Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Children and Adolescents: A Systematic Review

Abstract

Aim: To identify the safety, immunogenicity, and protective efficacy of COVID-19 vaccines in children and adolescents. Methods: We conducted a systematic review of published studies and ongoing clinical studies related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents (aged < 18 years). Databases including PubMed, Web of Science, WHO COVID-19 database, and China National Knowledge Infrastructure (CNKI) were searched on 23 July 2021. International Clinical Trials Registry Platform (ICTRP) was also searched to identify ongoing studies. Results: Eight published studies with a total of 2852 children and adolescents and 28 ongoing clinical studies were included. Of the eight published studies, two were RCTs, two case series, and four case reports. The investigated COVID-19 vaccines had good safety profiles in children and adolescents. Injection site pain, fatigue, headache, and chest pain were the most common adverse events. A limited number of cases of myocarditis and pericarditis were reported. The RCTs showed that the immune response to BNT162b2 in adolescents aged 12–15 years was non-inferior to that in young people aged 16–25 years, while with 3 μg CoronaVac injection the immune response was stronger than with 1.5 μg. The efficacy of BNT162b2 was 100% (95% CI: 75.3 to 100), based on one RCT. Of the 28 ongoing clinical studies, twenty-three were interventional studies. The interventional studies were being conducted in fifteen countries, among them, China (10, 43.5%) and United States(9, 39.1%) had the highest number of ongoing trials. BNT162b2 was the most commonly studied vaccine in the ongoing trials. Conclusion: Two COVID-19 vaccines have potential protective effects in children and adolescents, but awareness is needed to monitor possible adverse effects after injection. Clinical studies of the COVID-19 vaccination in children and adolescents with longer follow-up time, larger sample size, and a greater variety of vaccines are still urgently needed.

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Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	Field Sample Permit: 2.2 Search strategy: We systematically searched databases including Medline (via PubMed), Web of Science, World Health Organization (WHO) COVID-19 database, and China National Knowledge Infrastructure (CNKI), from their inception to 23 July 2021 to find out original studies related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents.
Sex as a biological variable	2.4 Data extraction: The following data was extracted from the original studies: 1) basic information: publication date, country, study design, name of vaccine; 2) participants information: age, sample size, female/male number; and 3) outcome information: safety, immunogenicity, and efficacy of COVID-19.
Randomization	The study design was limited to primary studies, including randomized clinical trials (RCTs), non-RCTs or observational studies.
Blinding	not detected.
Power Analysis	not detected.

Table 2: Resources

Software and Algorithms
Sentences	Resources
In addition, the Cochrane Handbook for Systematic Reviews of Interventions was followed to develop this systematic review [14].	Cochrane Handbook suggested: None
2.2 Search strategy: We systematically searched databases including Medline (via PubMed), Web of Science, World Health Organization (WHO) COVID-19 database, and China National Knowledge Infrastructure (CNKI), from their inception to 23 July 2021 to find out original studies related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents.	PubMed suggested: (PubMed, RRID:SCR_004846)
We first developed a search strategy for Medline after several attempts, and the search strategies for the other databases were then adapted from Medline.	Medline suggested: (MEDLINE, RRID:SCR_002185)
We also searched Google Scholar and reference lists of identified articles to avoid missing important literature.	Google Scholar suggested: (Google Scholar, RRID:SCR_008878)
We used Endnote 20.0.1 in the whole screening process.	Endnote suggested: (EndNote, RRID:SCR_014001)
The meta-analyses are planned to be performed in RevMan 5.4.1 (The Cochrane Collaboration, 2020.) and Stata/SE 15.1 (Copyright 1985-2017 StataCorp LLC) software.	RevMan suggested: (RevMan, RRID:SCR_003581) Cochrane Collaboration suggested: None StataCorp suggested: (Stata, RRID:SCR_012763)
Microsoft Excel 16.51 (2019) was used for data processing and analysis.	Microsoft Excel suggested: (Microsoft Excel, RRID:SCR_016137)
Adobe Illustrator will be used to map ongoing clinical trials of COVID-19 vaccine in children or adolescents worldwide.	Adobe Illustrator suggested: (Adobe Illustrator, RRID:SCR_010279)

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

Our study showed that some vaccines have now been developed in pediatric populations with associated RCTs and proven protective efficacy and safety, however, these two studies both have limitations on small sample size and lack of long-term safety and immunogenicity data, for example, myocarditis and pericarditis should be closely monitored. Most cases of myocarditis and pericarditis associated with the COVID-19 vaccine were mild and mostly in males. According to Washington State Department of Health data on immunization, Schauer et al. [26] estimated a possible incidence of 0.008% in adolescents 16-17 years of age and 0.01% in those 12 through 15 years of age following the second dose. Another population to consider for vaccination of children and adolescents is multisystemic inflammatory syndrome (MIS). In April 2020, children with presentations similar to incomplete Kawasaki disease (KD) or toxic shock syndrome were documented in reports from the UK [31]. Since then, such children have been reported in other parts of the world [32-34]. This is termed multisystemic inflammatory syndrome in children (MIS-C). Study showed that the pooled proportions of MIS-C in Hispanic and Black cases were 34.6% (95% CI, 28.3–40.9) and 31.5% (95% CI, 24.8–38.1), respectively [35]. The overall mortality of MIS-C is approximately 1–2% [36]. Our review did not involve the children with MIS-C. Therefore, it is unclear whether children with SARS-CoV-2 infection complicated by multisystemic inflam...

Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

Identifier	Status	Title
NCT04816643	Recruiting	Study to Evaluate the Safety, Tolerability, and Immunogenici…
NCT04796896	Recruiting	A Study to Evaluate Safety and Effectiveness of mRNA-1273 CO…
NCT04299724	Recruiting	Safety and Immunity of Covid-19 aAPC Vaccine
NCT04276896	Recruiting	Immunity and Safety of Covid-19 Synthetic Minigene Vaccine

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

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Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Children and Adolescents: A Systematic Review

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