Impact of COVID-19 vaccination on the risk of long COVID: An umbrella review of meta-analyses
Keywords:
COVID-19 Vaccines, Post-Acute COVID-19 Syndrome, Vaccination , Meta-Analysis as Topic , Systematic Reviews as TopicAbstract
Background: Long COVID (post-acute COVID-19 syndrome) imposes a substantial burden on function, quality of life, and health services. Emerging evidence suggests COVID-19 vaccination may mitigate long-COVID risk, but estimates vary across syntheses and populations.
Objectives: To evaluate the impact of COVID-19 vaccination on the risk of long COVID by consolidating evidence from systematic reviews/meta-analyses, assessing methodological quality, and quantifying primary-study overlap.
Methods: We conducted an umbrella review of systematic reviews/meta-analyses indexed in PubMed, Scopus, and Web of Science (Dec 1, 2019–Sep 1, 2025; English). Eligibility followed PICOS; only SRs/MAs were included. Two reviewers screened, extracted data, and appraised quality with AMSTAR-2. Overlap of primary studies was quantified using the corrected covered area (CCA). Visual syntheses (AMSTAR-2 bubble plot; overlap matrix) were generated in RStudio (v4.3.1, ggplot2). Protocol registered on OSF.
Results: Five meta-analyses met inclusion criteria. Across adult populations, vaccination was consistently associated with reduced long-COVID risk, with pooled vaccine effectiveness (VE) commonly ~29–41% for primary series. Timing and dose mattered: protection was stronger when vaccinated before infection, and booster doses yielded the largest effects (VE ~70%). Pediatric evidence was inconclusive, with pooled estimates not reaching statistical significance. AMSTAR-2 ratings were High (2 reviews), Moderate (2), and Low (1, pediatric). CCA indicated moderate overlap across reviews, suggesting that portions of the apparent consistency derive from shared primary cohorts.
Conclusions: COVID-19 vaccination reduces the incidence of long COVID in adults, particularly when a complete primary series and booster doses are received prior to infection. Evidence in children/adolescents remains limited and non-definitive. Policymakers should prioritize completion of primary series and boosters as part of long-COVID prevention, while future research should standardize outcomes, extend follow-up, compare platforms/boosting schedules, and strengthen pediatric data.
References
1. Staffolani S, Iencinella V, Cimatti M, et al. Long COVID-19 syndrome as a fourth phase of SARS-CoV-2 infection. Infez Med. 2022;30(1):22-9. doi:10.53854/liim-3001-3
2. Caliman-Sturdza OA, Gheorghita R, Lobiuc A. Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches. Life (Basel). 2025;15(3):439. doi:10.3390/life15030439
3. Ambalavanan R, Snead RS, Marczika J, et al. Advancing the Management of Long COVID by Integrating into Health Informatics Domain: Current and Future Perspectives. Int J Environ Res Public Health. 2023;20(19):6836. doi:10.3390/ijerph20196836
4. Huh K, Kim YE, Bae GH, et al. Vaccination and the risk of post-acute sequelae after COVID-19 in the Omicron-predominant period. Clin Microbiol Infect. 2024;30(5):666-73. doi:10.1016/j.cmi.2024.01.028
5. Madenbayeva AM, Kurmangaliyeva SS, Urazayeva ST, et al. Impact of QazVac vaccination on clinical manifestations and immune responses in post-COVID syndrome: a cross-sectional study. Front Med (Lausanne). 2025;12:1556623. doi:10.3389/fmed.2025.1556623
6. Maier HE, Kowalski-Dobson T, Eckard A, et al. Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults. Open Forum Infect Dis. 2024;11(2):ofae039. doi:10.1093/ofid/ofae039
7. Kurmangaliyeva SS, Madenbayeva AM, Urazayeva ST, et al. A bibliometric analysis of the impact of COVID-19 vaccines on the immune system (2020-2024). Acta Biomed. 2025;96(3):17035. doi:10.23750/abm.v96i3.17035
8. Franchi M, Pellegrini G, Cereda D, et al. Natural and vaccine-induced immunity are equivalent for the protection against SARS-CoV-2 infection. J Infect Public Health. 2023;16(8):1137-41. doi:10.1016/j.jiph.2023.05.018
9. Notarbartolo S. T-Cell Immune Responses to SARS-CoV-2 Infection and Vaccination. Vaccines (Basel). 2024;12(10):1126. doi:10.3390/vaccines12101126
10. Kurmangaliyeva SS, Madenbayeva AM, Urazayeva ST, et al. The Role of Memory T-Cell Mediated Immunity in Long-term COVID-19: Effects of Vaccination Status. Iran J Med Sci. 2025;50(2):61-8. doi:10.30476/ijms.2024.104003.3744
11. Laupeze B, Del Giudice G, Doherty MT, et al. Vaccination as a preventative measure contributing to immune fitness. NPJ Vaccines. 2021;6(1):93. doi:10.1038/s41541-021-00354-z
12. Ghildiyal T, Rai N, Mishra Rawat J, et al. Challenges in Emerging Vaccines and Future Promising Candidates against SARS-CoV-2 Variants. J Immunol Res. 2024;2024:9125398. doi:10.1155/2024/9125398
13. Violan C, Quirant-Sanchez B, Palau-Antoja M, et al. Immune Durability and Breakthrough Infections 15 Months After SARS-CoV-2 Boosters in People over 65: The IMMERSION Study. Vaccines (Basel). 2025;13(7):738. doi:10.3390/vaccines13070738
14. Peine C, Stoliaroff-Pepin A, Reinacher U, et al. Effectiveness of COVID-19 vaccines against post-COVID-19 condition/long COVID: systematic review and meta-analysis. Clin Microbiol Infect. 2025. doi:10.1016/j.cmi.2025.07.026
15. Fusar-Poli P, Radua J. Ten simple rules for conducting umbrella reviews. Evid Based Ment Health. 2018;21(3):95-100. doi:10.1136/ebmental-2018-300014
16. Gao P, Liu J, Liu M. Effect of COVID-19 Vaccines on Reducing the Risk of Long COVID in the Real World: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022;19(19):12422. doi:10.3390/ijerph191912422
17. Gutfreund MC, Kobayashi T, Callado GY, et al. The effectiveness of the COVID-19 vaccines in the prevention of post-COVID conditions in children and adolescents: a systematic literature review and meta-analysis. Antimicrob Steward Healthc Epidemiol. 2024;4(1):e54. doi:10.1017/ash.2024.42
18. Marra AR, Kobayashi T, Callado GY, et al. The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research. Antimicrob Steward Healthc Epidemiol. 2023;3(1):e168. doi:10.1017/ash.2023.447
19. Marra AR, Kobayashi T, Suzuki H, et al. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Healthc Epidemiol. 2022;2(1):e192. doi:10.1017/ash.2022.336
20. Ghazy RM, Ashmawy R, Hamdy NA, et al. Efficacy and Effectiveness of SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis. Vaccines (Basel). 2022;10(3):350. doi:10.3390/vaccines10030350
21. Chemaitelly H, Ayoub HH, Tang P, et al. Long-term COVID-19 booster effectiveness by infection history and clinical vulnerability and immune imprinting: a retrospective population-based cohort study. Lancet Infect Dis. 2023;23(7):816-27. doi:10.1016/S1473-3099(23)00058-0
22. Adly HM, Saleh SAK, Garout MA, et al. Post COVID-19 Symptoms Among Infected Vaccinated Individuals: A Cross-Sectional Study in Saudi Arabia. J Epidemiol Glob Health. 2023;13(4):740-50. doi:10.1007/s44197-023-00146-9
23. Catala M, Mercade-Besora N, Kolde R, et al. The effectiveness of COVID-19 vaccines to prevent long COVID symptoms: staggered cohort study of data from the UK, Spain, and Estonia. Lancet Respir Med. 2024;12(3):225-36. doi:10.1016/S2213-2600(23)00414-9
24. Byambasuren O, Stehlik P, Clark J, et al. Effect of covid-19 vaccination on long covid: systematic review. BMJ Med. 2023;2(1):e000385. doi:10.1136/bmjmed-2022-000385
25. Watanabe A, Iwagami M, Yasuhara J, et al. Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis. Vaccine. 2023;41(11):1783-90. doi:10.1016/j.vaccine.2023.02.008
26. Ceban F, Kulzhabayeva D, Rodrigues NB, et al. COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis. Brain Behav Immun. 2023;111:211-29. doi:10.1016/j.bbi.2023.03.022
27. Boretti A. mRNA vaccine boosters and impaired immune system response in immune compromised individuals: a narrative review. Clin Exp Med. 2024;24(1):23. doi:10.1007/s10238-023-01264-1
28. Di Domenico L, Goldberg Y, Colizza V. Planning and adjusting the COVID-19 booster vaccination campaign to reduce disease burden. Infect Dis Model. 2025;10(1):150-62. doi:10.1016/j.idm.2024.09.002
29. Patel V, Korsun M, Cervia J. Protective effects of booster dose of SARS-COV-2 vaccination against post-acute COVID-19 syndrome: A systematic review. J Investig Med. 2025:10815589251346963. doi:10.1177/10815589251346963
30. Bohm-Gonzalez ST, Detemple S, Gruss J, et al. Perspectives and involvement of children and adolescents during the decision-making process of their Covid-19 vaccination. Patient Educ Couns. 2025;130:108476. doi:10.1016/j.pec.2024.108476
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Copyright (c) 2026 Akzhan M. Madenbayeva, Yerlan Sh. Bazargaliyev , Saulesh S. Kurmangaliyeva , Khatimya Kh. Kudabayeva, Talgar S. Abilov

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