COVID-19: A look at the data supporting COVID vaccination of 5–11-year-old children (8 November 2021)
On 29 October 2021, the U.S. Food and Drug Administration (FDA) granted emergency use authorization (EUA) for use of the Pfizer-BioNTech COVID-19 vaccine in children 5 through 11 years of age. In their news release, the FDA stated that the authorization was based on a “thorough and transparent evaluation of the data that included input from independent advisory committee experts who overwhelmingly voted in favor of making the vaccine available to children in this age group” (1). Subsequently, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommended the vaccine for children ages 5 through 11; and that indication was endorsed by CDC Director Rochelle P. Walensky, M.D., M.P.H. on 2 November, expanding access of the vaccine to 28 million children in the U.S. (2). Nonetheless, according to an October Kaiser Family Foundation poll, 35% of parents said they either definitely wouldn’t vaccinate or wouldn’t unless required, and some 38% said they would take a “wait and see” approach (3). The commonest reason cited for vaccine hesitancy was vaccine safety, with more than seven in ten parents saying they were “very” or “somewhat” concerned that not enough is known about the long-term effects of the COVID-19 vaccine in children (76%) or their child might experience serious side effects (such as infertility) from the COVID-19 vaccine (71%). Notably, lower income parents were also more likely to be concerned about taking time off of work to get their children vaccinated. Here, I take a brief look at the data informing the FDA and CDC endorsements of the Pfizer-BioNTech COVID-19 vaccine for use in children 5 through 11 years of age, as well as the relative risks of vaccination versus non-vaccination.
On 20 September 2021, Pfizer Inc. and BioNTech announced results from a Phase 2/3 clinical trial which had enrolled 4,500 children 6 months to 11 years of age, including 2,268 children who were 5 to 11 years of age (4). The children had no prior evidence of SARS-CoV-2 infection and received two doses of vaccine. The children in the 5–11-year cohort received two 10 microgram (mcg) doses (which is one- third of the adolescent and adult doses) approximately 21 days apart. The study investigators then measured neutralizing antibody titers one month after the second dose and found the geometric mean titer (GMT) to be 1,197.6 (95% confidence interval [CI, 1106.1, 1296.6]) suggestive of a strong immune response. This was comparable to the GMT of 1146.5 (95% CI: 1045.5, 1257.2) from participants ages 16 to 25 years old, who had been administered a two-dose regimen of 30 mcg and were used as the control group in this study. Additionally, the study investigators stated the vaccine was 90.7% effective in preventing symptomatic COVID-19. On the matter of safety, the commonest reactions were mild or moderate and included pain at the injection site, fatigue, and headache. No serious adverse events were reported from this trial. Although the entirety of the data are not yet publicly available, Pfizer and BioNTech do plan on submitting the results of the full Phase 3 trial for scientific peer-reviewed publication. Of note, there have been a small number of cases of myocarditis (inflammation of heart muscle) and pericarditis (inflammation of the fibrous membrane surrounding the heart) reported among adolescents after receipt of mRNA vaccines, raising concern for the possibility of the same complication among 5- to 11-year-old vaccinees. In one study of 2.5 million people 16 years of age or older who received the Pfizer–BioNTech BNT162b2 mRNA vaccine, 54 cases were documented, giving an estimated incidence of 2.13 cases per 100,000 persons who had received at least one dose of vaccine (95% confidence interval [CI], 1.56 to 2.70). Most cases occurred in male patients 16 to 29 years of age, with 76% of cases described as mild and 22% as intermediate (5). No cases of myocarditis or pericarditis were reported in Pfizer’s clinical trial of 5- to 11-year-old children; although admittedly, the incidence may be too low to have occurred in a trial of that size. That notwithstanding, the American Academy of Pediatrics updated its COVID-19 vaccination guidelines to “strongly recommend” the vaccine for children ages 5 to 11 years, regardless of prior COVID-19 infection, who do not have a contraindication to the vaccine (6). Of course, long term effects of the vaccines can only be excluded after sufficient time has passed. However, the vaccines appear to be as safe now as they were touted to be when they were first released a year ago; and on the matter of infertility: that concern seems to be unsupported, something about which I have written previously (7).
Because no vaccine is entirely risk-free, the decision whether or not to get one’s children vaccinated against COVID-19 should be made after weighing the relative risks of vaccination versus non-vaccination. With this in mind, what is the current risk posed by COVID-19 to children? According to the AAP, as of 28 October, nearly 6.4 million children have tested positive for COVID-19 since the onset of the pandemic (8). The pandemic peak for children was nearly 252,000 child cases added the week of 2 September followed by eight consecutive weekly decreases including 101,000 child COVID-19 cases this past week. Since the start of the pandemic, children represented 16.6% of total cumulated cases but more recently account for 24.2% of reported weekly COVID-19 cases. Among 49 states reporting data, children presently account for 1.7%-4.2% of hospitalizations and 0.1%-2.0% of child COVID-19 cases result in hospitalization. Presently, 0.00%-0.03% of all child COVID-19 cases result in death and between 1 January 2020 and 16 October 2021, there have been 94 COVID-19-related deaths reported among U.S. children age 5 to 11 years (9). Thus, it appears that at this time, severe illness or death due to COVID-19 remains uncommon among children. One complication of COVID-19 infection of children that does bear mentioning is multisystem inflammatory syndrome in children (MIS-C). Although rare (4,196 reported cases as of June 2021), MIS-C is a serious and potentially fatal (37 documented deaths) systemic inflammatory condition with an average onset 2 to 6 weeks after infection (10).
Although severe illness or death among children from COVID-19 remains uncommon, there are other considerations when deliberating the pros and cons of vaccination including the lingering effects of COVID-19, lost school days, and the extent to which infected children transmit the SARS-CoV-2 virus to others. With respect to the latter, several population and school-based studies suggest that children may be less likely than adults to become infected and to infect others (11). However, among children, this risk may be inversely correlated with age (12). Another consideration is the impact of COVID-19 on school attendance. According to a survey of 790 K-12 educators conducted by Education Week, student absences have doubled during the pandemic, climbing from 5% on a typical day before the pandemic to 10 percent now (13). Absenteeism appears to correlate with age, with high schoolers slightly more likely to be absent (13% on a typical day) than middle (11 %) or elementary schoolers (9%). Additionally, any deliberation about withholding COVID-19 vaccination from children should include a discussion of the potential lingering effects of infection. It is currently estimated that more than a third, and perhaps almost all, adult patients with SARS-CoV-2 infection may be at risk for lingering sequelae from their infection (14); and in one national survey in the United Kingdom, nearly one in seven adults still had symptoms at twelve weeks (15). Similarly, “Post-COVID” or “Long-COVID” syndrome is increasingly recognized in children as well. In one study of 129 children in Italy who were diagnosed with COVID-19 between March and November 2020 at the Gemelli University Hospital in Rome, more than half of children aged 6 to 16 years-old who contracted the virus had at least one symptom lasting more than 120 days, with 42.6% having impaired ability to perform the activities of daily living (16). Similarly, in the United Kingdom, it has been estimated that 12.9% of children aged 2 to 11 years, and 14.5% of children aged 12 to 16 years, still have symptoms five weeks after they become infected (17).
Thus, on the matter of whether or not to vaccinate children ages 5 to 11 years against COVID-19, current data suggest that while the risk of serious illness or death from infection is low, the risk posed by the vaccines is lower. Moreover, other sequelae of COVID-19 infection such as lost school days and the potential for “post-COVID” or “long-COVID” syndrome tip the scale in favor of vaccination. Lastly, it is worth pointing out that as more adults are vaccinated against COVID-19, unvaccinated children will likely play an increasingly prominent role in transmitting the virus, making immunity in this demographic a critical step in curbing the pandemic.
As with my prior COVID-19-themed posts, my intention here is not to politicize, sensationalize, or trivialize the pandemic, but only to provide information and thoughtful commentary.
Until my next update — regards.
Michael Zapor, MD, PhD, CTropMed, FACP, FIDSA
(8 November 2021)
References
1. https://www.fda.gov/news-events/press-announcements/fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use-children-5-through-11-years-age (Accessed 5 November 2021)
2. https://www.cdc.gov/media/releases/2021/s1102-PediatricCOVID-19Vaccine.html (Accessed 5 November 2021)
3. https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-october-2021/ (Accessed 5 November 2021)
4. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-positive-topline-results (Accessed 5 November 2021)
5. 10. https://www.nejm.org/doi/full/10.1056/NEJMoa2109730?query=recirc_curatedRelated_article
6. https://www.aap.org/en/news-room/news-releases/aap/2021/american-academy-of-pediatrics-applauds-cdc-approval-of-safe-effective-covid-19-vaccine-for-children-ages-5-11/ (Accessed 5 November 2021)
8. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/ (Accessed 5 November 2021)
9. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-11-2-3/03-COVID-Jefferson-508.pdf (Accessed 5 November 2021)
10. https://www.yalemedicine.org/news/multisystem-inflammatory-syndrome-in-children-misc-covid-kids
11. 12. Paul LA, Daneman N, Schwartz KL, et al. Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection. JAMA Pediatr. 2021;175(11):1151–1158. doi:10.1001/jamapediatrics.2021.2770
12. https://jogh.org/documents/issue202001/jogh-10-011101.pdf
13. https://www.edweek.org/leadership/in-person-learning-expands-student-absences-up-teachers-work-longer-survey-shows/2020/10(Accessed 5 November 2021)
14. J Am Coll Cardiol Basic Trans Science. 2021 Oct, 6 (9–10) 796–811
15. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/1april2021 (Accessed 5 November 2021)
16. https://doi.org/10.1101/2021.01.23.21250375
17. Thomson H. Children with long covid. New Sci. 2021;249(3323):10–11. doi:10.1016/S0262–4079(21)00303–1