Impact of COVID-19 vaccination on long COVID: a systematic review and meta-analysis

BackgroundThe 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. MethodsWe 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. ResultsWe 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. DiscussionCurrent 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.