Last December, when Caleb Chung, a 12-year-old in Durham, North Carolina, first heard from his dad that he might be eligible for a local clinical trial of a COVID-19 vaccine, his reaction was a little muted. He was “interested,” he tells me over Zoom. Not excited, exactly, not jumping for joy at the thought of joining the rarefied ranks of the immune. Interested. He had heard about side effects, for one thing, while watching the news with his parents. But mostly he just wasn’t sure what to make of the idea.

So Caleb and his dad, a pediatrician who works with adolescents, started talking. They covered the science of creating vaccines and testing them and how trials had helped bring vaccines to vulnerable people in the past. Plus, Caleb missed seeing his friends indoors, and seventh-grade Zoom school was slow. Getting shots to more people would bring a quicker end to the tedium. So he signed up. In late December, he got his first shot of what was either the Pfizer-BioNTech vaccine or a placebo. Then, three weeks later, he received his second. Both times, he kept a daily log of how he was feeling, recording a slight fever and soreness in his arm on day two. He took it in stride. “I hope this means I got the vaccine,” he says.

At the moment, two COVID-19 vaccines have been greenlit for emergency use by the US Food and Drug Administration, but both are only available to people older than Caleb. The Moderna vaccine is authorized for people over 18, while Pfizer’s is allowed for people as young as 16 because people that age were included earlier in its trials. But that could be changing. Last week, Pfizer officials announced they had finished enrolling more than 2,200 people in an expanded vaccine trial that includes kids as young as 12, and Moderna is currently in the process of signing up teens. That likely sets the stage for the companies to include teens in their requests for FDA approval, expected later this spring.

In the difficult calculus of prioritizing who should receive scarce vaccines and when, children occupy a strange niche. The rate of deaths and hospitalizations is much lower for children than for other age groups, and there’s some—albeit sometimes conflicting—evidence that they may spread the virus at lower rates than adults. For a doctor faced with a decision between vaccinating an 80-year-old and a 15-year-old, the older person with the higher risk of severe illness would be the obvious choice, says Grace Lee, a professor of pediatrics at Stanford’s School of Medicine and a member of the CDC’s Advisory Committee on Immunization Practices. But there are plenty of reasons, she adds, why younger people should get the shots.

One factor is that every 15-year-old is different. Kids with preexisting conditions are prone to worse outcomes from COVID-19, just like adults, and many teens work outside of the home in fields like food service, an industry that has among the highest rates of infection. More than three-quarters of child deaths have been among Hispanic, Black, and American Indian children, and other effects of the disease, such as MIS-C, the immune ailment that sometimes trails in the wake of COVID-19 infection in children, have similar disparities. “We are understandably focused on deaths and hospitalizations, but we haven’t yet thought about the long-term effects,” Lee says. Without the option to vaccinate kids, a return to normal life—one that will inevitably involve less protective distancing and mask-wearing than we have now—would lead to the virus exacting a quiet but steady toll on children, she says. In October, the National Academy of Medicine recommended giving children the same vaccination priority as some essential workers based on a rubric that included equity.

Then there’s the role of people under 18, who make up about a quarter of the US population, in getting the nation to herd immunity. Just how many vaccinations are required to stop the free circulation of the virus will depend on just how well the shots reduce transmission, as well as illness. But getting 70 percent of the population vaccinated is a good rule of thumb. “If we are going to achieve the levels of community immunity that we need, excluding children is going to make that really, really challenging,” says Ann Chahroudi, director of Emory University’s Center for Childhood Infections and Vaccines.

“You need to go to a population where you know the two-dose strategy is not a big deal.”

Many existing vaccine campaigns follow that basic principle. The annual task of vaccinating against new influenza strains tends to result in patchy coverage among middle-aged adults, many of whom are loath to show up at a doctor’s office or pharmacy. But nearly two-thirds of children get vaccinated each year, protecting young and old alike. It’s also part of the thinking behind the pneumococcal vaccine: giving children the shot was found to be better at suppressing the spread of the bacteria among the elderly, who are at the greatest risk from it, than targeting those older people directly. Then there’s the rubella virus; the chief benefit of vaccinating children against it is to reduce the spread to pregnant women and their babies, who can have severe complications.

For maximum immune coverage, the younger the better. That’s because little kids routinely go to the doctor for check-ups and boosters. “You need to go to a population where you know the two-dose strategy is not a big deal,” says Sallie Permar, chair of pediatrics at Weill Cornell Medicine. She points to the hepatitis B vaccine, which requires three doses to reach maximal effectiveness. Even 12-year-olds can be difficult to get back to the doctor’s office multiple times in a row, so doctors aim to vaccinate kids who are younger.

This summer, Permar was among the experts raising the alarm at the limited planning for pediatric trials of a COVID-19 vaccine. She’s encouraged by the progress pharmaceutical companies have made since then and the possibility of more vaccines catching up. But even with the current timeline, it is difficult to imagine achieving what Permar had originally hoped for: vaccinating children at scale by fall. “I think we’re going to have to imagine schools this fall without kids being vaccinated,” she says.

But it’s important to think long-term, she adds. Vaccinations should hopefully quell the raging pandemic soon, but SARS-CoV-2 is likely to stay with us beyond that. Over time, antibodies from the current round of shots may wane, likely at different rates in different groups of people, and depending on which of the vaccines people initially receive. New variants have already prompted some vaccine makers to announce plans for retooled shots. But after the first round, people might be less motivated to get a boost—just like the annual flu-shot scenario. Kids would then play a role in keeping up immunity overall, helping to prevent outbreaks among other, more vulnerable populations.

Deescalation

Vaccines typically make their way into younger populations through a process called deescalation. Teenagers are the first rung on this ladder. Their immune systems are fairly mature, which means data about effectiveness and safety gathered from testing in adults translates to them smoothly. The primary aim of this phase of testing is to do a deeper dive into safety. Doctors like Lee are optimistic based on the data from adult tests, but drug companies need to be on careful watch for outliers—new or more abundant side effects or perhaps allergies and other immune ailments. After that comes the testing for children younger than 12, who during the trial process are often given lower initial doses, followed by another group that includes toddlers and infants.

In those later stages, the process often slows down. Convincing parents to enroll young children can be an arduous process, and scheduling their shots between other immunizations is a challenge. There’s also the possibility that the immune response might behave differently in young bodies, especially with different dose amounts. For infants, another complication is immunity potentially passed down from their mother. That protection helps keep the infant safe from infection but can prevent them from developing their own immune response if they receive a shot too early. (Researchers including Permar hope to study vaccinated women and their infants to help determine how soon that maternal immunity may wane.)

Moderna CEO Stephane Bancel told CNBC earlier this month that he expected trials for the under-12 group to take “much longer” than the ones for adolescent groups, and he doesn’t expect results until 2022, in part because of the dosing question. At a CDC meeting Wednesday, Emily Erbelding, director of the Division of Microbiology and Infectious Diseases at the National Institutes of Health, noted that all four of the leading vaccine candidates, including those made by AstraZeneca and Johnson & Johnson, have imminent plans to include teenagers in their trials, but none have a firm timeline yet for testing in younger children.

Hesitancy

In the meantime, the focus turns to uptake for those who will be vaccine eligible. In recent weeks, Chahroudi has been giving doses to elderly people at Emory who are grateful to receive a shot. But she knows it’s a self-selecting crowd. So she’s thinking ahead. In her own clinic, she’s made it a habit to ask her adolescent patients and their parents about the vaccines, knowing it’ll be the teens’ turn eventually. She has noticed some worrying patterns. “I’ve encountered a lot of hesitancy,” she says. “I don’t know that I’ve encountered one person who says they’re excited to get it.” As she probes into the reasons why, she often uncovers misinformation discovered online. People believe they can catch COVID from the vaccine (you can’t) or that corners were cut during development (they weren’t). But they also often wonder if vaccination will be more or less risky given their own medical history.

She can tell her young patients that their vaccination will benefit everyone, and she does. But first she wants to address their personal concerns, to share the science and data. Vaccine “hesitancy,” Chahroudi adds, isn’t really just a euphemism for those opposed to vaccines. It’s a sign of somebody who could benefit from learning a little more. “It’s a matter of individually taking the time and having a conversation with each person,” she says. It’ll be a long process, a lot of work for doctors like her. But Chahroudi hopes that when their time comes, it will mean people young and old will choose to protect themselves and others.

This story originally appeared on wired.com.

https://arstechnica.com/?p=1738385