The conundrum of Covid vaccines for children, adolescents and youth

By Dr B. J. C. Perera

MBBS(Cey), DCH(Cey), DCH(Eng), MD(Paed), MRCP(UK), FRCP(Edin), FRCP(Lon), FRCPCH(UK), FSLCPaed, FCCP, Hony FRCPCH(UK), Hony. FCGP(SL).

Specialist Consultant Paediatrician and Honorary Senior Fellow, Postgraduate Institute of Medicine, University of Colombo, Sri Lanka.

There is a lot of interest as well as differences of opinion and even misinformation regarding many aspects of vaccination of children, and young people, against Covid-19. This has led to a considerable amount of anxiety in the minds of parents, and even the youth themselves, regarding the different facets of vaccinating these subjects against the coronavirus infection that is running riot, all over the world, including Sri Lanka. Against this background, it is also pertinent to point out that there is a very definite recent increase in the numbers of children who have tested positive for the coronavirus disease, especially in some of the developed countries with facilities available for large scale testing of the general population.

There is a considerable number of differing opinions expressed regarding the need to vaccinate these age groups of subjects. True enough, it is argued that children, and young people, are not as susceptible to major effects. However, there are documented cases, though quite rare, of children, and young people, getting the Multisystem Inflammatory Syndrome (MIS-C) complication of Covid-19. That particular problem could affect several body systems and organs. It is a somewhat delayed but a rather nasty complication which, if it is not properly and promptly treated, could even lead to death. Then, of course, there is the spectacle of ‘Long Covid’, where there are persistent symptoms, particularly of a respiratory nature, for quite some time, after apparent recovery from symptomatic Covid-19. There are some reports of persistent vague symptoms, even in those who were originally not sick with symptomatic disease. It is also noteworthy that there are reports of significant x-ray changes that have been detected in some completely asymptomatic positive cases. It must also be considered that the clinical picture of Covid-19, in children, seems to fluctuate considerably, over different time periods. There is no guarantee that there is no risk at all of the disease suddenly turning quite virulent and starting to produce marked and severe symptoms, even in children. This is particularly of relevance in view of the propensity for the coronavirus to undergo mutations, as it keeps on replicating.

Children rarely become severely ill from Covid-19. However, in the US, in August, 2021, the Delta variant has landed nearly 30,000 of them in hospital. According to the American Academy of Pediatrics, nearly 5.9 million Americans younger than 18, have been infected with the coronavirus. Of the roughly 500 Americans, under 18, who have died, about 125 were aged 5 to 11. “It really bothers me when people say kids don’t die of Covid”, said Dr. Grace Lee, an Associate Chief Medical Officer, at Stanford Children’s Health, who also leads a key Advisory Committee to the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. She also said “They die of Covid. It’s heart-breaking”. About one in six Americans infected, since the beginning of the pandemic, was under 18. But with the surge of the Delta variant, children accounted for as many as one in four infections in recent times, according to the American Academy of Pediatrics.

Then, of course, there is the problem of asymptomatic afflicted children carrying the virus around and spreading it, and, perhaps, much more importantly, the scenario of them taking it home and infecting susceptible adults and the elderly. With rather close gatherings during transport, to and from schools, and also in the classrooms themselves, the risks of these children contracting the virus is something quite real. There are some sporadic studies that indicate that there is some protection provided by the vaccines in actually preventing, to a certain degree, the exposed individuals from contracting the virus. This is, of course, is not 100% protection by any means, but is a rather minor but a positive reason for vaccination.

At this point in time, the only coronavirus vaccine that is universally authorised to be administered to children and, young people, over the age of 12, is the mRNA Pfizer – BioNTech Covid-19 (BNT162b2) vaccine, with the brand name “Comirnaty”. The European countries, and Australia, have been provided provisional authorisation for the use of the Moderna mRNA-1273 vaccine with the brand name “Spikevax” in those over 12 years of age. In several studies, the effectiveness of these vaccines, as well as their safety, have been established.

Yet for all that, there are some of the more recent reports of the occurrence of the extremely rare complications of myocarditis and pericarditis occurring, especially in adolescent and young males with all mRNA Covid-19 vaccines, particularly after the second dose of the vaccine, occurring typically within a few days after vaccination. Myocarditis is an inflammation of the heart muscle and pericarditis is an inflammation of the lining that surrounds the heart. Available data suggest that the immediate course of myocarditis and pericarditis, following vaccination, is generally mild and responds to conservative treatment. So far, major problems, with long-term heart functions, have been see in these cases and follow-up is ongoing to determine possible long-term outcomes. All young recipients of mRNA vaccines should be instructed to report for medical attention if they develop symptoms, indicative of myocarditis or pericarditis such as new onset and persisting chest pain, shortness of breath, or palpitations, following vaccination against Covid-19. It has to be reiterated that these complications are extremely rare. In the USA there have been no deaths reported in young people developing myocarditis, following mRNA Covid-19 vaccines.

In a most reassuring publication, released on 22nd October 2021, hot off the oven so to speak, both BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca) vaccines offered substantial protection against death from coronavirus disease 2019 (COVID-19) caused by the B.1.617.2 (Delta) variant, according to a study published in The New England Journal of Medicine. Meanwhile, another study, also published recently in The New England Journal of Medicine, suggests that the BNT162b2 (Pfizer-BioNTech) vaccine was highly effective against both documented infection and symptomatic COVID-19 with the Delta variant among adolescents, between the ages of 12 and 18 years. The latest information available to us seem to confirm the benefits of Covid-19 vaccinations in adolescents and young people.

The most recent development, from the standpoint of Covid-19 vaccinations for children, is the application due to be made by Pfizer to the Food and Drugs Administration (FDA) of USA for authorisation for usage of its Covid-19 vaccine for children, 5 to 11 years of age. In a highly anticipated announcement, Pfizer has said that a Phase 2/3 trial showed its Covid-19 vaccine was safe and generated a “robust” antibody response in children, aged 5 to 11.

These are the first such results released for this age group for a USA Covid-19 vaccine.

The trial included 2,268 participants, ages 5 to 11, and used a two-dose regimen of the vaccine, administered 21 days apart. This trial used a 10-microgram dose, which is one third of the 30-microgram dose that has been used for those 12 and older. Pfizer has said that the 10-microgram dose was carefully selected as the preferred dose for safety, tolerability and immunogenicity in children 5 to 11 years of age.

Participants’ immune responses were measured by looking at neutralising antibody levels in their blood and comparing those levels to a control group of 16 to 25-year-olds who were given a two-dose regimen with the larger 30-microgram dose. Pfizer has said the levels compared well with older people who received the larger dose, demonstrating a “strong immune response in this cohort of children, one month after the second dose”. They have further stated that the vaccine was well tolerated, with side effects generally comparable to those observed in participants, 16 to 25 years of age.

However, it is a matter for some concern that this data has not yet been peer-reviewed or published in a reputed medical journal. Pfizer has said that it plans to submit the data directly to the US Food and Drug Administration for emergency use authorisation. Apparently, the FDA officials have said that once the data is submitted, the agency could authorise the vaccine for younger children, in a matter of weeks.

Albert Bourla, Chairman and Chief Executive Officer of Pfizer, said in a statement “Since July 2021, pediatric cases of COVID-19 have risen by about 240 percent in the USA, underscoring the public health need for vaccination. These trial results provide a strong foundation for seeking authorisation of our vaccine for children 5 to 11 years old, and we plan to submit them to the FDA and other regulators with urgency”. Pfizer also said that it is expecting trial data for children as young as six months as soon as the fourth quarter of this year.

In addition, Moderna Incorporated plans for double enrolment in a trial of its Covid-19 vaccine in children under age 12, following a request from U.S. regulators to collect additional safety data. Moderna’s study will enrol an estimated 13,275 participants aged 6 months up to 12 years old, according to a listing on the clinicaltrials.gov website. In a post from late July, the Cambridge, Massachusetts-based company said it would seek to enrol about 7,000.

As things stand now, the scientific information regarding the feasibility of administering the Covid-19 vaccination to very young children is, at best, in a state of flux at the present time. We need to await the results of several on-going Clinical Trials. The Sri Lanka College of Paediatricians will keep a close watch on the developments and would take all necessary steps to advise the authorities on the best course of action, when more tangible evidence from Clinical Trials emerge in the future.

The gut-feeling of a lot of authorities involved in child healthcare is that it would be possible to vaccinate even young children against Covid-19 in the not-too-distant future. The benefits due to be gained seemingly appear to be that much more important and would override the very rare undesirable effects in our quest towards victory over this pandemic that has brought the entire world to its knees.