Impact of COVID-19 vaccination on long COVID: a systematic review and meta-analysis
Background The impact of COVID-19 vaccination on preventing or treating long COVID is unclear. We aim to assess the impact of COVID vaccinations administered (i) before and (ii) after acute COVID-19, including vaccination after long COVID diagnosis, on the rates or symptoms of long COVID. Methods We searched PubMed, Embase, Cochrane COVID-19 trials, and Europe PMC for preprints from 1 Jan 2020 to 16 Feb 2022. We included trials, cohort, and case control studies reporting on long COVID cases and symptoms with vaccine administration both before and after COVID-19 diagnosis as well as after long COVID diagnosis. Risk of bias was assessed using ROBINS-I. Results We screened 356 articles and found no trials, but 6 observational studies from 3 countries (USA, UK, France) that reported on 442,601 patients. The most common long COVID symptoms studied include fatigue, cough, loss of smell, shortness of breath, loss of taste, headache, muscle ache, trouble sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. Four studies reported data on vaccination before SARS-CoV-2 infection, of which three showed statistically significant reduction in long COVID: the odds ratio of developing long COVID with one dose of vaccine ranged between OR 0.22 to 1.03; with two doses OR 0.51 to 1; and with any dose OR 0.85 to 1.01. Three studies reported on post-infection vaccination with odds ratios between 0.38 to 0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. Studies failed to adjust for potential confounders such as other protective behaviours, and missing data, thus increasing the risk of bias, and decreasing the certainty of evidence to low. Discussion Current studies suggest that COVID-19 vaccinations may have protective and therapeutic effects on long COVID. However, more robust comparative observational studies and trials are urgently needed to clearly determine effectiveness of vaccines in prevention and treatment of long COVID. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement OB is supported by NHMRC Grant APP1106452. PG is supported by NHMRC Australian Fellowship grant 1080042. There was no funding source for this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript
