Intention to Vaccinate against COVID-19 in Adolescents: A Systematic Review

Background: Multiple COVID-19 vaccines have been approved for use in adolescents; these vaccines play a critical role in limiting the transmission and impact of COVID-19. This systematic review aims to summarize the willingness of adolescents aged 10 to 19 years to receive the COVID-19 vaccination and the factors influencing their decision. Methods: A search of literature published between January 2018 and August 2022 was performed in Medline©, EMBASE©. and CINAHL© electronic databases. Studies published in English that assessed adolescents’ intentions to receive the COVID-19 vaccine were included. Qualitative studies and those unrelated to the COVID-19 vaccine were excluded. The study was conducted based on the PRISMA guidelines. Results: Of the 1074 articles retrieved, 13 were included in the final review. Most studies were conducted in the US (n = 3) and China (n = 3). The pooled prevalence of COVID-19 vaccine acceptance among adolescents was 63% (95% CI: 52–73%). Factors influencing intent to vaccinate were divided into five categories: “Socio-demographic determinants”; “Communication about COVID-19 pandemic and vaccination”; “COVID-19 vaccine and related issues”; “COVID-19 infection and related issues” and “Other determinants”. The enablers were sociodemographic factors including older age, higher education level, good health perception, and parental norms in terms of parental vaccination acceptance; perceived vaccine effectiveness and safety; a desire to protect themselves and others; recent vaccination; and anxiety. The barriers were concerns over vaccine effectiveness, safety, and long-term side effects; low perceived necessity and risk of infection; and needle phobia. Conclusions: This review highlighted that adolescents’ intent to vaccinate is driven by a desire to protect themselves and others. However, concerns over vaccine effectiveness, safety, and long-term side effects hinder COVID-19 vaccine uptake. To improve vaccination acceptance, policymakers should address adolescents’ concerns via more targeted public health messaging, while schools should leverage peer norms to positively influence vaccination intent.


Introduction
The highly contagious coronavirus 2019  continues to pose a global health threat, with transmission and mutations contributing to increased morbidity and mortality [1]. As of February 2023, more than 755 million people have been infected with COVID-19 [2], with children and adolescents representing approximately a fifth of these cases [3].
The COVID-19 vaccine has been proven to be safe in adolescents with predominantly mild to moderate adverse reactions such as injection-site pain, headache, fever, and fatigue. Adolescents also mounted a stronger or non-inferior immune response to the vaccine when

Data Collection and Study Selection
All studies obtained from the listed databases were exported to EndNote, and duplicates were removed prior to screening. Two researchers (PO and SYT) independently screened the titles and abstracts of the exported studies according to the inclusion and exclusion criteria. The full text of abstracts and titles was extracted for review if they were ambiguous. Full texts were then extracted for all remaining studies using the Nanyang Technological University Library and assessed for eligibility.

Inclusion Criteria
Observational studies published in English involving participants aged 10 to 19 years and their intention to receive the COVID-19 vaccine as defined by vaccine acceptance, willingness, or hesitancy were included.

Exclusion Criteria
Non-observational studies, such as purely qualitative studies and those unrelated to the COVID-19 vaccine, were excluded.

Data Extraction
Two reviewers (PO and SYT) independently conducted the extraction, with discrepancies resolved by a third researcher (NCT). The findings of interest were study design, study population, reported outcomes (vaccine willingness/acceptance, or hesitancy), enablers, and barriers to intention to receive the COVID-19 vaccine. Enablers and barriers refer to factors that positively and negatively contribute to the intention to receive the COVID-19 vaccination, respectively.

Risk of Bias Appraisal
The included studies were independently appraised by the two researchers (PO and SYT), with any discrepancies resolved by a third researcher (NCT). The selected articles were assessed using the Joanne Briggs Institute (JBI) checklist for prevalence studies. This tool was selected as a preliminary literature review reveals a preponderance of cross-sectional studies. The outcome of the assessment can be found in Table 1.
Each study will be assessed for quality with the JBI by two independent authors. Differences in grading were resolved by an arbitrator. The final grading of each article on each question is shown here. Y: Yes, N: No, U: Unclear, SFI: Seek Further Info.

Publication Bias
A search of the gray literature performed through WorldCat ® and Google Scholar did not yield any relevant unpublished work. Visualisation of funnel plot and Egger's regression test was also performed.

Data Synthesis
The full text of all included articles was analyzed by two researchers (PO and SYT). Key findings from the included studies were narratively synthesized. The following study characteristics were included: study location, study timing, study population, study design, survey instruments, reported outcomes, and limitations.

Data Analysis
Study characteristics and the outcome of interest were narratively summarized in tables. To facilitate our meta-analysis, the formula "vaccine hesitancy = 1 − vaccine acceptance" was used. The pooled prevalence of vaccine acceptance and hesitancy was performed using R statistical software version 4.3.1.

Results
A total of 1763 studies were identified through the search strategies of PubMed/MEDLINE, EMBASE, CINAHL, and Google Scholar. After excluding duplicates, 1074 articles remained. Titles and abstracts were screened, resulting in the exclusion of 1403 articles. The full text was sought and reviewed for 31 articles. There were 13 articles that satisfied the eligibility criteria and were included in this systematic review ( Figure 1). characteristics were included: study location, study timing, study population, stu sign, survey instruments, reported outcomes, and limitations.

Data Analysis
Study characteristics and the outcome of interest were narratively summar tables. To facilitate our meta-analysis, the formula "vaccine hesitancy = 1 − vacc ceptance" was used. The pooled prevalence of vaccine acceptance and hesitancy w formed using R statistical software version 4.3.1.

Results
A total of 1763 studies were identified through the search strategies of PubMed LINE, EMBASE, CINAHL, and Google Scholar. After excluding duplicates, 1074 remained. Titles and abstracts were screened, resulting in the exclusion of 1403 a The full text was sought and reviewed for 31 articles. There were 13 articles that s the eligibility criteria and were included in this systematic review ( Figure 1).

Study Characteristics
All the included studies, published up to 24 August 2022, assessed the inten adolescents to receive the COVID-19 vaccine and its associated factors, inc

Study Characteristics
All the included studies, published up to 24 August 2022, assessed the intention of adolescents to receive the COVID-19 vaccine and its associated factors, including attitudes, opinions, and perspectives. All the studies were cross-sectional, and adolescents were recruited either from existing databases or through convenience or snowball sampling through online outreach. The studies originated from various parts of the world, including Asia [37][38][39]41,42,46,47], the United States (US) [43][44][45], and Europe [35,36,40]. All studies employed questionnaires as study instruments.

Publication Bias
There was no significant funnel plot asymmetry; regression-based Egger's test for small-study effects did not indicate evidence of publication bias (p = 0.545) ( Figure 3).

Factors Influencing Intention to Vaccinate against COVID-19 in Adolescents [48]
Factors were classified according to a modified conceptual framework of factors influencing vaccine acceptance and hesitancy proposed by Joshi et al. [48]. The factors were first dichotomized into enablers (Table 3) and barriers (Table 4) before being subclassification into five broad categories. The categories included: "Socio-demographic determinants"; "Communication about COVID-19 pandemic and vaccination"; "COVID-19 vaccine & related issues"; "COVID-19 infection & related issues" and "other determinants".
Although the female gender was identified as a barrier to vaccine acceptance in Sweden [40] and China [42], multiple other studies [35,38,39,43,45,46] found no association, while Fazel et al. found that being female was instead an enabler to vaccine acceptance [36].

Communication about COVID-19 Pandemic and Vaccine Related Factors
Adolescents cited possessing information about vaccine safety [44] and wanting to follow governmental recommendations [35] as reasons to be vaccinated.

Publication Bias
There was no significant funnel plot asymmetry; regression-based Egger's test for small-study effects did not indicate evidence of publication bias (p = 0.545) (Figure 3).

Factors Influencing Intention to Vaccinate against COVID-19 in Adolescents [48]
Factors were classified according to a modified conceptual framework of factors influencing vaccine acceptance and hesitancy proposed by Joshi et al. [48]. The factors were first dichotomized into enablers (Table 3) and barriers (Table 4) before being subclassification into five broad categories. The categories included: "Socio-demographic determinants"; "Communication about COVID-19 pandemic and vaccination"; "COVID-19 vaccine & related issues"; "COVID-19 infection & related issues" and "other determinants".
Being less socially connected (in terms of increasing media usage and less identification with the school community) [36,45] also had a negative influence on their vaccination intention.

Discussion
Overall, the willingness to be vaccinated varies extensively across populations, but adolescents in most countries studied appeared to be receptive to COVID-19 vaccination.
Vaccine hesitancy rates (VHR) were lower in Asia, with the lowest rates in China [39,47]. Among Chinese studies, there was a reduction in VHR from 39.9% to as low as 5.7% relative to the period of data collection [39,42,47].
The main enablers of vaccine acceptance were confidence in vaccine effectiveness and safety; the desire to protect others and themselves; and parental acceptance of the COVID-19 vaccine. The result suggests that parental norms strongly influence the vaccination intention of adolescents, which is congruent with existing literature [50][51][52]. It emphasizes the need for strategies to target vaccine hesitancy in both parents and their children. Oka et al. noted that the main sources of information on COVID-19 vaccines for adolescents originated from family members [41]. Therefore, local frontline community healthcare professionals could also raise adolescents' and parents' awareness of their role in curbing the virus spread by disseminating evidence-based information on vaccine safety and effectiveness. Such personalized measures can assist in clearing their doubts and addressing these major concerns [53].
The main barriers to vaccine acceptance were concerns over vaccine safety and efficacy, concerns over long-term side effects, and a low perceived necessity. The adolescent concerns are consistent with current literature [7,54,55] and could stem from delayed approval of vaccines for adolescents [56]. Adolescents could also be more skeptical regarding vaccine effectiveness and safety due to the exaggerated information they encounter on social media [57][58][59]. Despite several randomized controlled trials proving the safety and effectiveness of the COVID-19 vaccine [4][5][6][60][61][62], such evidence might not have been conveyed to the public, especially adolescents, in lay terms that this target audience could comprehend. Hence, public health messages on vaccine safety should be packaged to catch the attention of adolescents or their parents and help them understand both the benefits and potential risks for informed decision-making.
The low perceived necessity of the COVID-19 vaccine among adolescents could result in low vaccine acceptance. Studies examining adolescent brain development suggest that their flawed risk perception may be due to their relatively underdeveloped prefrontal cortex as well as their decreased ability to anticipate future consequences [63][64][65][66]. While acknowledging that adolescents may not act in their best interests, it is important to provide them with the appropriate information and resources to make their own decisions.
This review had several limitations. First, only articles published in English were included. Articles from non-English-speaking countries may have been published in their native language; thus, adolescents from those countries may not be represented in this paper.
Secondly, most studies did not use validated instruments to record associated factors influencing vaccine acceptance. Although meta-analysis was performed, the high heterogeneity of the data limited the quality of the analysis. Employing validated instruments that are standardized across studies would facilitate the generation of higher-quality data.
Thirdly, a causal relationship between the intention to vaccinate and the identified factors could not be established due to the cross-sectional design of the included studies. There are likely multiple confounders influencing vaccine acceptance, and a randomized controlled trial could be conducted to definitively identify causative factors. However, it is impractical and impossible to conduct one as there are too many factors to control. Nonetheless, when adequately powered, cross-sectional studies are more practical and provide sufficient data.
Fourthly, the adolescent age group, ranging from 10 to 19 years, was selected based on the WHO definition. In many countries, adolescents aged 10 to 17 years are considered children and require parental consent for vaccination, while adolescents aged 18 to 19 years are considered adults and can act based on their own opinions. This difference in perspective was not accounted for, as the included studies only performed analyses on the whole population with no subgroup analyses. Future studies could target only younger adolescents or perform subgroup analyses in studies with older adolescents.
Finally, each country had differing COVID-19 vaccine approval and procurement timelines. The varied rollout among adolescents potentially affected their views and intentions to vaccinate. Vaccine type and brand were also rarely mentioned as potential confounding factors. These logistical considerations could be further explored in prospective research to determine if they play a significant role in influencing vaccine acceptance.
Nevertheless, this is the first systematic review to examine COVID-19 vaccine acceptance rates and associated reasons for vaccine uptake among adolescents. This review only included papers that reported the adolescent's perspective and excluded those that examined parental vaccine hesitancy. Both quantitative and qualitative outcomes were reported, facilitating a deeper understanding of the adolescent thought process behind their intention to vaccinate.
Future research should conform to the SAGE working group definition of vaccine hesitancy and utilize validated instruments. Reduced heterogeneity will facilitate the conduct of future meta-analyses to better evaluate the intention to vaccinate and the associated factors.

Conclusions
This systematic review adds evidence on the prevalence, enablers, and barriers that influence vaccination intention in the adolescent population. The pooled prevalence of COVID-19 vaccine acceptance among adolescents was 63% (95% CI: 52-73%). Concerns about vaccine safety and effectiveness remain a major concern, which should be adequately addressed to expedite vaccine uptake. Generating peer norms and obtaining parental concordance are ways to enhance vaccination intention among adolescents.

Conflicts of Interest:
The authors declare no conflict of interest.