Are COVID jabs the best way to protect children?

Posted byimperialbiosciencereviewPosted inPharmaceuticals

By Jasper Kan

Since it’s first recorded outbreak in China, SARS-CoV-2 (COVID-19) has wreaked havoc among humanity, bringing numerous casualties and the world to a standstill. While many (including governments) believe indiscriminate vaccination is the only way out, others doubt the unknown effects that a novel vaccine exerts. This doubt is particularly concerning for the underaged, whom are still processing to physical maturity. This raises the question: are COVID-19 jabs the best way to protect children?

During pregnancy, the immune system is altered for the mother, e.g., levels of CD4+ and CD8+ lymphocytes decrease.1 This potentially undermines immunity of pregnant women and foetuses against COVID-19. Nonetheless, vaccinations theoretically trigger production of antibodies which pass through the placenta. To investigate vaccine effectiveness (VE) to protect infants from Delta and Omicron strains, an observational study was carried out to investigate the protection effect of maternal vaccination after pregnancy and ≥14 days before delivery for 0–6-month-old infants.1 In terms of preventing infant hospitalisation, VE was only 32% if it was completed in the first 20 weeks, but then increased to 80% if it was completed 21 weeks and onwards. However, if infants were COVID-positive and hospitalised, maternal vaccination would be less effective to prevent serious cases. For vaccinated mothers whose children tested positive (n=28), 17.9% required intensive care. For unvaccinated mothers whose children were positive (n=148), the figure was 25.8%. The percentages were even more similar for infants who required life support – 14.3% and 14.6% respectively. 

For older children, vaccine effectiveness was investigated in other papers. One of the measurements used was antibody titres, in which patient sera (containing antibodies) were diluted to certain folds and incubated with SARS-CoV-2 strains, after that the sera were checked to see if any viral-specific antibodies were detected. The higher the value, the more dilutions needed to make the antibody undetectable, which infers high effectiveness of the treatment.

Prior to Omicron, an evaluation article commended the effectiveness of phase trials of 10 μg double-dose BNT162b2 in 5-to-11-year-olds. 9 Vaccine efficacy was 90.7%, and the geometric mean ratio of neutralizing titres (GMT) rose for 118.2-fold to 1198 after a month of the second dose, compared with the baseline value of 11 from placebo injections of subjects, after a 1.1-fold rise in ratio. This shows that BNT162b2 was effective in augmenting adaptive immunity at that time.

In another paper issued amid the new Omicron variant, it was discovered that recently recovered child patients did not have significant difference with double-vaccinated children, in terms of results from the microneutralisation (MN) assay done after diluted serum was exposed to variants for 1 hour. 2 This justifies the association between effects of both treatments, and data of recovered child patients could be considered as double-vaccinated. Thus, the age range investigated was extended to 2.6-17.9. Compared with the ancestral lineage, double vaccinations had significant reductions on MN titres, and was especially ineffective against the mainstream Omicron variant, with the majority having MN titres ≤10. The antibodies produced by children are more predominantly anti-spike(S) to prevent viral entry, but 30 out of the 50 mutations in Omicron were on S-proteins, which could render original epitopes useless to bind and initiate responses, and attribute to the low effectiveness. 3,4

Apart from the questionable effectiveness, another main cause of vaccine hesitation among parents revolves around side effects, as cases of severe side effects like myocarditis appeared to associate with COVID jabs. 5 Take mRNA vaccines (like the BNT162b2) as an example, a glycoprotein part of the S-protein has its nucleoside modified before injected in vivo inside a lipid nanoparticle. While it boosts adaptive immunity and allows recognition of viruses carrying the same S-protein, antibodies produced by vaccines may also target myocardial α-myosin heavy chain, a protein similarly structured as the intended target. Such unintended responses are particularly exacerbated in young males – apart from their highly vigorous immune responses, males produce much higher amounts of testosterone, which can inhibit anti-inflammatory immune cells and augment T-cell responses. Coupled with possible genetic factors in some vaccine receivers, vaccine hesitation is not without grounds. 

Reports on side effects of vaccinating 12-to-17-year-olds show that myopericarditis after dose 2 was most common. While patients’ sexes were not known, the incidence of myo/pericarditis was higher in 12-to-15-year-olds (0.01%) compared with others (0.008%), which is the same risk as of contracting myocarditis by smallpox vaccinations which has been used for centuries.8 Although still higher than the observed baseline rate of myocarditis, patients generally had mild symptoms. Also, with reference to adult data, the risk factor of myocarditis associated with COVID-19 was about 6 times higher than that with 1 dose of BNT162b2.6,7 I believe this can be explained by the increased amount of S-proteins associated with the increased ability for COVID-19 to grow and multiply in patients, which causes the production of more antibodies, eventually increasing the chance of an inadvertent binding to myocardial proteins. If this hypothesis is established, similar fates would be encountered by adolescents as well, and the benefits of mRNA vaccines outweigh their risks. Methods, like increasing the gap between the 2 doses and reducing dose concentration for dose 2, are also suggested to mitigate side effects.

In 5-to-11-year-olds, short term side effects were predominantly mild to moderate and recovered in days, such as injection site pain. Adverse events were reported in 9.2% of placebo recipients and a slightly higher, 10.9% of BNT162b2 recipients. One example was lymphadenopathy, which accounted for <1% for each group. This proves the low incidence of vaccine side effects in this age group.9

In a nutshell, although one can be rest assured for the side effects, as it is mostly mild especially compared with the increased incidence of myocarditis in COVID patients, the effectiveness of the vaccine is now becoming questionable due to the Omicron variant, which harbours mutations evading defence mechanisms in immune systems of a child. I would put forward a cautious attitude for immunising children from Omicron through vaccinations and wait for evaluations for the new vaccines targeting Omicron.10

References:

  1. Halasa NB, Olson SM, Staat MA, Newhams MM, Price AM, Boom JA, et al.; Overcoming COVID-19 Investigators; Overcoming COVID-19 Network. Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19-Associated Hospitalization in Infants Aged <6 Months – 17 States, July 2021-January 2022. MMWR Morb Mortal Wkly Rep. 2022 Feb 18;71(7):264-270. doi: 10.15585/mmwr.mm7107e3. PMID: 35176002; PMCID: PMC8853480.
  2. L Chen, G.T. Chua, L. Lu, B.P.C. Chan, J.S.C. Wong, C.C.K. Chow, et.al,(2022) Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine, Emerging Microbes & Infections, 11:1, 543-547, DOI: 10.1080/22221751.2022.2035195 
  3. Weisberg, S.P., Connors, T.J., Zhu, Y. et al. Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum. Nat Immunol 22, 25–31 (2021). https://doi.org/10.1038/s41590-020-00826-9
  4. Hagen A., How Ominous Is the Omicron Variant (B.1.1.529)?. American Society For Microbiology. 2021. https://asm.org/Articles/2021/December/How-Ominous-is-the-Omicron-Variant-B-1-1-529. [17 Mar 2022]
  5. Long S.S., Important Insights into Myopericarditis after the Pfizer mRNA COVID-19 Vaccination in Adolescents. The Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2021.07.057
  6. Heymans, S., Cooper, L.T. Myocarditis after COVID-19 mRNA vaccination: clinical observations and potential mechanisms. Nat Rev Cardiol 19, 75–77 (2022). https://doi.org/10.1038/s41569-021-00662-w
  7. Schauer J., Buddhe S., Colyer J., Law Y., Chikkabyrappa S.M., Portman M.A., Myopericarditis After the Pfizer Messenger Ribonucleic Acid Coronavirus Disease Vaccine in Adolescents. The Journal of Pediatrics. https://doi.org/10.1016/j.jpeds.2021.06.083
  8. Abu Mouch, S., Roguin, A., Hellou, E., Ishai, A., Shoshan, U., Mahamid, L., Zoabi, M., Aisman, M., Goldschmid, N., & Berar Yanay, N. (2021). Myocarditis following COVID-19 mRNA vaccination. Vaccine, 39(29), 3790–3793. https://doi.org/10.1016/j.vaccine.2021.05.087
  9. Emmanuel B. Walter E.B., Talaat K.R., Sabharwal C., Gurtman A., Lockhart S. et. al., Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. The New England Journal of Medicine. N Engl J Med 2022; 386:35-46. DOI: 10.1056/NEJMoa2116298
  10. Spencer Kimball. Pfizer CEO says omicron vaccine will be ready in March. https://www.cnbc.com/2022/01/10/covid-vaccine-pfizer-ceo-says-omicron-vaccine-will-be-ready-in-march.html [Accessed 20 Mar 2022]