COVID-19 Vaccines for Children: Aspiring Towards a Safer World

Children have traditionally been the primary recipient of vaccines. Childhood constitutes the most vulnerable period for falling seriously ill with vaccine-preventable illnesses, and hence this is the period when protection is most needed. Their naïve immune systems are quick to react to antigens presented to them as vaccines, often resulting in long-term immunity against disease. Children can be walking petri dishes and are capable of carrying pathogens and transmitting infection to others, thus protecting them with vaccines may help reduce transmission within the community.

The glimmer of hope for a COVID-19 vaccine that was nursed guardedly in the early part of 2020 has erupted into a glorious blaze of promise as the global scientific community has produced over a hundred vaccine candidates and several vaccines approved for emergency use among vulnerable people. Phase III clinical trials indicate that these vaccines are over 90% efficacious with clear safety profiles so far. Uncommon speed, unprecedented global collaboration, and unequivocal public and private sector support have marked the development of these vaccines. The first group of people who are being vaccinated are healthcare workers, the elderly, and those with serious underlying conditions.

While there are several looming questions about the nature of COVID-19 vaccine deployment, other questions that come to the fore are about children and youth: when will they be considered for vaccination? Let us consider the broad reasons for including children among COVID-19 vaccine recipients in the near-term.

Five reasons why children should get a COVID-19 vaccine

First, children under the age of 18 years form a large proportion of the population (24% in the US and 32% globally). Ensuring protection to a group that constitutes a quarter of the total population seems essential as we progress towards control of the pandemic.

Second, it is well known that children can efficiently transmit SARS-CoV-2, the virus that causes COVID-19. The Centers for Disease Control and Prevention (CDC) has shown through contact tracing data that infants and children can transmit the virus to their household contacts. This is a familiar phenomenon seen with other dangerous pathogens such as pneumococcus. In countries where there was good coverage of the pneumococcal conjugate vaccine among children, adults who were unimmunized appeared to be protected and showed lower rates of pneumonia. These observations suggest that vaccinating children can reduce the overall burden of SARS-CoV-2 infection.

Third, while children are not the ones to suffer most from COVID-19, they can fall seriously ill. In November 2020, the American Academy of Pediatrics reported that over one million children in the US were infected with SARS-CoV-2, indicating that over one in ten cases is a child. Although overall mortality among children has been low, hundreds have died and many thousands have been seriously ill with an inflammatory condition called Multisystem Inflammatory Syndrome in Children (MIS-C).

Fourth, the indirect effects of COVID-19 on children have been devastating. Education is clearly suffering and 2020 is a lost year for a generation of children. Analysis in county public schools indicated an increase in the proportion of children with failing grades during the COVID-19 era of remote learning. Pediatric emergency department visits for mental health issues have been on the rise, with increases in anxiety and social isolation seen among children and families. A COVID-19 vaccine for children would provide a safer educational environment and would support re-opening of schools for in-person learning and other co-curricular activities.

Fifth, the application of the ethical principle of distributive justice that expresses the ideal that benefits and burdens are distributed among society's members in a just manner, means that children should not be excluded from consideration for receiving COVID-19 vaccines, as noted in a letter by the president of the American Academy of Pediatrics to federal health officials. The observation that children appear to have lower risk of severe COVID-19 disease compared with adults should not result in their exclusion from vaccine clinical research.

Including children in COVID-19 vaccine clinical trials

Before we reach the point of planning for children to get COVID-19 vaccines, it is essential to include children in vaccine clinical trials right away to glean critical information on the safety and efficacy of these vaccines in children.

It is well known that children are not ‘little adults’ – their physical, metabolic, immunological, and psychological processes are different from those of adults. Younger children have more active immune responses to vaccines than adults that often translate to children having stronger reactions, such as higher fever and localized reactions. Thus, separate safety data in children must be meticulously collected and critically studied before recommendations can be made for deployment in children. Similarly, efficacy data are important to compile in different age categories given the differential immune responses in different ages. Initiating Phase 2 studies in children simultaneously with Phase 3 studies among adults to identify optimal pediatric doses would also increase the efficiency of conducting Phase 3 trials in children.

In July 2020, the FDA issued an emergency use authorization for remdesivir that included children although no pediatric data were available. While it may be argued that the inclusion is acceptable for drugs that work by interfering with SARS-CoV-2 replication, in the case of vaccines, there are additonal factors to consider. Hence it is imperative to include children in vaccine trials at the earliest possible time. The argument may be extended to state that, given adolescents’ physiologic similarity to adults and the advantage of gaining knowledge expeditiously, the inclusion of adolescents in adult trials may be justifiable. Including different age categories of children can make the clinical trial a lengthy process, called age de-escalation. These trials may start with older children initially and continue the step-down process by including younger age groups, all the while carefully monitoring safety and efficacy and often adjusting vaccine doses.

A few words of caution

A dollop of caution and realism will go a long way when keeping track of goals and activities for the best and most successful outcomes.

A peculiar immunological phenomenon to watch out for is called antibody-dependent enhancement (ADE), in which antibodies to SARS-CoV-2 elicited from a vaccine may result in worse disease. Previous experience from other vaccine trials of respiratory syncytial virus (RSV) and dengue virus vaccine have resulted in this outcome, resulting in heavy risks and failed vaccine trials. Thus, long-term monitoring of vaccine safety within trials and in the general population is critical to building a strong safety profile of the vaccine products that are to be used in children.

Running pediatric vaccine trials is more complicated compared to adult trials and an integrated and sustainable trials network geared towards pediatric approaches is necessary. Previously, approval of a product for pediatric use used to take approximately nine years after approval of a product for adult use. The barriers include operational, informational and ethical factors. A key gathering of stakeholders in November 2014 addressed the challenges in conducting clinical trials by establishing a pediatric clinical trials network. Such a network, run by dedicated personnel with expertise in conducting trials in children, would provide the infrastructure and rigor needed to improve the safety and efficacy of products for children, including vaccines.

Finally, an open channel of communication with the public with complete transparency of what is known and unknown is urgently needed to build vaccine confidence. Current and future trial enrollments should reflect the racial and ethnic diversity of the US and global populations, including children and pregnant women, and contribute to reducing inequities among societies.

The vaccine made by Pfizer/BioNTech is now being tested in children aged 12-17 years since October 2020. Similarly, Moderna initiated trials in children 12 years and above and will include approximately 3,000 children. AstraZeneca has also tested its vaccine in children in the UK and US, and has been one of the earliest to include young children. However, there is still much learning to be had and this is a rapidly evolving field that is being watched at close quarters by the entire world.

Children’s overall risk of COVID-19 is not insignificant. When the stage is reached where COVID-19 vaccines can be deployed among children, we would have truly reached a pinnacle of success, where a large proportion of the adults would have been vaccinated and sufficient vaccine doses would have been manufactured and ready for shipping to children. Understanding the impact of COVID-19 vaccines in children is the pathway towards making the world a safer place.