Booster dose of COVID-19 vaccine and its effectiveness against post COVID-19 condition in individuals with pre-existing immunity: a sequential propensity score-matched cohort study.

Background: COVID-19 vaccination before primary infection is associated with decreased risk for post COVID-19 condition, but its effectiveness in populations with pre-existing immunity against SARS-CoV-2 is unknown. Our aim was to assess the COVID-19 vaccine effectiveness against post COVID-19 condition of four doses compared with three doses, both in the general population and in subpopulations with and without risk factors for severe acute COVID-19. Methods: In this, sequential, propensity score-matched cohort study conducted between 27 December 2020 and 29 February 2024, we included adults (≥18 years) who had received their third dose of COVID-19 vaccine, had no previous diagnosis of post COVID-19 condition, and who were successfully matched. At each index date (the date of the fourth dose for the exposed), an individual who had not yet received a fourth dose was included as unexposed, using exact matching followed by propensity score matching. Propensity scores were estimated based on socioeconomic factors, comorbidities, health-seeking behaviours, previous COVID-19, and prescribed medications. Individuals were followed from index date until diagnosis of post COVID-19 condition, moving out of study counties, death, new vaccination, six months after index date, or end of follow-up. The primary outcome was a clinical diagnosis of post COVID-19 condition from primary or specialist care. Findings: In total, 801,869 exposed individuals who received a fourth dose were successfully matched with 801,869 individuals with three doses. The incidence rate of post COVID-19 condition in the group with three doses was 1.67 per 1000 person-years (95% CI 1.52-1.83), compared with 1.14 per 1000 person-years (95% CI 1.02-1.28) in the four-dose group. In Cox regression analyses, a fourth vaccine dose was associated with a decreased risk of being diagnosed with post COVID-19 condition, with a vaccine effectiveness of 31% (95% CI 22-38). Among those with risk factors for severe acute COVID-19, the incidence rates of post COVID-19 condition were 2.14 per 1000 person-years (95% CI 1.91-2.39) for three doses and 1.32 per 1000 person-years (95% CI 1.07-1.54) for four doses, with a vaccine effectiveness of 38% (95% CI 29-47) for the fourth dose against post COVID-19 condition. Interpretation: Receiving a fourth dose of COVID-19 vaccine was associated with a lower risk of being diagnosed with post COVID-19 condition compared with three doses, although the absolute risk reduction was small. Due to the observational design of the study, residual confounding cannot be excluded. Funding: Swedish state under the agreement between the Swedish government and the county councils (the ALF-agreement), the Swedish Research Council, King Gustaf V's and Queen Victoria's Foundation, the SciLifeLab from the Knut and Alice Wallenberg Foundation, the Swedish Research Council for Health, Working Life, and Welfare (FORTE), the Swedish Society for Medical Research (SSMF), and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS).