Why vaccinate children against COVID-19?

The World Health Organization (WHO) Roadmap identifies priority-use groups to optimize the public health impact through recommendations that seek to ensure equitable distribution and urgent vaccine access to those most at-risk, no matter where they live. To achieve the primary objectives of averting deaths by preventing severe disease and protecting health system impact by reducing hospital admissions and preventing intensive care from becoming overwhelmed, older persons and adults with comorbidities were allocated to the highest priority-use category. Children and adolescents with underlying health conditions that put them at higher risk of severe COVID-19 outcomes are in the medium priority-use groups. Healthy children were allocated to the lowest priority-use group based on their lower risk of COVID-19-related severe disease and death. Age-disaggregated cases reported to WHO from December 30, 2019, to July 4, 2022, showed that children less than 5 years of age represent 2% (6,607,392) of reported global cases and 0.1% (2,627) of reported global deaths; older children and younger adolescents (5–14 years) account for 11% (28,256,515) of cases and 0.1% (1,935) of deaths, while older adolescents and young adults (15–24 years) represent 14% (37,438,185) of cases and 0.4% (9,019) of deaths [2]WHO. WHO interim statement on COVID-19 vaccination for children and adolescents Geneva: World Health Organization, 2021. (Accessed July 12 2022).. Patients less than 25 years represented less than 0.6% of reported global deaths.

The global burden of pediatric COVID-19 is not insignificant. According to United Nations Children’s Fund (UNICEF), nearly 20,000 children (under age 20) have died from COVID-19 globally [3]UNICEF. For Every Child. Child Mortality and COVID-19, 2022. (Accessed July 12 2022)., and even this number is considered an underestimate. More than 1,000 pediatric deaths have occurred in the USA alone [4]Centers for Disease Control. Data.(CDC). Provisional COVID-19 Deaths: Focus on Ages 0-18 Years. CDC. 2022. (Accessed July 10 2022)., such that COVID-19 outranks many other causes of vaccine-preventable deaths in the USA. But case counts and death rates are not the only outcomes relevant to the health and well-being of children. Despite a lower risk of severe disease, the COVID-19 pandemic and its control measures disproportionately affected children and adolescents. The most damaging and long-term effects relate to school closures, which disrupt the provision of educational (and in some cases health and nutritional) services and increase emotional distress and mental health problems [5]United Nations Children’s fund (UNICEF). Framework for Reopening Schools. UNICEF, 2022. (Accessed July 10 2022).. Consistent and continuous school attendance is critical to the well-being and life prospects of children and parental participation in the economy.

Beyond educational setbacks, school closures and stay-at-home orders have been associated with increased domestic violence [5]United Nations Children’s fund (UNICEF). Framework for Reopening Schools. UNICEF, 2022. (Accessed July 10 2022).United Nations Children’s fund (UNICEF). Framework for Reopening Schools. UNICEF, 2022. (Accessed July 10 2022)., including sexual assault, adolescent pregnancy, and child marriage. These traumas are further exacerbated by the increased probability of missing further education and of poor pregnancy outcomes. School closures also lead to loss of access to a wide range of school-provided services, including school meals, monitoring of health and welfare, social skills training, and services targeted to children with special needs. As schools moved online, impoverished children experienced dramatic educational setbacks [5]United Nations Children’s fund (UNICEF). Framework for Reopening Schools. UNICEF, 2022. (Accessed July 10 2022).United Nations Children’s fund (UNICEF). Framework for Reopening Schools. UNICEF, 2022. (Accessed July 10 2022)., contributing to inequalities and long-term hardship.

While school closures during the peak of a pandemic may contribute to rapidly flattening the curve, greater overall health and well-being benefits come from keeping schools open by implementing comprehensive, multi-layered measures to prevent the introduction and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in educational settings. That is why, very early on in the pandemic, WHO and UNICEF advised against school closures and developed guidance on how to minimize transmission in schools and keep schools open [5]United Nations Children’s fund (UNICEF). Framework for Reopening Schools. UNICEF, 2022. (Accessed July 10 2022)..

Vaccinating school-aged children has been recommended in some countries to help minimize school disruptions by reducing the number of infections at school and the number of children required to miss school because of quarantine requirements. Vaccinating children and adolescents has also been advocated to reduce intergenerational transmission, an important additional public health objective. Prior to the emergence of the Delta variant, the risk of symptomatic cases in household contacts of vaccinated cases was reported to be about 50% lower than that among household contacts of unvaccinated cases [6]Harris RJ, Hall JA, Zaidi A, Andrews NJ, Dunbar JK, Dabrera G. Effect of Vaccination on Household Transmission of SARS-CoV-2 in England. N. Engl. J Med. 2021; 385(8),759–60. . However, the impact of vaccination on reducing transmission in the context of the more transmissible Delta and Omicron variants appears to be significantly lower and less durable [7]Singanayagam A, Patel M, Charlett A et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro. Surveill. 2020; 25(32), 2001483. . As such, the use of current COVID-19 vaccines to directly protect teachers, family members, and other adult contacts of children and adolescents is likely to have a greater impact on reducing severe COVID-19 and deaths in the contacts of children than vaccinating children to indirectly protect their contacts.

The emergence and spread of the Omicron variant showed that hospitalizations in younger children (all generally unvaccinated) became more frequent, reflecting increasingly widespread community transmission. Although children and adolescents can experience prolonged clinical symptoms (known as ‘long-COVID’, or post-acute sequelae of SARS-CoV-2 infection), the frequency and characteristics of these conditions remain under investigation. One large study from London found that approximately 14% of COVID-19-infected children suffer symptoms lasting more than 15 months [8]Wise J. Long covid: One in seven children may still have symptoms 15 weeks after infection, data show. BMJ. 2021; 374, n2157. . Additionally, a hyperinflammatory syndrome, referred to as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 in Europe and multisystem inflammatory syndrome in children (MIS-C) in the USA, may not be as rare as previously believed [9]Centers for Disease Control (CDC). Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States. CDC. 2022. (Accessed July 10 2022)., and has been reported to occur worldwide and complicate recovery from COVID-19 [10]Jiang L, Tang K, Levin M et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect. Dis. 2020; 20(11), e276-e88. .

However, there is an evidence gap that must be acknowledged – the preponderance of evidence on the risk of severe COVID-19 and death in children and adolescents comes from studies in high-resource settings. One systematic review suggests that there may be a larger impact of pediatric COVID-19-related fatality in low- and middle-income countries (LMICs) versus high-income countries (HICs) [11]Kitano T, Kitano M, Krueger C et al. The differential impact of pediatric COVID-19 between high-income countries and low- and middle-income countries: A systematic review of fatality and ICU admission in children worldwide. PLoS One. 2021; 16(1), e0246326. . Clearly, we need more research on the direct health and indirect societal impacts of COVID-19 in children and their families in LMICs.

Still another consideration is the increasing availability of COVID-19 vaccine doses and new vaccines released for children under emergency use authorization. Benefit–risk assessments for this age group must be conducted rigorously for each of the COVID-19 vaccines that have received emergency use authorization. As COVID-19 vaccines become more readily available globally and vaccine coverage rates among high-priority use groups increase, there is now a stronger rationale for vaccinating children. Along those lines, some LMICs have begun pediatric or adolescent COVID-19 immunization campaigns, in some cases, such as in India, using locally produced vaccines. With increasing seroprevalence rates reported globally, especially among children and adolescents, vaccine strategies need to be adapted. The number of vaccine doses, inter-dose interval, and need for booster may differ in settings with high seroprevalence [1]WHO. WHO SAGE Roadmap for prioritizing uses of COVID-19 vaccines. Geneva: World Health Organization, 2022. (Accessed Sep 2022)..

Taking all the above into consideration, the decision to vaccinate healthy children and adolescents must account for prioritization to first fully protect higher priority-use groups (e.g., older adults, adults with comorbidities, health workers and essential workers) through primary vaccination series, and, as vaccine effectiveness declines with time, through booster doses [1]WHO. WHO SAGE Roadmap for prioritizing uses of COVID-19 vaccines. Geneva: World Health Organization, 2022. (Accessed Sep 2022).. Although benefit–risk assessments clearly underpin the benefit of vaccinating all age groups, including children and adolescents, the direct health benefit of vaccinating healthy children and adolescents is lower compared with vaccinating older adults due to the lower incidence of severe COVID-19 and deaths in younger persons. While at the patient level, decisions regarding vaccinating a child must take into account individual circumstances and values and local considerations, at a societal and global level, vaccinating children is a less urgent public health priority at a time when many higher priority-use groups have not yet achieved high levels of access and coverage.

Regardless of vaccination, countries’ strategies related to COVID-19 control should facilitate children’s participation in education and other aspects of social life, and minimize loss of in-person interactions [12]World Health Organization (WHO), United Nations Children’s fund (UNICEF) , United Nations Educational, Scientific and Cultural Organization (UNESCO). Considerations for school-related public health measures in the context of COVID-19: annex to considerations in adjusting public health and social measures in the context of COVID-19. WHO, UNICEF, UNESCO.(Sep 14 2020). . (Accessed July 10 2022)..

References

1. WHO. WHO SAGE Roadmap for prioritizing uses of COVID-19 vaccines. Geneva: World Health Organization, 2022. (Accessed Sep 2022).  Crossref

2. WHO. WHO interim statement on COVID-19 vaccination for children and adolescents Geneva: World Health Organization, 2021. (Accessed July 12 2022).  Crossref

3. UNICEF. For Every Child. Child Mortality and COVID-19, 2022. (Accessed July 12 2022).  Crossref

4. Centers for Disease Control. Data.(CDC). Provisional COVID-19 Deaths: Focus on Ages 0-18 Years. CDC. 2022. (Accessed July 10 2022).  Crossref

5. United Nations Children’s fund (UNICEF). Framework for Reopening Schools. UNICEF, 2022. (Accessed July 10 2022).  Crossref

6. Harris RJ, Hall JA, Zaidi A, Andrews NJ, Dunbar JK, Dabrera G. Effect of Vaccination on Household Transmission of SARS-CoV-2 in England. N. Engl. J Med. 2021; 385(8),759–60.  Crossref

7. Singanayagam A, Patel M, Charlett A et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro. Surveill. 2020; 25(32), 2001483.  Crossref

8. Wise J. Long covid: One in seven children may still have symptoms 15 weeks after infection, data show. BMJ. 2021; 374, n2157.  Crossref

9. Centers for Disease Control (CDC). Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States. CDC. 2022. (Accessed July 10 2022).  Crossref

10. Jiang L, Tang K, Levin M et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect. Dis. 2020; 20(11), e276-e88.  Crossref

11. Kitano T, Kitano M, Krueger C et al. The differential impact of pediatric COVID-19 between high-income countries and low- and middle-income countries: A systematic review of fatality and ICU admission in children worldwide. PLoS One. 2021; 16(1), e0246326.  Crossref

12. World Health Organization (WHO), United Nations Children’s fund (UNICEF) , United Nations Educational, Scientific and Cultural Organization (UNESCO). Considerations for school-related public health measures in the context of COVID-19: annex to considerations in adjusting public health and social measures in the context of COVID-19. WHO, UNICEF, UNESCO.(Sep 14 2020). . (Accessed July 10 2022).  Crossref

Affiliations

David C Kaslow
PATH Essential Medicines,
PATH Seattle, WA, USA

Carolina Batista
Médecins Sans Frontières,
Rio de Janeiro, Brazil
and
Baraka Impact Finance,
Geneva, Switzerland

Maria Elena Bottazzi
Texas Children’s Hospital Center for Vaccine Development,
Baylor College of Medicine,
Houston, TX, USA

Onder Ergonul
Koc University Research Center for Infectious Diseases,
Istanbul, Turkey

J Peter Figueroa
University of the West Indies,
Mona, Kingston, Jamaica

Mayda Gursel
Middle East Technical University,
Ankara, Turkey

Mazen Hassanain
College of Medicine,
King Saud University,
Riyadh, Saudi Arabia

Peter Hotez
Texas Children’s Hospital Center for Vaccine Development,
Baylor College of Medicine,
Houston, TX, USA

Gagandeep Kang
Christian Medical College,
Vellore, India

Bhavna Lall
University of Houston College of Medicine,
Houston, TX, USA

Heidi Larson
London School of Hygiene & Tropical Medicine,
London, UK

Denise Naniche
ISGlobal-Barcelona Institute for Global Health-Hospital Clinic,
University of Barcelona,
Spain

Timothy Sheahan
University of North Carolina,
Gillings School of Global Public Health,
Chapel Hill, NC, USA

Samba O Sow
Center for Vaccine Development,
Bamako, Mali
and
University of Maryland,
MD, USA

Nathalie Strub-Wourgaft
London School of Hygiene & Tropical Medicine,
London, UK
and
Drugs for Neglected Diseases Initiative,
Geneva, Switzerland

Prashant Yadav
Center for Global Development,
Washington, DC, USA
Harvard Medical School,
Boston, MA, USA
and
Affiliate Professor,
Technology and Operations Management, INSEAD

Annelies Wilder-Smith
London School of Hygiene & Tropical Medicine,
London, UK
and
Heidelberg Institute of Global Health,
University of Heidelberg,
Heidelberg, Germany

Authorship & Conflict of Interest

Contributions: All named authors take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Acknowledgements: None.

Disclosure and potential conflicts of interest: Batista C was elected international board member at Doctors Without Borders (Medècins Sans Frontieres) Hotez P and Bottazzi ME are co-inventors of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by BCM non-exclusively and with no patent restrictions to several companies committed to advancing vaccines for low- and middle-income countries. The co-inventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income. Hotez P and Bottazzi ME declare they are developers of the RBD219-N1C1and RBD203-N1 technologies, and that Baylor College of Medicine (BCM) licensed RBD219-N1C1 to Biological E, an Indian manufacturer, for further advancement and licensure. Similar licensing agreements are also in place with other partners for both RBD219-N1C1 and RBD203-N1. The research conducted in this paper was performed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Gursel M participates in one of eight SARS-CoV-2 vaccine development projects supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) since March 2020. Hassanain M is Founder and Managing Director of SaudiVax. Figueroa JP, Kang G and Kaslow DC are members of the WHO SAGE Working Group on COVID-19 vaccines. Kang G is independent director appointed by the Wellcome Trust, MSD Wellcome Trust Hilleman Laboratories Private Limited, and Vice Chair of the Board, Coalition of Epidemic Preparedness Innovations (CEPI). Kaslow DC reports grants from Bill and Melinda Gates Foundation (BMGF) and grants from CEPI, HL reports grants and honoraria from GlaxoSmithKline for training talks and from Merck as a member of the Merck Vaccine Confidence Advisory Board, grants from J&J outside the submitted work. Wilder-Smith A serves as Consultant to WHO. The views presented here reflect her views and not necessarily those of WHO. Sheahan T reports grants from National Institute of Allergy and Infectious Disease and Fast Grants and research contracts from GlaxoSmithKline, and ViiV Healthcare. Larson H Merck has a grant to investigate Health Care Professional vaccine hesitancy in the Mid-East and Europe region, also has a grant from Astra Zeneca to organize webinars in multiple European countries with HCPs to discuss, address Covid vaccine concerns with relevant experts, a grant from the UK Cabinet office to lead academic coalition to investigate and address social media concerns/anti-vaccine trends around covid vaccine and lastly a grant from Euro Commission to map 2022 vaccine confidence in both routine and COVID vaccines across 27 EU countries and compare to pre Covid confidence data. Sow S reports grants from Ansun BioPharma, Astellas Pharma, Cidara Therapeutics, F2G, Merck, T2 Biosystems, Shire Pharmaceuticals, Shionogi, and Gilead Sciences, outside the submitted work; and personal fees from Amplyx Pharmaceuticals, Acidophil, Janssen Pharmaceuticals, Reviral, Intermountain Healthcare, Karyopharm Therapeutics, Immunome, Celltrion, and Adagio outside the submitted work. Yadav P has grants from Open Philanthropy Partners to improve access to oral antivirals in LMICs and Bill & Melinda Gates Foundation to improve the supply chain for pathogen genomic sequencing in Africa. He also has consulting fees with Impact4Development Inc. All other authors declare no conflict of interests. The authors’ views and opinions in the editorial do not necessarily represent the views, decisions, or policies of the institutions, universities, or health systems with which they are affiliated.

Funding declaration: The authors received no financial support for the research, authorship and/or publication of this article.

Article & copyright information

Copyright: Published by Vaccine Insights under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Attribution: Copyright © 2022 Lancet Commission on COVID-19 Vaccines and Therapeutics Task Force. Published by Vaccine Insights under Creative Commons License Deed CC BY NC ND 4.0.

Article source: Invited; externally peer reviewed.

Submitted for peer review: Sep 13 2022; Revised manuscript received: Sep 15 2022; Publication date: Oct 17 2022.