Heart risk, data gaps fuel debate over COVID-19 boosters for young people | science

Florida Surgeon General Joseph Ladapo ignited a firestorm of outrage this month when, based on a state analysis showing that COVID-19 vaccines were linked to cardiac deaths in young men, he advised men ages 18 to 39 to stay away from the shots. Scientists slammed his warning for a lack of transparency and flawed statistics and rejected the eight-page analysis, which was anonymous and not peer-reviewed.

Still, the COVID-19 vaccines have a rare but worrisome cardiac side effect. Myocarditis, an inflammation of the heart muscle that can cause chest pain and shortness of breath, disproportionately affected older boys and young men who received the shot. Only one in several thousand in this age group is affected and recovers very quickly. A small number of deaths occurred Temporarily linked to vaccine myocarditis Across the world. But several new studies show that it can take months for the heart muscle to heal, and some scientists are concerned about what that means for patients in the long term. The US Food and Drug Administration (FDA) ordered vaccine manufacturers Pfizer and Moderna to conduct a study to assess these risks.

As they analyze emerging data and worry about knowledge gaps, scientists and doctors are divided over whether such concerns should affect vaccine recommendations, especially now that a new COVID-19 wave is coming and reformed boosters are hitting the scene. Almost all urge young people to be vaccinated with the first two vaccine doses, but the issue is more complicated with boosters. A key problem is that their benefits are unknown for the age group at highest risk of myocarditis, who are at lower risk of severe COVID-19 and other complications than older adults.

“I’m a vaccine advocate, I’d still vaccinate children,” says Jane Neuberger, a pediatric cardiologist at Boston Children’s Hospital who has cared for and studied patients with post-vaccine myocarditis. But Michael Portman, a pediatric cardiologist at Seattle Children’s Hospital who is studying the patients, said he wouldn’t hesitate to recommend boosters to healthy teenagers. “I don’t want to cause panic,” Portman says — but she wants 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 Risk of myocarditis or pericarditisInflammation of the tissue around the heart occurred in 1 in 6,700 boys aged 12 to 15 years after the second vaccine dose and in 1 in 16,000 after the first booster. Among 16- and 17-year-olds, it was one in 8000 after the second dose and one in 6000 after the first booster. Men aged 18 to 30 are also at slightly higher risk.

Many scientists suspect that vaccine-induced myocarditis is somehow triggered by an immune response after the COVID-19 shot. A German study was published last month New England Journal of Medicine It may be recommended driven by an inflammatory response SARS-CoV-2 binds to the spike protein, which causes the body to make the messenger RNA (mRNA) vaccine. The group reported finding specific antibodies in patients with vaccine-induced myocarditis and patients with severe COVID-19, which itself can cause myocarditis. The same antibodies, which interfere with normal inflammation control, were also seen in children who developed a rare, dangerous condition called multisystem inflammatory syndrome (MIS-C) after Covid-19. “I think it’s really another process,” said Karin Klingel, a cardiac pathologist at the University of Tübingen who helped lead the work. But it is still unclear whether the antibodies are directly causing myocarditis.

Most patients with post-vaccine myocarditis are hospitalized briefly and their symptoms subside quickly. Neuberger’s hospital tracked 22 patients who developed the condition, and he was largely reassured by their cures. Portman agrees: “A lot of these kids are asymptomatic after they leave the hospital.”

But what he sees in young people during follow-up appointments disturbs him: Although their heart rhythms are normal and they generally feel well, MRI scans of their hearts often show something called late gadolinium enhancement (LGE), which indicates muscle injury. . In June, Portman and his colleagues reported Journal of Pediatrics that 11 of 16 patients had LGE approximately 4 months after onset of myocarditis, although the area affected by the heart has shrunk since they were admitted to the hospital. This month, a CDC team reported that among 151 patients who had a cardiac MRI follow-up after 3 months, 54% had abnormalities, mostly LGE or inflammation.

How much to worry about chronic scarring in vaccinated patients is a question mark. Right now, it “doesn’t seem to be associated with adverse clinical outcomes,” said Peter Liu, chief scientific officer at the University of Ottawa Heart Institute. Still, “we’re tracking these patients” over time, Liu said, in a registry study of about 200 affected people across Canada so far. “We need long-term data to reassure us and the public,” agrees Hunter Wilson, a pediatric cardiologist at Children’s Healthcare of Atlanta, who supports boosters for youngsters. (He recently led a study that compared outcomes from vaccine-induced myocarditis, by COVID-19 itself and by MIS-C, which is available as a preprint and under journal review.)

The FDA requires six myocarditis studies each Pfizer And modern, makers of two mRNA vaccines. Neuberger, who is also interested in long-term data, co-led one of them in conjunction with the Pediatric Heart Network; The study, which Portman is also involved in, aims to begin recruiting 500 patients later this fall. Different studies will evaluate not only full-blown myocarditis, but also a shadow version called subclinical myocarditis, where individuals remain symptom-free.

Subclinical myocarditis may be more common than thought. Christian Müller, director of the Cardiovascular Research Institute at the University Hospital Basel, recently collected blood samples from nearly 800 hospital workers 3 days after they received a COVID-19 booster. None met 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 preexisting conditions could be attributed, but in the other 22 cases—2.8% of participants, female and male—Müller believed the vaccine caused the increase in troponin levels. The findings, which he presented at a meeting in August, align with a Recently published research from Thailand.

The good news: In both studies, troponin levels quickly returned to normal. And a brief troponin spike without symptoms doesn’t worry Müller: “If we’re healthy and we lose 1000, 2000 [heart muscle cells], it’s irrelevant,” he said. What worries him is the potential cumulative effect of annual boosters. “I am extremely concerned if we consider this to be a repeat incident.”

The big question is whether any risk to the heart, however small, is outweighed by the booster’s benefits. Young people are rarely hospitalized for COVID-19, but the virus is not without risk for them either. last year, A study of nearly 1600 college athletes Before vaccination found 2.3% of clinical or subclinical myocarditis after covid-19. Other chronic effects of infection include MIS-C and long covid. Studies in adults have shown that vaccination reduces the risk of chronic Covid by anywhere from 15% to 80%. “Because of that, I really think vaccination is worth it,” Liu said.

Mueller doesn’t: She’s happy her teenage daughters got their primary vaccine series but has no plans to get a booster. Paul Offitt, an infectious disease specialist at the Children’s Hospital of Philadelphia, thinks that if the goal is to prevent serious illness, healthy people under 65 need booster doses—and certainly not teenagers.

Countries are also split: in Switzerland, Germany and Denmark, the new bivalent boosters are mainly recommended for older adults and frail young people. In the United States, by contrast, the CDC now recommends that everyone age 5 and older, regardless of health history, get a booster.

Complicating the risk-benefit analysis is the ever-changing current of the epidemic. The Omicron, now the dominant variant, “seems a whole lot lighter” than its predecessors, Neuberger says. The CDC reported that as of 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 a lot less vaccine myocarditis now” than last year, Neuberger said. He doesn’t know why, but the trend may ease concerns about side effects. “Everything is a moving target.”

Uncertainty is frustrating — but that’s the story of the epidemic, says Walid Gelad, a physician who studies drug safety at the University of Pittsburgh: “We can learn what we need to know once we know.”