Theo, an 18-month-old in rural Nebraska, walks with his father in their backyard. For many toddlers, the barriers to accessing COVID-19 vaccines are many, such as few locations giving vaccines to very young children.
It’s Theo’s* first time in the snow. Wide-eyed, he totters outside holding his father’s hand. Sarah Holmes feels great joy in watching her 18-month-old son experience the world, “His genuine wonder and excitement gives me so much hope.”
In the summer of 2021, two months after Theo was born, Holmes, a behavioral health provider in Nebraska lost her grandparents to COVID-19. Both were vaccinated and thought they could unmask without any risk. “My grandfather was a veteran, and really trusted the government and faith leaders saying that COVID-19 wasn’t a threat anymore,” she says.” The state of emergency in Louisiana had ended and that was the message from the people they respected. “That is what killed them.”
The current official public health messaging is that regardless of what variant is circulating, the best way to be protected is to get vaccinated. These warnings no longer mention masking, or any of the other Swiss-cheese layers of mitigation that were prevalent in the early days of this ongoing pandemic.
The problem with the prevailing, vaccine centered strategy is that if you are a parent with children under five, barriers to access are real. In many cases, meaningful tools and changes that would address these obstacles are lacking, such as offering vaccines at more locations, mandating masks at these sites, and providing paid leave time to get the shots.
Children are at risk
Data presented at the most recent FDA advisory panel on COVID-19 vaccines showed that in the last year infants under six months had the third highest rate of hospitalization. “From the beginning, the message has been that kids don’t get COVID, and then the message was, well kids get COVID, but it’s not serious,” says Elias Kass, a pediatrician in Seattle. “Then they waited so long on the initial vaccines that by the time kids could get vaccinated, the majority of them had been infected.”
A closer look at the data from the CDC also reveals that from January 2022 to January 2023 children aged 6 to 23 months were more likely to be hospitalized than all other vaccine eligible pediatric age groups.
“We sort of forced an entire generation of kids to be infected with a novel virus and just don't give a shit, like nobody cares about kids,” Kass says. In some cases, COVID has wreaked havoc with the immune systems of very young children at his practice, making them vulnerable to other illnesses, he said. “And now we have kids that have had COVID two or three times, and we don’t know what is going to happen to them.”
Jumping through hurdles
Children under five were the last group to have an emergency use authorization (EUA) granted for the COVID-19 vaccine, a year and a half after adult vaccine approval. In June 2022, 30,000 sites were initially available for children across the country. Six months later, when boosters became available, there were only 5,000.
Currently, only 3.8% of children under two have completed a primary series, according to the CDC. An even more abysmal 0.2% under two have gotten a booster.
Ariadne Labs, a health center affiliated with Harvard, is trying to understand why these gaps exist. In conjunction with Boston Children’s Hospital, they have created a vaccine equity planner that maps the locations of vaccine deserts based on factors such as social vulnerability indexes and transportation access.
“People are having to travel farther because the sites are just few and far between,” says Benjy Renton, a research assistant at Ariadne.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. When the boosters first came out she expected her toddler could get it close to home, but her husband had to drive Charlee four hours roundtrip.
This experience hasn’t been uncommon, especially in rural parts of the U.S. If parents wanted vaccines for their young children shortly after approval, they faced the prospect of loading babies and toddlers, famous for their calm demeanor, into cars for lengthy rides. The situation continues today. Mrs. Smith*, a grant writer and non-profit advisor who lives in Idaho, is still unable to get her child the bivalent booster because a two-hour one-way drive in winter weather isn’t possible.
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited.
Protect Their Future (PTF), a grassroots organization focusing on advocacy for the health care of children, hears from parents several times a week who are having trouble finding vaccines. The vaccine rollout “has been a total mess,” says Tamara Lea Spira, co-founder of PTF “It’s been very hard for people to access vaccines for children, particularly those under three.”
Seventeen states have passed laws that give pharmacists authority to vaccinate as young as six months. Under federal law, the minimum age in other states is three. Even in the states that allow vaccination of toddlers, each pharmacy chain varies. Some require prescriptions.
It takes time to make phone calls to confirm availability and book appointments online. “So it means that the parents who are getting their children vaccinated are those who are even more motivated and with the time and the resources to understand whether and how their kids can get vaccinated,” says Tiffany Green, an associate professor in population health sciences at the University of Wisconsin at Madison.
Green adds, “And then we have the contraction of vaccine availability in terms of sites…who is most likely to be affected? It's the usual suspects, children of color, disabled children, low-income children.”
It can be more difficult for low wage earners to take time off, which poses challenges especially in a number of rural counties across the country, where weekend hours for getting the shots may be limited. In Bibb County, Ala., vaccinations take place only on Wednesdays from 1:45 to 3:00 pm.
“People who are focused on putting food on the table or stressed about having enough money to pay rent aren't going to prioritize getting vaccinated that day,” says Julia Raifman, assistant professor of health law, policy and management at Boston University. She created the COVID-19 U.S. State Policy Database, which tracks state health and economic policies related to the pandemic.
Most states in the U.S. lack paid sick leave policies, and the average paid sick days with private employers is about one week. Green says, “I think COVID should have been a wake-up call that this is necessary.”
Maskless waiting rooms
For her son, Holmes spent hours making phone calls but could uncover no clear answers. No one could estimate an arrival date for the booster. “It disappoints me greatly that the process for locating COVID-19 vaccinations for young children requires so much legwork in terms of time and resources,” she says.
In January, she found a pharmacy 30 minutes away that could vaccinate Theo. With her son being too young to mask, she waited in the car with him as long as possible to avoid a busy, maskless waiting room.
Kids under two, such as Theo, are advised not to wear masks, which make it too hard for them to breathe. With masking policies a rarity these days, waiting rooms for vaccines present another barrier to access. Even in healthcare settings, current CDC guidance only requires masking during high transmission or when treating COVID positive patients directly.
“This is a group that is really left behind,” says Raifman. “They cannot wear masks themselves. They really depend on others around them wearing masks. There's not even one train car they can go on if their parents need to take public transportation… and not risk COVID transmission.”
Yet another challenge is presented for those who don’t speak English or Spanish. According to Translators without Borders, 65 million people in America speak a language other than English. Most state departments of health have a COVID-19 web page that redirects to the federal vaccines.gov in English, with an option to translate to Spanish only.
The main avenue for accessing information on vaccines relies on an internet connection, but 22 percent of rural Americans lack broadband access. “People who lack digital access, or don’t speak English…or know how to navigate or work with computers are unable to use that service and then don’t have access to the vaccines because they just don’t know how to get to them,” Jirmanus, an affiliate of the FXB Center for Health and Human Rights at Harvard and a member of The People’s CDC explains. She sees this issue frequently when working with immigrant communities in Massachusetts. “You really have to meet people where they’re at, and that means physically where they’re at.”
Equitable solutions
Grassroots and advocacy organizations like PTF have been filling a lot of the holes left by spotty federal policy. “In many ways this collective care has been as important as our gains to access the vaccine itself,” says Spira, the PTF co-founder.
PTF facilitates peer-to-peer networks of parents that offer support to each other. At least one parent in the group has crowdsourced information on locations that are providing vaccines for the very young and created a spreadsheet displaying vaccine locations. “It is incredible to me still that this vacuum of information and support exists, and it took a totally grassroots and volunteer effort of parents and physicians to try and respond to this need.” says Spira.
Kass, who is also affiliated with PTF, has been vaccinating any child who comes to his independent practice, regardless of whether they’re one of his patients or have insurance. “I think putting everything on retail pharmacies is not appropriate. By the time the kids' vaccines were released, all of our mass vaccination sites had been taken down.” A big way to help parents and pediatricians would be to allow mixing and matching. Any child who has had the full Pfizer series has had to forgo a bivalent booster.
“I think getting those first two or three doses into kids should still be a priority, and I don’t want to lose sight of all that,” states Renton, the researcher at Ariadne Labs. Through the vaccine equity planner, he has been trying to see if there are places where mobile clinics can go to improve access. Renton continues to work with local and state planners to aid in vaccine planning. “I think any way we can make that process a lot easier…will go a long way into building vaccine confidence and getting people vaccinated,” Renton says.
Michelle Baltes-Breitwisch, a pharmacist, and her two-year-old daughter, Charlee, live in Iowa. Her husband had to drive four hours roundtrip to get the boosters for Charlee.
Michelle Baltes-Breitwisch
Other changes need to come from the CDC. Even though the CDC “has this historic reputation and a mission of valuing equity and promoting health,” Jirmanus says, “they’re really failing. The emphasis on personal responsibility is leaving a lot of people behind.” She believes another avenue for more equitable access is creating legislation for upgraded ventilation in indoor public spaces.
Given the gaps in state policies, federal leadership matters, Raifman says. With the FDA leaning toward a yearly COVID vaccine, an equity lens from the CDC will be even more critical. “We can have data driven approaches to using evidence based policies like mask policies, when and where they're most important,” she says. Raifman wants to see a sustainable system of vaccine delivery across the country complemented with a surge preparedness plan.
With the public health emergency ending and vaccines going to the private market sometime in 2023, it seems unlikely that vaccine access is going to improve. Now more than ever, ”We need to be able to extend to people the choice of not being infected with COVID,” Jirmanus says.
*Some names were changed for privacy reasons.
Amber Freed and Maxwell near their home in Denver, Colorado.
Getting the diagnosis took months of painful, invasive procedures, as well as fighting with the health insurance to get the genetic testing approved. Finally, in June 2018, doctors at the Children's Hospital Colorado gave the Freeds their son's diagnosis—a genetic mutation so rare it didn't even have a name, just a bunch of letters jammed together into a word SLC6A1—same as the name of the mutated gene. The mutation, with only 40 cases known worldwide at the time, caused developmental disabilities, movement and speech disorders, and a debilitating form of epilepsy.
The doctors didn't know much about the disorder, but they said that Maxwell would also regress in his development when he turned three or four. They couldn't tell how long he would live. "Hopefully you would become an expert and educate us about it," they said, as they gave Freed a five-page paper on the SLC6A1 and told her to start calling scientists if she wanted to help her son in any way. When she Googled the name, nothing came up. She felt horrified. "Our disease was too rare to care."
Freed's husband, a 6'2'' college football player broke down in sobs and she realized that if anything could be done to help Maxwell, she'd have be the one to do it. "I understood that I had to fight like a mother," she says. "And a determined mother can do a lot of things."
The Freed family.
Courtesy Amber Freed
She quit her job as an equity analyst the day of the diagnosis and became a full-time SLC6A1 citizen scientist looking for researchers studying mutations of this gene. In the wee hours of the morning, she called scientists in Europe. As the day progressed, she called researchers on the East Coast, followed by the West in the afternoon. In the evening, she switched to Asia and Australia. She asked them the same question. "Can you help explain my gene and how do we fix it?"
Scientists need money to do research, so Freed launched Milestones for Maxwell fundraising campaign, and a SLC6A1 Connect patient advocacy nonprofit, dedicated to improving the lives of children and families battling this rare condition. And then it became clear that the mutation wasn't as rare as it seemed. As other parents began to discover her nonprofit, the number of known cases rose from 40 to 100, and later to 400, Freed says. "The disease is only rare until it messes with the wrong mother."
It took one mother to find another to start looking into what's happening inside Maxwell's brain. Freed came across Jeanne Paz, a Gladstone Institutes researcher who studies epilepsy with particular interest in absence or silent seizures—those that don't manifest by convulsions, but rather make patients absently stare into space—and that's one type of seizures Maxwell has. "It's like a brief period of silence in the brain during which the person doesn't pay attention to what's happening, and as soon as they come out of the seizure they are back to life," Paz explains. "It's like a pause button on consciousness." She was working to understand the underlying biology.
To understand how seizures begin, spread and stop, Paz uses optogenetics in mice. From words "genetic" and "optikós," which means visible in Greek, the optogenetics technique involves two steps. First, scientists introduce a light-sensitive gene into a specific brain cell type—for example into excitatory neurons that release glutamate, a neurotransmitter, which activates other cells in the brain. Then they implant a very thin optical fiber into the brain area where they forged these light-sensitive neurons. As they shine the light through the optical fiber, researchers can make excitatory neurons to release glutamate—or instead tell them to stop being active and "shut up". The ability to control what these neurons of interest do, quite literally sheds light onto where seizures start, how they propagate and what cells are involved in stopping them.
"Let's say a seizure started and we shine the light that reduces the activity of specific neurons," Paz explains. "If that stops the seizure, we know that activating those cells was necessary to maintain the seizure." Likewise, shutting down their activity will make the seizure stop.
Freed reached out to Paz in 2019 and the two women had an instant connection. They were both passionate about brain and seizures research, even if for different reasons. Freed asked Paz if she would study her son's seizures and Paz agreed.
To do that, Paz needed mice that carried the SLC6A1 mutation, so Freed found a company in China that created them to specs. The company replaced a mouse SLC6A1 gene with a human mutated one and shipped them over to Paz's lab. "We call them Maxwell mice," Paz says, "and we are now implanting electrodes into them to see which brain regions generate seizures." That would help them understand what goes wrong and what brain cells are malfunctioning in the SLC6A1 mice—and help scientists better understand what might cause seizures in children.
Bred to carry SLC6A1 mutation, these "Maxwell mice" will help better understand this debilitating genetic disease. (These mice are from Vanderbilt University, where researchers are also studying SLC6A1.)
Courtesy Amber Freed
This information—along with other research Amber is funding in other institutions—will inform the development of a novel genetic treatment, in which scientists would deploy a harmless virus to deliver a healthy, working copy of the SLC6A1 gene into the mice brains. They would likely deliver the therapeutic via a spinal tap infusion, and if it works and doesn't produce side effects in mice, the human trials will follow.
In the meantime, Freed is raising money to fund other research of various stop-gap measures. On April 22, 2021, she updated her Milestone for Maxwell page with a post that her nonprofit is funding yet another effort. It is a trial at Weill Cornell Medicine in New York City, in which doctors will use an already FDA-approved drug, which was recently repurposed for the SLC6A1 condition to treat epilepsy in these children. "It will buy us time," Freed says—while the gene therapy effort progresses.
Freed is determined to beat SLC6A1 before it beats down her family. She hopes to put an end to this disease—and similar genetic diseases—once and for all. Her goal is not only to have scientists create a remedy, but also to add the mutation to a newborn screening panel. That way, children born with this condition in the future would receive gene therapy before they even leave the hospital.
"I don't want there to be another Maxwell Freed," she says, "and that's why I am fighting like a mother." The gene therapy trial still might be a few years away, but the Weill Cornell one aims to launch very soon—possibly around Mother's Day. This is yet another milestone for Maxwell, another baby step forward—and the best gift a mother can get.