ABSTRACT
ImportanceCharacterizing the effect of vaccination on long COVID allows for better healthcare recommendations. ObjectiveTo determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection. Design, Settings, and ParticipantsRetrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C). ExposuresPre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination. Main Outcomes and MeasuresTwo approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards. ResultsIn both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75). Conclusions and RelevanceLong COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections. Key PointsO_ST_ABSQuestionC_ST_ABSDoes vaccination prior to COVID-19 onset change the risk of long COVID diagnosis? FindingsFour observational analyses of EHRs showed a statistically significant reduction in long COVID risk associated with pre-COVID vaccination (first cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; second cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75). MeaningVaccination prior to COVID onset has a protective association with long COVID even in the case of breakthrough infections.