid beatings. Scientists criticized his warning and decried the eight-page analysis, which was anonymous and not peer-reviewed, for its lack of transparency and flawed statistics.

Yet COVID-19 vaccines have a rare but concerning cardiac side effect. Myocarditis, an inflammation of the heart muscle that can cause chest pain and shortness of breath, disproportionately struck older boys and young men who received the injections. Only one in several thousand in these age groups is affected, and most feel better quickly. A small number of deaths have been tentatively linked to vaccinia myocarditis around the world. But several new studies suggest heart muscle can take months to heal, and some scientists are concerned about what this means for long-term patients. The US Food and Drug Administration (FDA) ordered vaccine makers Pfizer and Moderna to conduct a series of studies to assess these risks.

As they analyze emerging data and worry about knowledge gaps, scientists and doctors are divided on whether these concerns should influence vaccine recommendations, especially now that a new wave of COVID- 19 is looming and revamped boosters are appearing. Almost all recommend vaccinating young people with the first two doses of vaccine, but the case of boosters is more complicated. A key issue is that their benefits are unknown for the age group most at risk for myocarditis, who are less at risk for severe COVID-19 and other complications than older adults.

“I’m a vaccine advocate, I would always get kids vaccinated,” says Jane Newburger, a pediatric cardiologist at Boston Children’s Hospital who has treated and studied patients with post-vaccination myocarditis. But Michael Portman, a pediatric cardiologist at Seattle Children’s Hospital who also studies patients, says he would be hesitant to recommend boosters for healthy teenagers. “I don’t want to cause panic,” Portman says, but he needs more clarity on the risk-benefit ratio.

Earlier this month, a team from Kaiser Permanente Northern California and the US Centers for Disease Control and Prevention (CDC) reported the risk of myocarditis or pericarditis– inflammation of the tissues surrounding the heart – was about one in 6,700 in boys aged 12 to 15 after the second dose of vaccine, and about one in 16,000 after the first booster. Among 16- and 17-year-olds, it was about 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 somewhat elevated risk.

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

Most patients with post-vaccination myocarditis are hospitalized briefly and their symptoms improve quickly. Newburger Hospital has followed 22 patients who developed the disease, and she is largely reassured by their recovery. Portman agrees: “Many of these children are asymptomatic after leaving the hospital.”

But what he sees in young people at follow-up appointments nags him: Although their heart rhythms are normal and they generally feel fine, MRIs of their hearts often show something called late gadolinium enhancement ( LGE), which means muscle injury. . In June, Portman and colleagues reported in The Journal of Pediatrics this 11 of the 16 patients had LGE approximately 4 months after their episode of myocarditis, although the affected area in the heart has shrunk since their hospitalization. This month, a CDC team reported that among 151 patients who underwent a follow-up cardiac MRI after 3 months, 54% had abnormalities, mostly LGE or inflammation.

How much worrying about persistent scarring in vaccinated patients is a question mark. At present, this “does not appear to be correlated with adverse clinical outcomes,” says Peter Liu, scientific director of the University of Ottawa Heart Institute. Still, “we’re following these patients” over time, Liu says, in a registry study of about 200 affected people across Canada so far. “We need longer-term data to reassure ourselves and the public,” agrees Hunter Wilson, a pediatric cardiologist at Children’s Healthcare in Atlanta who supports recalls for young people. (He recently led a study comparing the outcomes of vaccine-induced myocarditis, COVID-19 itself, and MIS-C, which is available in preprint and under review review.)

The FDA requires six myocarditis studies each of Pfizer and Modern, the makers of the two mRNA vaccines. Newburger, who also wants longer-term data, co-leads one in collaboration with the Pediatric Heart Network; the study, in which Portman is also involved, aims to begin enrolling up to 500 patients later this fall. The various studies will assess not only full-fledged myocarditis, but also a phantom version called subclinical myocarditis, in which individuals remain symptom-free.

Subclinical myocarditis may be more common than you think. Christian Müller, director of the Institute for Cardiovascular Research at University Hospital Basel, recently took blood samples from nearly 800 hospital workers 3 days after receiving a COVID-19 reminder. None met the criteria for myocarditis, but 40 had elevated levels of troponin, a molecule that can indicate heart muscle damage. Chronic heart problems and other pre-existing conditions might be to blame in 18 cases, but for the other 22 cases – 2.8% of participants, both women and men – Müller believes the vaccine caused an increase in troponin levels. The findings, which he presented at a meeting in August, align with those of a recently published study in Thailand.

The good news: In both studies, troponin levels quickly fell to normal. And a brief troponin spike without symptoms is not about Müller: “If we’re healthy and we lose 1,000, 2,000 [heart muscle cells], it’s irrelevant,” he says. What worries him is a possible cumulative effect of the annual boosters. “I am very concerned if we consider this to be a recurring phenomenon.”

The big question is whether any risk to the heart, however small, is outweighed by the benefits of a booster. Young people are rarely hospitalized with COVID-19, but the virus is not without risk for them either. Last year, a study of nearly 1,600 college athletes before vaccination found 2.3% had clinical or subclinical myocarditis after an episode of COVID-19. Other lasting effects of infection include MIS-C and Long Covid. Studies in adults suggest that vaccination reduces the risk of Long Covid by 15% to 80%. “Because of that, I really think vaccination is worth it,” Liu says.

Müller doesn’t: He’s glad his teenage daughters got their first round of shots, but has no plans to give them a booster shot. Paul Offit, an infectious disease specialist at Children’s Hospital of Philadelphia, thinks that while the goal is to avoid serious illness, there is little evidence that healthy people under 65 need a booster dose, and certainly not teenagers.

The countries are also divided: in Switzerland, Germany and Denmark, the new bivalent boosters are mainly recommended for the elderly and the youngest vulnerable. In the United States, on the other hand, the CDC now recommends that everyone aged 5 and over, regardless of their medical history, should be boosted.

The ever-changing currents of the pandemic complicate the risk-benefit analysis. Omicron, now the dominant variant, “seems much milder” than its predecessors, says Newburger. The CDC reports that in August, at least 86% of children in the United States have been infected with SARS-CoV-2, which may reduce their risk of future infections. At the same time, “we’re seeing so much less vaccinia myocarditis now” than last year, says Newburger. She’s not sure why, but the trend might ease concerns about side effects. “Everything is a moving target.”

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