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 Table of Contents  
EDITORIAL
Year : 2022  |  Volume : 12  |  Issue : 2  |  Page : 49-52

Need for COVID-19 vaccination in children


Department of Pediatrics, Max Super Specialty Hospital, Delhi, India

Date of Submission01-Mar-2022
Date of Decision08-Mar-2022
Date of Acceptance10-Mar-2022
Date of Web Publication26-Apr-2022

Correspondence Address:
Dr. Shyam Kukreja
Department of Pediatrics, Max Super Specialty Hospital, Delhi - 110 092
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_24_22

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How to cite this article:
Kukreja S. Need for COVID-19 vaccination in children. Curr Med Res Pract 2022;12:49-52

How to cite this URL:
Kukreja S. Need for COVID-19 vaccination in children. Curr Med Res Pract [serial online] 2022 [cited 2022 May 19];12:49-52. Available from: http://www.cmrpjournal.org/text.asp?2022/12/2/49/343935



Whether all children should be offered vaccination against COVID-19 is a complex issue with no straightforward answer. COVID-19 is generally an asymptomatic or mild disease in children. Older people and adults with comorbidities face the highest risk of severe disease and death. Therefore, this group of individuals was prioritised to receive the vaccination first.

Our country has started vaccinating children in the age group of 15–17 years as data indicate that this group is quite vulnerable to severe COVID-19 disease as young adults. The plan to vaccinate all children above the age of 12 years is in the offing for similar reasons. According to the Centers for Disease Control (CDC) Data Tracker, unvaccinated adolescents aged 12–17 years have eight times higher risk of COVID-19–associated hospitalisation than vaccinated adolescents.[1] The risk in unvaccinated subjects vis-à-vis vaccinated in the age group of 18–49 years is 12 times higher while it is 17 times higher in individuals above 50 years.

However, there is a debate regarding the vaccination of children under 12 years of age. The morbidity and mortality of COVID-19 in this age group are much lower than that seen in older adolescents, adults and the elderly. There is no consensus because the assessment of the benefit versus risk of COVID vaccination in children in this age group is complex. The debate is whether there is merit in vaccinating all children or prioritising some groups among children under 12 years of age based on the available scientific data. COVID-19 pandemic has been quite dynamic with different variants of concern with different reproduction rate (R0) and virulence appearing at different times. Hence, it is deemed necessary to critically monitor the epidemiological situation and accordingly design a strategy and public health approach to controlling it.


  Why Vaccinate Children when Majority Of COVID-19 Infections in Children are Asymptomatic or Mildly Symptomatic? Top


Children have been proportionately less affected by severe COVID-19 disease compared with adults. Several hypotheses[2] have been proposed to explain the more frequent milder illness and low proportion of severe disease in children: (1) lower ACE2 expression (implying lesser binding sites for COVID-19 virus); (2) trained immunity by repeated natural viral infections and vaccinations such as measles, mumps, and rubella and BCG (bacille Calmette-Guerin) vaccine; (3) presence of cross-reactive antibodies produced by common cold-causing coronaviruses; (4) excellent regenerating capacity of the paediatric alveolar epithelium; (5) lower prevalence of comorbidities and risk factors such as smoking and (6) higher levels of melatonin. Due to these protective factors, the global mortality in the paediatric age group has been very low.

Among the 3.5 million COVID-19 deaths reported in the MPIDR COVer AGE database from 79 countries, 0.4% (over 12,300) occurred in children and adolescents under 20 years of age.[3] Of the over 12,300 deaths reported in under 20 years of age, 58% occurred among adolescents aged 10–19 years and 42% among children aged 0–9 years.

Age-disaggregated cases reported to the WHO from 30 December 2019 to 25 October 2021 show that deaths for all ages <25 years represented <0.5% of reported total global deaths due to COVID-19.[4] There were 1797 deaths in children under 5 years, accounting for 0.1% of reported global deaths. However, COVID-19–like pneumonia in children under five years can also commonly occur due to other respiratory infections such as influenza and parainfluenza adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus and other viruses. Therefore, even this small percentage of deaths in this age group may be an overestimation.

In older children and younger adolescents (5–14 years), there were 1328 deaths accounting for 0.1% of reported global deaths, while older adolescents and young adults (15–24 years) reported higher mortality with 7023 deaths accounting for 0.4% of reported global deaths. However, these numbers often include children who were admitted in the hospital with COVID-19 (e.g. meningitis with COVID-19–positive report) and not because of COVID-19 and therefore overestimate the mortality.[4]

From these data, it appears that the direct health benefit of vaccinating younger children would be much lower compared with vaccinating older adolescents and adults considering a lower incidence of severe COVID-19 and deaths in younger age groups. Thus, if the balance of risk and benefit is calculated, then there would be merit in protecting older children above the age of 12 years.


  Need to Vaccinate Children with Comorbidities Top


Two systematic review and meta-analysis of severe COVID-19 infection associated with paediatric comorbidities concluded that these children have a higher risk of severe COVID-19 disease and mortality than children without comorbidities.[5] Data from 42 studies containing 275,661 children without comorbidities and 9353 children with comorbidities were included in this systemic review. Severe COVID-19 was present in 5.1% of children with comorbidities, compared to 0.2% without comorbidities. Hence, there are good reasons to protect children and adolescents at higher risk of becoming seriously ill with COVID-19 infection. The risk factors responsible for causing severe COVID-19 in children in these studies were obesity, diabetes, heart and pulmonary diseases including asthma, neurologic, neurodevelopmental (Down syndrome) and neuromuscular conditions.[5],[6]


  Is There Really a Need to Vaccinate Children in the Current Epidemiological Scenario? Top


Several severe acute respiratory syndrome-coronavirus disease-2 (SARS-CoV-2) seroprevalence studies[7] have been conducted to know whether children and adolescents have been infected at the same rate as adults. These studies show varied results as they were done at different times during the pandemic. A serosurvey done in India after the Delta wave in June–July 2021 demonstrated similar seropositivity rates in children aged 5–18 years (despite closed schools) as adults in the age group of 18–60 years, while adults older than 60 years showed higher seropositivity than other age groups obviously due to immunisation in this age group. Despite equivalent seropositivity in children as adults, children did not report to health-care facilities in similar proportion as adults suggesting high asymptomatic infection in children and high reproduction rate R0 during the second (Delta) wave.

The report of the sixth serosurvey conducted from 24 September to 14 October 2021 in different zones of Delhi among 27,811 participants showed overall positivity of 87.99%.[8] This high seroprevalence was obviously due to the past infection or vaccination or both. Natural infection also played a major role as 80% of the children under 18 years were positive for antibodies as there was no vaccination in this age group. The immunity imparted by natural infection is generally robust enough to a large extent to prevent reinfections, hospitalisations and deaths.[9],[10]


  Would Natural Infection in Unvaccinated Children <12 Years be Protective Enough to Preclude the Need for Vaccination? Top


Observational studies indicate that natural immunity offers even greater protection against COVID-19 infections than fully vaccinated individuals.[9],[10] However, the question regarding the exact duration of this natural immunity is yet to be answered. It is believed that the protection from reinfection would last more than 10 months at least. It has been found in recent research that individuals who recovered from SARS-CoV about 17 years ago still have memory T cells against SARS-CoV antigens.[11] Similarly, it has been found that SARS-CoV-2 79% genomic similarity with SARS-C infection also induces durable T cell immunity against several SARS-CoV-2 spike protein epitopes and other antigenic targets on the SARS-CoV-2. The role of T cell immunity is to protect against severe disease, while the presence of sufficient antibodies (B cell immunity) provides protection against symptomatic infection. Antibodies decline over few months, while cellular immunity tends to last longer. Whether it would last as long as at least 17 years as in SARS-CoV or shorter, it is not known. Whether there would be a need to have repeated vaccinations to boost immunity against future variants as in the case of influenza (due to antigenic drift) or would immunity following natural COVID-19 infection last long enough (as after measles infection) to protect against severe disease? We would know the answers to these pertinent questions with more data in the near future.


  RISK of Multisystem Inflammatory Syndrome in children (MIS-C) Following Vaccination Top


MIS-C is a serious illness that usually appears 2–6 weeks after COVID-19 infection. American Academy of Pediatrics reported that more than 12.5 million children had contracted COVID-19 nationwide during the pandemic, and there have been 6851 MIS-C cases along with 59 deaths, according to the CDC. Now that COVID-19 vaccines have been introduced to the paediatric population, there were concerns that vaccination such as natural infection could also trigger multisystem inflammatory response. There are uncertainties surrounding MIS-C immunopathogenesis and a theoretical risk that antibodies induced by COVID-19 vaccination could induce MIS-C. So far, there have been no reports of an increased occurrence of MIS-C following initiation of vaccination in the age group of 15–18 years in India. Vaccination surveillance data from the USA after introducing the mRNA vaccines have also not detected excess cases of MIS-C.


  As Risk Of Severe COVID-19 in Children Under 12 Years is Very Low. If Vaccination is Planned in This Age Group, The Vaccines Must be Extremely Safe. Do we Have Such COVID-19 Vaccines? Top


Several vaccines are being used widely in adults in different parts of the world. Some of these vaccines have received emergency use authorisation by regulatory authorities for use in children and adolescents. Whether these vaccines are equally safe in children has been a point of debate. The two most widely used vaccines in adults are the adenovirus vector vaccine and mRNA vaccines. The use of adenoviral-vector vaccines is associated with the risk of thrombosis with thrombocytopaenia syndrome (TTS) in younger adults (particularly females) compared to older adults. Although the risk of TTS has been reportedly low, the researchers got discouraged from trying this vaccine in children and adolescents.

The mRNA vaccine has been identified to be associated with an increased risk of myopericarditis. It was estimated that among 12–17-year-olds, the rate ratio for myocarditis/pericarditis was elevated during days 0–7 after dose 2 of mRNA Pfizer vaccine, and the excess risk was 70 cases per million after the second doses.[11] While, another report from Kaiser Permanente suggested a very high risk of 377.4 cases per million in boys aged 12–17 years.[12] However, data suggest that these cases of myocarditis and pericarditis following vaccination are generally mild and respond well to conservative treatment, though long-term outcome is not known.

Covaxin (whole-virion inactivated vaccine by Bharat Biotech) is approved by the Drugs Controller General of India for children aged 12 years and above; currently, it is the only vaccine being used in children aged 15–17 years in India. Two other promising vaccines likely to become available very soon in India are protein subunit vaccines, namely Corbevax (Biological E Ltd) and Covavax (Serum Institute of India). These three vaccines appear to be safer for use in children.


  Prevention of MIS-C Following Vaccination Top


According to a recent report by the CDC, Pfizer-BioNTech vaccine was found to be effective in preventing MIS-C; the estimated effectiveness of two doses of the Pfizer-BioNTech vaccine against MIS-C was 91% (95% CI 78%-97%).[13] This study was done in 24 U.S. paediatric hospitals during the Delta wave in July–December 2021.

In India, most paediatric centres have witnessed a spurt of MIS-C cases coinciding with the past two COVID-19 waves, and these cases consistently appeared about two to 6 weeks after each COVID-19 wave. Now that the Omicron surge is waning, paediatric hospitals are closely monitoring MIS-C cases. So far, it appears that the Omicron wave has not triggered MIS-C cases as in the last two COVID-19 waves. There could be two explanations for this observation – Omicron infection in already high seropositivity paediatric population prevented the immunological trigger or Omicron is not pathogenic or invasive enough to trigger the immune system to cause MIS-C.


  Author'S Viewpoint Top


  • Currently, if we weigh up the risks and benefits, there is merit in vaccinating older children above the age of 12 years as planned by the Government of India.
  • There is no consensus regarding vaccination of children under 12 years of age as the assessment of benefit versus risk of COVID-19 vaccination in children in this age group is complex.
  • The children with comorbidities have high risk of severe COVID-19 disease. It is crucial to vaccinate these children.
  • According to the latest 6th serosurvey conducted in September–October 2021, most children (80%) have acquired natural immunity and this immunity in all probability would have expanded to even larger population, including children following the Omicron wave, which was many times more transmissible than previous waves.
  • According to the current knowledge, the immunity imparted by natural infection to a majority of the paediatric population cannot be trusted for long-term protection. Further, there is a high burden of undiagnosed comorbidities in the paediatric population of low-to-middle-income countries. In the near future, very promising protein subunits vaccines are going to be introduced in the 12–17 years of age group in addition to already in use whole-virion–inactivated vaccine 15–17 years of age group. If these vaccines prove to be very safe and immunogenic in the paediatric population, then this would pave the way toward widening vaccination net to include all children in the near future.
  • Learning from the past 2 years of pandemic is that there is a need to keep a close watch on the emergence of new more virulent variants, which would necessitate a continual re-evaluation of vaccination strategies.
  • Once infected, the vaccinated individuals transmit COVID-19 similar to unvaccinated individuals. During the Delta and Omicron surge, vaccinated and unvaccinated individuals had similar viral loads in the nasopharynx.[14] Thus, there is a greater need to have better vaccines in the future, which could also prevent transmission of the virus in addition to providing individuals greater and longer protection against new emerging variants so that the control of outbreaks in the communities is possible.
  • So far, the paediatric population has been relatively safe against different COVID-19 variants; we need to prepare for future variants which may not be as gentle to children as past variants. There would be a need to have universal vaccination of children against COVID-19 in the near future.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
CDC COVID Data Tracker. Available from: https://COVID.cdc.gov/COVID-data-tracker/#datatracker-home.  Back to cited text no. 1
    
2.
Zimmermann P, Curtis N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch Dis Child 2020;10.1136/archdischild-2020-320338.  Back to cited text no. 2
    
3.
Child Mortality and COVID-19, Jan 2022, UNICEF Data. Available from: https://data.unicef.org/topic/child-survival/COVID-19/. [Last accessed on 2022 Feb 22].  Back to cited text no. 3
    
4.
World Health Organization. Interim Statement on COVID-19 Vaccination for Children and Adolescents. Available from: https://www.who.int/news/item/24-11-2021-interim-statement-on-COVID-19-vaccination-for-children-and-adolescents. [Last accessed on 2022 Feb 22].  Back to cited text no. 4
    
5.
Tsankov BK, Allaire JM, Irvine MA, Lopez AA, Sauvé LJ, Vallance BA, et al. Severe COVID-19 infection and pediatric comorbidities: A systematic review and meta-analysis. Int J Infect Dis 2021;103:246-56.  Back to cited text no. 5
    
6.
Shi Q, Wang Z, Liu J, Wang X, Zhou Q, Li Q, et al. Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis. EClinicalMedicine 2021;41:101155.  Back to cited text no. 6
    
7.
Gaythorpe KA, Bhatia S, Mangal T, Unwin HJ, Imai N, Cuomo-Dannenburg G, et al. Children's role in the COVID-19 pandemic: A systematic review of early surveillance data on susceptibility, severity, and transmissibility. Sci Rep 2021;11:13903.  Back to cited text no. 7
    
8.
Sharma P, Basu S, Mishra S, Gupta E, Aggarwal R, Kale PR, et al. SARS-CoV-2 seroprevalence in Delhi, India: September October 2021: A population based seroepidemiological study. medRxiv 2021; [doi: 10.1101/2021.12.28.21268451].  Back to cited text no. 8
    
9.
Pilz S, Chakeri A, Ioannidis JP, Richter L, Theiler-Schwetz V, Trummer C, et al. SARS-CoV-2 re-infection risk in Austria. Eur J Clin Invest 2021;51:e13520.  Back to cited text no. 9
    
10.
Kojima N, Klausner JD. Protective immunity after recovery from SARS-CoV-2 infection. Lancet Infect Dis 2022;22:12-4.  Back to cited text no. 10
    
11.
Singer ME, Taub IB, Kaelber DC. Risk of myocarditis from COVID-19 infection in people under age 20: A population-based analysis. medRxiv 2021;doi: 10.1101/2021.07.23.21260998.  Back to cited text no. 11
    
12.
Sharff K, Dancoes DM, Longueil JL, Johnson ES, Lewis PF. Risk of myopericarditis following COVID-19 mRNA vaccination in a large integrated health system: A comparison of completeness and timeliness of two methods. medRxiv 2021. [doi: 10.1101/2021.07.23.21260998].  Back to cited text no. 12
    
13.
Zambrano LD, Newhams MM, Olson SM, Halasa NB, Price AM, Boom JA, et al. Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA vaccination against multisystem inflammatory syndrome in children among persons aged 12-18 years – United States, July-December 2021. MMWR Morb Mortal Wkly Rep 2022;71:52-8.  Back to cited text no. 13
    
14.
Riemersma KK, Grogan BE, Kita-Yarbro A, Halfmann P, Kocharian A, Florek KR, et al. Shedding of infectious SARS-CoV-2 despite vaccination when the delta variant is prevalent – Wisconsin, July 2021. medRxiv 2021; Available from: https://doi.org/10.1101/20210.07.31.21261387.2021.07.31.21261387. [Last accessed on 2022 Mar 17].  Back to cited text no. 14
    




 

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