Background
The ongoing global battle against the coronavirus disease 2019 (COVID-19) pandemic has seen remarkable progress in vaccine development and distribution. Reference Sharif, Alzahrani, Ahmed and Dey1,Reference Zheng, Shao, Chen, Zhang, Wang and Zhang2 As adults and high-risk populations receive their COVID-19 vaccinations, the focus has increasingly turned toward vaccinating children and adolescents. While much attention has rightfully been placed on preventing COVID-19 infections in these age groups, it is equally critical to consider the potential impact of vaccination on preventing post-COVID conditions, often referred to as long COVID.
Post-COVID conditions encompass a wide spectrum of persistent health problems that can afflict individuals for weeks, months, or even longer after the initial COVID-19 infection. 3 According to a published systematic literature review, the prevalence of post-COVID conditions in the pediatric population varies remarkably from 1.6% to 70%. Reference Pellegrino, Chiappini, Licari, Galli and Marseglia4 Long COVID can negatively affect daily function and school attendance. 3,Reference Pellegrino, Chiappini, Licari, Galli and Marseglia4
Research has demonstrated the efficacy, safety, and tolerability of COVID-19 vaccines in the pediatric population. Reference Principi and Esposito5 Beyond preventing infection, COVID-19 vaccines also can prevent severe outcomes, including emergency department or urgent care visits, hospitalizations, and even death. Reference Oliver, Wallace and Link-Gelles6,Reference Shiri, Evans and Talarico7 Furthermore, vaccination can allow more children to attend school. Reference Principi and Esposito5
As COVID-19 vaccine campaigns have progressed, more children are getting vaccinated. Vaccine effectiveness (VE) assesses the level of protection provided by COVID-19 vaccines against specific conditions. Reference Zheng, Shao, Chen, Zhang, Wang and Zhang2 While VE against post-COVID conditions among the adult population is estimated to be 30%, Reference Marra, Kobayashi and Callado8 VE against post-COVID conditions among the pediatric population is still unknown. Therefore, our objective was to conduct a systematic literature review on the effectiveness of COVID-19 vaccines to prevent post-COVID conditions in children and adolescents, and we pooled the results of published studies to allow for more precise effectiveness estimates.
Methods
Systematic literature review and inclusion and exclusion criteria
This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement Reference Moher, Liberati, Tetzlaff and Altman9 and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines Reference Stroup, Berlin and Morton10 and was registered on Prospero (https://www.crd.york.ac.uk/PROSPERO/) on June 9, 2023 (registration number CRD42023456888). Institutional Review Board approval was not required. Inclusion criteria for studies in this systematic review were as follows: original research manuscripts, published in peer-reviewed scientific journals, involved vaccinated (at least 1 dose of COVID-19 vaccines [mRNA or vectorial or inactivated viral vaccine]) and unvaccinated individuals, evaluated the long-term effectiveness of the COVID-19 vaccine, evaluated the pediatric population (individuals < 21 years old), and observational study design. Post-COVID condition (also known as long COVID) was defined as a wide range of health symptoms that are present 4 or more weeks after COVID-19 infection. 3 The literature search included studies from December 1, 2019, to August 14, 2023. Editorials, commentaries, reviews, study protocols, and studies in the adult population were excluded. Studies without a comparison between vaccinated and unvaccinated individuals (or other vaccinated control groups) were also excluded.
Search strategy
We performed literature searches in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase (Elsevier Platform), Cochrane Central Register of Controlled Trials, Scopus (which includes EMBASE abstracts), and Web of Science. The entire search strategy is described in Supplementary Appendix 1. After applying the exclusion criteria, we reviewed 30 articles, of which 8 met the inclusion criteria and were included in the systematic literature review (Figure 1).
Figure 1. Literature search for articles on the COVID-19 vaccine effectiveness in post-COVID conditions.
Data abstraction and quality assessment
Titles and abstracts of all articles were screened to assess whether they met the inclusion criteria. Abstract screening was performed by 2 reviewers (MCG and ARM). Of 7 independent reviewers (ARM, GYC, IP, MCG, MKH, TK, and VL), 2 independently abstracted data for each article using a standardized abstraction form. Reviewers resolved disagreements by consensus.
The reviewers abstracted data on study design, population and location, study period (months) and calendar time, demographic and characteristics of participants, and the types of COVID-19 vaccine administered if available. Post-COVID conditions were considered the primary outcome to calculate VE after at least 1 dose of a COVID-19 vaccine. Eight corresponding authors were contacted for additional information, and 2 were able to provide additional information regarding the number of individuals with and without post-COVID conditions in both vaccinated and unvaccinated groups. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12 The risk of bias was assessed using the Downs and Black scale. Reference Downs and Black13 Reviewers answered all original questions from this scale except for question #27 (a single item on the Power subscale scored 0 to 5), which was changed to a yes or no. Two authors performed component quality analysis independently, reviewed all inconsistent assessments, and resolved disagreements by consensus. Reference Alderson, Green and Higgins14
Statistical analysis
To perform a meta-analysis on the extracted data, we calculated the pooled diagnostic odds ratio (DOR) for post-COVID conditions between vaccinated (received at least 1 dose of a COVID-19 vaccine) and unvaccinated individuals. We performed stratified analyses by the timing of the COVID-19 vaccine (ie, those with COVID-19 vaccines before or after COVID-19 diagnosis and those with COVID-19 vaccines before COVID-19 diagnosis) and between those vaccinated with 2 doses and unvaccinated individuals. We performed statistical analysis using R version 4.1.0 with mada package version 0.5.8. Reference Doebler, Holling and Sousa-Pinto15 Analogous to the meta-analysis of the odds ratio methods for the DOR, an estimator of random-effects model following the approach of DerSimonian and Laird is provided by the mada package. Reference Doebler, Holling and Sousa-Pinto15 For our meta-analysis, we used a bivariate random-effects model, adopting a similar concept of performing the diagnostic accuracy. This enabled simultaneous pooling of sensitivity and specificity with mixed-effect linear modeling while allowing for the trade-off between them. Reference Reitsma, Glas, Rutjes, Scholten, Bossuyt and Zwinderman16,Reference Goto, Ohl, Schweizer and Perencevich17 Heterogeneity between studies was evaluated with I2 estimation and the Cochran Q statistic test. Publication bias was assessed using the Egger test with R version 4.1.0 with metafor package. Reference Viechtbauer18
Results
Characteristics of included studies
Eight studies met the inclusion criteria Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Morello, Mariani and Mastrantoni24 and were included in the final review (Table 1). All studies were non-randomized; Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Morello, Mariani and Mastrantoni24 of these, 5 were prospective cohort studies, Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Ertesvåg, Iversen and Blomberg21–Reference Morello, Mariani and Mastrantoni24 2 were cross-sectional studies, Reference Adler, Israel and Yehoshua19,Reference Atchison, Whitaker and Donnelly20 and 1 was a retrospective cohort study. Reference Pinto Pereira, Nugawela and Rojas11 Four of these studies evaluated the Pfizer/BioNTech vaccine. Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Ertesvåg, Iversen and Blomberg21,Reference Jarupan, Jantarabenjakul and Jaruampornpan22,Reference Morello, Mariani and Mastrantoni24 Two analyzed the Moderna vaccine, Reference Ertesvåg, Iversen and Blomberg21,Reference Morello, Mariani and Mastrantoni24 1 analyzed the AstraZeneca vaccine, Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12 and 1 analyzed the Sinopharm vaccine. Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12 Four studies did not report the type of COVID-19 vaccine administered. Reference Pinto Pereira, Nugawela and Rojas11,Reference Adler, Israel and Yehoshua19,Reference Atchison, Whitaker and Donnelly20,Reference Messiah, Hao and DeSantis23 There were no published studies that evaluated post-COVID conditions as an outcome of bivalent COVID-19 vaccines.
Table 1. Summary of characteristics of studies included in the systematic literature review
Note. COVID-19, coronavirus disease 2019; D&B score, Downs and Black score; NR, not reported; PCR, polymerase chain reaction.
* Long duration of COVID-19 symptoms 4-12 weeks.
** Long duration of COVID-19 symptoms ≥12 week.
Two studies included in our review were conducted in the United Kingdom, Reference Pinto Pereira, Nugawela and Rojas11,Reference Atchison, Whitaker and Donnelly20 and 2 were conducted in Thailand. Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Jarupan, Jantarabenjakul and Jaruampornpan22 One study each was performed in Israel, Reference Adler, Israel and Yehoshua19 Italy, Reference Morello, Mariani and Mastrantoni24 Norway, Reference Ertesvåg, Iversen and Blomberg21 and the United States. Reference Messiah, Hao and DeSantis23 All studies were performed between February 2020 and October 2022. The study duration varied from 2 months to 34 months. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Morello, Mariani and Mastrantoni24
In our qualitative analysis, 8 studies including 23,995 children and adolescents evaluated the effect of vaccination among vaccinated and unvaccinated pediatric individuals on post-COVID conditions. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Morello, Mariani and Mastrantoni24 Four studies evaluated VE in pediatric individuals vaccinated only before COVID-19 infection, Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Ertesvåg, Iversen and Blomberg21,Reference Morello, Mariani and Mastrantoni24 1 study evaluated VE for post-COVID conditions among those who were vaccinated after COVID-19 infection, Reference Jarupan, Jantarabenjakul and Jaruampornpan22 and 3 studies evaluated VE but did not specify the timing of the vaccine. Reference Pinto Pereira, Nugawela and Rojas11,Reference Adler, Israel and Yehoshua19,Reference Messiah, Hao and DeSantis23 All 8 studies evaluated VE with at least 1 dose of a COVID-19 vaccine. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Morello, Mariani and Mastrantoni24 Two studies evaluated vaccinated children and adolescents with 2 doses of vaccine. Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Morello, Mariani and Mastrantoni24 While 5 of 8 studies reported data during the Omicron variant era, Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20–Reference Jarupan, Jantarabenjakul and Jaruampornpan22,Reference Morello, Mariani and Mastrantoni24 3 studies took place before the Omicron variant era. Reference Pinto Pereira, Nugawela and Rojas11,Reference Adler, Israel and Yehoshua19,Reference Messiah, Hao and DeSantis23
Each study adopted different definitions for post-COVID conditions (Table 1). Post-COVID conditions were defined as symptoms lasting more than 4 weeks in 2 studies, Reference Adler, Israel and Yehoshua19,Reference Messiah, Hao and DeSantis23 more than 12 weeks in 5 studies, Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20–Reference Jarupan, Jantarabenjakul and Jaruampornpan22,Reference Morello, Mariani and Mastrantoni24 and more than 6 months in 1 study. Reference Pinto Pereira, Nugawela and Rojas11 All studies used at least one of the common post-COVID condition symptoms (details shown in Table 1) to make a diagnosis of a post-COVID condition. Six of the included studies did not show any benefit of COVID-19 vaccination in reducing post-COVID condition symptoms in children and adolescents. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Ertesvåg, Iversen and Blomberg21,Reference Morello, Mariani and Mastrantoni24 One study showed that vaccination was protective against post-COVID-19 symptoms, Reference Messiah, Hao and DeSantis23 and 1 study did not report the benefit of COVID-19 vaccination. Reference Jarupan, Jantarabenjakul and Jaruampornpan22
In total, 5 studies, comprising 20,325 children and adolescents, investigated post-COVID conditions among individuals who had received at least 1 dose of the COVID-19 vaccine either before or after COVID-19 infection. These studies were subsequently included in the meta-analysis (Figure 2). Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 The prevalence of children and adolescents who did not receive COVID-19 vaccines ranges from 65% to 97%. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 The pooled prevalence of post-COVID conditions was 21.3% among those who were unvaccinated and 20.3% among those who received at least 1 dose. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 The pooled DOR for post-COVID-19 conditions among the pediatric population vaccinated with at least 1 dose was 1.07 (95% CI, 0.77–1.49). Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 Of the 5 studies, 3 evaluated post-COVID conditions in individuals who received the COVID-19 vaccine before infection (Supplementary Appendix 2). Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Morello, Mariani and Mastrantoni24 The DOR was 1.23 (95% CI, 0.84–1.80). Reference Pinto Pereira, Nugawela and Rojas11,Reference Adler, Israel and Yehoshua19,Reference Messiah, Hao and DeSantis23 Two studies assessed post-COVID conditions for those who received 2 doses before infection (Supplementary Appendix 3). Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Morello, Mariani and Mastrantoni24 The DOR was 0.82 (95% CI, 0.63–1.08) Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Morello, Mariani and Mastrantoni24 (Table 2). Because there were no studies evaluating post-COVID conditions for those who received at least 1 dose of each specific type of COVID-19 vaccine (mRNA or viral vector or inactivated viral vaccine), we did not perform a stratified analysis. The results of meta-analyses were homogeneous for studies evaluating post-COVID conditions in individuals who received the COVID-19 vaccine before or after COVID-19 infection (heterogeneity P = .38, I2 = 5%), and homogenous for studies evaluating post-COVID conditions in individuals receiving vaccine only before infection (heterogeneity P = .26, I2 = 25%), and also homogenous for studies evaluating post-COVID conditions in children who received 2 doses (heterogeneity P = .77, I2 = 0%), respectively. There was no evidence for publication bias among the 5 studies included in the meta-analysis (P = .93).
Figure 2. Forest plot of COVID-19 vaccine effectiveness among post-COVID-19 conditions in individuals who received at least 1 dose of COVID-19 vaccine before or after COVID-19 infection. Diagnostic odds ratios (DOR) were determined with the DerSimonian and Laird random-effects method. Note: CI, confidence interval.
Table 2. Subset analyses evaluating COVID-19 vaccine effectiveness against post-COVID conditions in individuals who received COVID-19 vaccine before or after COVID-19 infection
Note. COVID-19, coronavirus disease 2019; CI, confidence interval.
One dose – before /after COVID-19 infection: 5 studies (Atchison 2023, Lokanuwatsatien 2023, Messiah 2022, Morello 2023, Pinto Pereira 2023).
One dose – before COVID-19 infection: 3 studies (Atchison 2023, Lokanuwatsatien 2023, Morello 2023).
Two doses – before COVID-19 infection: 2 studies (Lokanuwatsatien 2023, Morello 2023).
Regarding the quality assessment scores of the 8 included studies, the great majority of the studies (6 studies) were considered good quality (19–23 of 28 possible points) Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Ertesvåg, Iversen and Blomberg21,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 per the Downs and Black quality tool, and 2 studies were considered fair (14–18 points). Reference Pinto Pereira, Nugawela and Rojas11,Reference Jarupan, Jantarabenjakul and Jaruampornpan22
Discussion
Our systematic literature review and meta-analysis aimed to assess the VE of COVID-19 vaccination in mitigating post-COVID conditions in children and adolescents. The prevalence of those who did not receive COVID-19 vaccines was high, ranging from 65% to 97%. The pooled prevalence of post-COVID conditions was similar between unvaccinated (21.3%) and those who received at least 1 dose (20.3%). Reference Stroup, Berlin and Morton10,Reference Pinto Pereira, Nugawela and Rojas11,Reference Adler, Israel and Yehoshua19,Reference Jarupan, Jantarabenjakul and Jaruampornpan22,Reference Messiah, Hao and DeSantis23 This meta-analysis did not demonstrate statistically significant protection with COVID-19 vaccination against post-COVID conditions in the pediatric population. Given the limited number of studies included in this meta-analysis, each with different criteria for defining post-COVID conditions, further research is necessary to comprehensively assess VE.
The pursuit of effective vaccination strategies against COVID-19, particularly for children and adolescents, has been a crucial aspect of the global response to the pandemic. Reference Sharif, Alzahrani, Ahmed and Dey1,Reference Shiri, Evans and Talarico7,Reference Rosenberg, Sawhney, Bernstein and Romero25 The low prevalence of COVID-19 vaccination among the pediatric population is a concerning issue that warrants further examination. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 Initially, COVID-19 vaccines were primarily authorized for adults, and the distribution to children and adolescents occurred later. Reference Rosenberg, Sawhney, Bernstein and Romero25 Certainly, understanding parental hesitancy regarding COVID-19 vaccination for their children and adolescents is a critical aspect to consider in the context of this study. Reference Byrne, Thompson, Filipp and Ryan26 Additionally, acknowledging that the pediatric population was one of the last to receive COVID-19 vaccines adds complexity to the discussion. The delayed access of children and adolescents to COVID-19 vaccines might have contributed to a sense of uncertainty among parents. They may have been waiting for more data and real-world evidence of vaccine safety and efficacy in this age group before making decisions. Reference Khemiri, Ayouni, Triki and Haddad-Boubaker27 The spread of misinformation and disinformation about COVID-19 vaccines has contributed to vaccine hesitancy in both adults and children. Reference Byrne, Thompson, Filipp and Ryan26 False claims about vaccine safety, efficacy, and adverse events can lead parents to make uninformed decisions about vaccinating their children. Reference Byrne, Thompson, Filipp and Ryan26 Highlighting the potential risks of post-COVID conditions in adult populations can be a persuasive argument for vaccination. Reference Trapani, Verlato and Bertino28 Parents may be more inclined to vaccinate their children if they understand the potential long-term health consequences of a COVID-19 infection, even if it is mild. Reference Pellegrino, Chiappini, Licari, Galli and Marseglia4,Reference Trapani, Verlato and Bertino28 Moreover, the study’s focus on pediatric populations highlights the need for age-specific considerations in vaccination campaigns. Reference Shiri, Evans and Talarico7,Reference Rosenberg, Sawhney, Bernstein and Romero25,Reference Creech, Anderson and Berthaud29
The observed wide variation in the prevalence of post-COVID conditions in pediatric populations, ranging from 1.6% to 70%, underscores the complexity of this issue, Reference Pellegrino, Chiappini, Licari, Galli and Marseglia4 possibly influenced by an individual’s age, health conditions, and viral variants problems. Reference Trapani, Verlato and Bertino28,Reference Groff, Sun and Ssentongo30 Our previous systematic review and meta-analysis evaluating the VE against post-COVID conditions among fully vaccinated adults revealed that the pooled prevalence of post-COVID conditions was 11.8% among those who were unvaccinated and 5.3% among those individuals who were fully vaccinated. Reference Marra, Kobayashi and Callado8 This present systematic review demonstrated that the pediatric population had a higher prevalence at 21% in unvaccinated and 20% in vaccinated pediatric patients. The higher prevalence of post-COVID conditions in pediatric populations compared with adults is a matter of concern and requires careful consideration. Several factors could contribute to this difference. Reference Rosenberg, Sawhney, Bernstein and Romero25,Reference Groff, Sun and Ssentongo30,Reference Bygdell, Kindblom, Martikainen, Li and Nyberg31 Emerging variants could potentially have different effects on post-COVID conditions, and their prevalence may influence VE. Reference Marra, Sampaio and Ozahata32 Prior research indicated that the Delta and Omicron variants led to fewer systemic inflammatory responses, severe illnesses, or fatalities, thereby resulting in milder long COVID symptoms compared with the original wild-type variant (Wuhan). Reference Fernández-de-las-Peñas, Cancela-Cilleruelo and Rodríguez-Jiménez33,Reference Antonelli, Pujol, Spector, Ourselin and Steves34 In addition, it has been reported that the prevalence of post-COVID conditions was lower during the Omicron era than during other strains, and the prior systematic review among adults might have included more research that covered the additional newer variants. Reference Antonelli, Pujol, Spector, Ourselin and Steves34,Reference Fernández-de-las-Peñas, Rodríguez-Jiménez and Cancela-Cilleruelo35 The variability in how post-COVID conditions were defined across the included studies poses a significant limitation for understanding this issue. Different studies used different time thresholds (4 weeks, 12 weeks, 6 months) to define post-COVID conditions. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Morello, Mariani and Mastrantoni24 This heterogeneity in definitions makes it challenging to compare results across studies and draw firm conclusions about the prevalence and impact of these conditions.
While our previous meta-analysis among the adult population suggested that COVID-19 vaccines might effectively prevent post-COVID-19 conditions, Reference Marra, Kobayashi and Suzuki36 the present meta-analysis did not demonstrate any protective effect. There are a few potential reasons for this discrepancy. Children and adolescents have unique physiological and immunological characteristics, which may influence vaccine responses and the risk of post-COVID conditions. Reference Rosenberg, Sawhney, Bernstein and Romero25 It is worth noting that there have been previous studies that have also shown limited effectiveness of vaccines in preventing post-COVID conditions. Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Morello, Mariani and Mastrantoni24 These findings suggest that the relationship between vaccination and post-COVID outcomes is complex and may vary across different age groups and populations. Moreover, the timing of vaccination concerning the COVID-19 infection may be a contributing factor. Some studies have analyzed VE when administered before COVID-19 infection, Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20 while others have assessed outcomes when given after infection. Reference Pinto Pereira, Nugawela and Rojas11,Reference Jarupan, Jantarabenjakul and Jaruampornpan22 These differences in timing may contribute to the divergent results observed in different studies. Consequently, ongoing research and monitoring of vaccine safety and effectiveness in these age groups are essential for refining vaccination strategies.
Our study had several limitations. First, there were a relatively small number of articles that met the inclusion criteria. With only 8 studies included in the systematic literature review, Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Adler, Israel and Yehoshua19–Reference Morello, Mariani and Mastrantoni24 the available evidence may not represent the full spectrum of the pediatric population’s experience with post-COVID conditions. All of the included studies in the meta-analysis investigating the VE in preventing post-COVID conditions employ non-randomized and different observational study designs, Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Atchison, Whitaker and Donnelly20,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 including cohort studies Reference Pinto Pereira, Nugawela and Rojas11,Reference Lokanuwatsatien, Satdhabudha and Tangsathapornpong12,Reference Messiah, Hao and DeSantis23,Reference Morello, Mariani and Mastrantoni24 and a cross-sectional study. Reference Atchison, Whitaker and Donnelly20 While the authors applied rigorous quality assessment criteria, the possibility of residual confounding factors and selection of bias that were not accounted for in the original studies remains. Additionally, it’s important to consider that children and adolescents who were sicker, frailer, or at higher risk might have been more inclined to receive vaccinations. This potential bias is difficult to completely account for in observational studies. Second, the articles included in this systematic literature review assessed the effectiveness of various COVID-19 vaccines, including mRNA vaccines, vector vaccines, and inactivated viral vaccines. The effectiveness of these vaccines in preventing post-COVID conditions may differ, but the analysis did not stratify results by vaccine type due to data limitations. Future research should explore potential differences in the impact of different vaccine types on post-COVID outcomes. Third, the studies included in our systematic literature review were conducted in various countries, with differing healthcare systems, demographics, COVID-19 vaccination programs, and COVID-19 prevalence. The diversity in settings could affect the generalizability of the findings to other regions or populations. It is important to consider that the impact of vaccines on post-COVID conditions may vary in different contexts. Reference Groff, Sun and Ssentongo30,Reference Marra, Kobayashi and Suzuki36 Lastly, although no evidence of publication bias was found in the meta-analysis, the potential for publication bias always exists in systematic reviews. Studies with significant findings, whether positive or negative, may be more likely to be published, potentially skewing the overall assessment of VE.
In conclusion, it appears that the pediatric population may experience a higher incidence of post-COVID conditions compared with adults. The study observed that COVID-19 vaccination, whether administered before or after a COVID-19 infection, did not reduce the occurrence of post-COVID conditions associated with the circulating variants during the study period among pediatric individuals. While this article contributes to our understanding of COVID-19 VE in preventing post-COVID conditions in the pediatric population, it is crucial to acknowledge the limitations of this study. Addressing these limitations through more extensive, standardized, and regionally diverse research, along with ongoing monitoring and robust study designs, will offer a more accurate insight into the relationship between vaccination and post-COVID outcomes in children and adolescents. Such efforts are vital for refining public health strategies and mitigating the long-term health effects of the pandemic among younger populations.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ash.2024.42.
Acknowledgments
We thank Jennifer Deberg, MLS, from the Hardin Library for the Health Sciences, University of Iowa Libraries, for assistance with the search methods.
Financial support
This study was not funded.
Competing interests
All authors report no conflict of interest relevant to this article.
Open access
