Vaccine Development, Rollout Underlines Priorities in Public Health Decision-Making

This article is part of Contagion’s one-year COVID-19 series, which will run in 3 parts, March 17-19. You can share your thoughts, questions, reflections, and concerns from this last year in the pandemic through our channels on Facebook, Twitter, and LinkedIn.

A text message from the school district comes across a mom’s phone: “An individual at the school has tested positive for COVID-19.” The message goes on to say they have done contact tracing and what the results were. The message does not identify who was infected nor even say if they were a student, teacher, or administrator. In fact, there is no information shared on the person’s condition.

Follow-up questions, of which there are many, are directed to the school nurse. The nature of the text message is business-like, impersonal. For the schools, this is simply a way to keep families informed about new cases. For families, this can be unnerving. And when they begin to get this same message multiple times over the course of a week, it begins to shake their faith in whether students should be in school at all.

There’s hope those text message scenarios may begin to fade away in the fall semester. Earlier this week, Moderna announced it was beginning a phase 2/3 study with its COVID-19 vaccine in children ages 6 months to 12 years old.

In totality, they are looking to enroll 6750 healthy pediatric participants. The trial is going to be done in 2 parts. For the first part—a dose-escalation, age de-escalation phase—children between the ages of 2 and 12 will receive 1 of 2 dose levels (50 μg or 100 μg) of the vaccine, and each participant aged 6 months to less than 2 years may receive one of three dose levels (25 μg, 50 μg and 100 μg).

After the first portion of the study, an interim analysis will then be conducted in which investigators will determine the dosage for the second portion of the trial. This will also include a placebo-controlled expansion. Pediatric vaccine trials are finally beginning.

As the prolific COVID-19 vaccine development and distribution plan turns toward children, it’s critical to remember the pandemic intricacies at play in its youngest patients.

A Glimpse of the Pediatric Population

As of March 11, over 3.28 million American children had been diagnosed with COVID-19, according to a report from the American Academy of Pediatrics (AAP) and the Children’s Hospital Association. This information comes from 43 US states, New York City, Puerto Rico, and Guam reporting their cases.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the AAP wrote on its site. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

Indeed there is a lot at stake with children for not only containing the virus and the physiological aspects, but also kids’ long-term well-being. “We know the indirect effects of the pandemic are huge, both in terms of not being able to go to school and not having social interactions and all sorts of mental health problems that have been emerging,” Seema Shah, JD, associate professor, Founder’s Board Professor of Medical Ethics, Department of Pediatrics, Northwestern University Feinberg School of Medicine, and associate director of Research Ethics, Ann & Robert H. Lurie Children’s Hospital, said.

Shah has been involved in looking at the ethics of trials including a potential Zika virus trial, so she understands the nuances of the topic and the tough questions that need to be asked before proceeding in prospective trials.

At the Ann & Robert H. Lurie Children’s Hospital of Chicago, they have seen a fair amount of children diagnosed with COVID-19, acknowledged Bill Muller, MD, PhD associate professor, Pediatrics, Northwestern University Feinberg School of Medicine and interim associate chief research officer for Clinical Trials, Lurie Children’s Hospital. All patients who are admitted to the hospital are screened for COVID-19 as well as those undergoing procedures.

In pediatrics, Muller says this patient population has run the full gamut of mild to severe disease. He says while approximately 50% of children diagnosed are asymptomatic and a majority of them get discovered in the outpatient setting, he is also quick to point out that there are other patients who have been hospitalized and have been put on a ventilator.

“COVID has killed as many children as the worst flu season,” Muller said. And, according to the aforementioned AAP report, 266 children have died from COVID-19.

And this does not begin to address the lingering effects of COVID-19 or unique conditions related to the virus in children. “Fewer children have been sick with COVID-19 compared to adults,” the US Centers for Disease Control and Prevention (CDC) wrote on its website. “However, children with certain underlying medical conditions and infants (less than 1 year old) might be at increased risk for severe illness from COVID-19. Some children have developed a rare but serious disease that is linked to COVID-19 called multisystem inflammatory syndrome (MIS-C).”

A Missed Opportunity?

Up until Moderna’s announcement this week, vaccine studies have been focused on the older kids. With the pandemic now a year old, was it an oversight to not study the pediatric population until now?

Muller doesn’t believe it was an oversight, especially as the people most affected by the virus were the senior population and people with existing health conditions.

“I think the urgency to create a vaccine that was approvable in adults first made sense,” Muller said. “Typically, when drugs are developed, and vaccines fit into this category as well, studies are initially done in adults before they are extended into children.”

However, he does acknowledge that the pediatric trials could have started sooner. He points to Pfizer-BioNTech developing an additional arm late in their trials for younger participants down to the age of 16 that allowed them to receive an Emergency Use Authorization (EUA) for that age and older.

During the Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting to discuss the Pfizer-BioNTech vaccine in December, there was an open debate among committee members on the appropriate age for the vaccine. Eventually the committee voted to nonetheless recommend the vaccine for everyone 16 and older.

Muller said there were 2 primary reasons for extending vaccinations down to 16 year-olds: the vaccines’ safety profile, and greater community safety. “There were no safety concerns about the vaccine; they seemed to do well when they got it—and these were very large studies,” Muller said. “There is a little bit of a misconception sometimes that the speed made the studies smaller, but it actually didn’t.”

Secondarily, teens are often working on the frontlines where they are engaging with the public acknowledges Muller. And the concern is that while most kids may be asymptomatic, they could bring it home to other family members.

In looking at younger populations who are 12 and under, more study considerations are needed. Muller said study designers need to consider dosage amounts, what measures of antibody markers to study, and if they need a placebo arm for the trial.

“There are logistical hurdles to do it, but it can be done,” Muller said.

Getting Kids Back to School

In order to get all kids back to the classroom, and feel a level of public safety, a vaccine strategy must be enacted for the pediatric population. And to be clear, if the overarching goal continues to be achieving herd immunity, kids need to be vaccinated.

“I absolutely do think trying to develop vaccines for children is really important in this pandemic,” Shah said.

Biden Administration chief medical advisor Anthony Fauci, MD, has said it will take 75-85% of the population to get vaccinated to achieve herd immunity. Therefore, the potential to reach this goal is impossible if children are not vaccinated.

“The under 18 population is about 20% of the population, and I don’t think you are going to get 100% of adults to get vaccinated, so to get to 80% to get to herd immunity, you are going to need to have some kids get vaccinated,” Muller stated.

This will take a combination of biopharmaceutical companies continuing to ramp up pediatric studies, a willingness of families to get their children vaccinated, and public health policy.

Pediatric studies, Muller explains, will go a long way in not only informing how to vaccinate children but will serve as a source of public trust. “We need to send the right message to the general public that this has been done the right way,” Muller said. “We have made all the appropriate steps to ensure when we do extend vaccines to other populations including children and pregnant women, that we have done so in a safe matter.”

Shah concurred on gaining the public’s trust. “It is really critical to be thinking of trust,” Shah said. “Research is one of those things where we are asking some people to take on risks for the benefit of others in society.”

Muller and others in the medical community are understanding of asking families to take on these potential risks, and he said there has been a great willingness on the part of the public to help.

“People have been incredibly enthusiastic about contributing to our understanding of this disease,” Muller said. “Everyone understands how important it is for scientists and clinicians to get more information on COVID. I think that has helped us with the drug studies in pediatrics, and that will extend to the vaccine studies into the youngest age groups.”

While the vaccination studies and rollout continue to evolve, the experimentation that is going on now will inform how they are carried out in the future. Daniel Hausman, PhD, research professor in the Center for Population–Level Bioethics, Rutgers University, as many others, believes there will be future viruses we have to contend with, and everything from testing to vaccine/therapy development to rollout will get better based off our current experience.

“There is a lot of learning by doing…and I think we will get better at it,” Hausman said of the ramp-up of vaccine administration.

And in the case of looking at how the federal and state governments can lend its assistance by creating public health policy it can be seen as a universal good according to Hausman. “Even in people who are very reserved about government involvement in health care can quite easily appreciate its importance here.”

As the Biden administration has worked to ramp-up mass vaccinations across the country, some states are doing their part to put rules in place to speed up the pace in the pediatric population. In recent days, both Alaska and Mississippi became the first states to open up vaccine eligibility to include anyone aged 16 years or older.

Working Towards Normalcy

Many believe that the US is aiming for an atmosphere of normalcy later this year—this includes being able to get out in public and for all kids to be back in school. The CDC, for example, created guidance to get children back to school for in-person learning, including revising its recommendation for students sitting in school from 6 feet to 3 feet apart.

In addition, The Infectious Diseases Society of America (IDSA) hosted a press briefing this week, providing information and feedback on getting children back in the classroom.

And as pediatric COVID-19 vaccine trials ramp-up, and data is expected in the next few months, a case could be made that vaccines will be available later this year.

“My hope is that it would be the fall,” Muller said of a potential timeline for pediatric vaccinations to begin. He thinks vaccination authorizations could reach age 12 by the end of summer. “That would be important to opening schools in those age groups, and reassuring teachers that their risk is less…decreasing that risk by vaccinating the children is an important complement to this.”

And once the US begins vaccinations in the pediatric population, maybe some semblance of life before March 2020 may take hold again, but with the knowledge of the fragility of life and how it can quickly turn from hope to despair.

Here’s to the former being the reality the entire population can share again.