Effectiveness of COVID-19 vaccines against post-COVID-19 condition/long COVID: systematic review and meta-analysis

Background: Persons infected with SARS-CoV-2 can develop long-term symptoms known as postCOVID-19 condition (PCC; symptoms >=3 months after infection) or long COVID (LC; symptoms >=1 month after infection). Vaccination against COVID-19 might prevent PCC/LC, but the extent of protection is unclear. Objective(s): The aim of this systematic review was to evaluate the vaccine efficacy/effectiveness (VE) of COVID-19 vaccines given prior to SARS-CoV-2 infection in preventing PCC or LC. Methods Data sources: Studies were identified in Embase, MEDLINE, PreView, COVID-19 L.OVE repository, and Cochrane Library up to August 1, 2024. Study eligibility criteria, Participants, and Interventions: Randomized controlled trials and nonrandomized studies of interventions (NRSI) that investigated immunization with a COVID-19 vaccine before SARS-CoV-2 infection were eligible, irrespective of participant age and sex. Assessment of risk of bias: Risk of bias was assessed using the ''Risk Of Bias In Nonrandomized Studies-of Interventions'' tool. Methods of data synthesis: Primary outcome was PCC, secondary outcomes were LC, time until reconvalescence, limitations in everyday activity, and quality of life. Meta-analyses were primarily conducted using the random-effects model. Result(s): A total of 6423 records were screened, and 65 NRSI reporting adjusted estimates were included, comprising >5.7 mio. participants. VE for >=1 vaccine dose against PCC was 41.0% (95% CI 27.8%; 51.7%; 22 NRSI, certainty of evidence: low). VE after 1, 2, or 3 doses versus unvaccinated was 19.1% (-119.4%; 70.2%, 3 NRSI), 43.2% (4.5%; 66.2%; 4 NRSI), and 70.0% (30.0%; 87.0%; 1 NRSI), respectively. In <18 years old, VE against PCC was 26% for >=1 dose (-4%; 48%, 1 NRSI) and in >60 years old 41% (17%; 59%, 1 NRSI). VE after pre-Omicron-SARS-CoV-2 infection was 32.1% (-54.3%; 70.1%, 3 NRSI) and 20.9% (-10.1%; 43.3%, 2 NRSI) after Omicron infection. Sensitivity analyses indicated no influence of risk of bias and effect measure. Conclusion(s): COVID-19 vaccines may be moderately effective in preventing PCC/LC. VE may increase with the number of vaccine doses administered. Copyright © 2025 The Authors