(SLC-056) COVID-19 vaccine effectiveness against Post COVID-19 condition among 1,292,557 individuals with pre-existing immunity against SARS-CoV-2: a population-based cohort study.

Background: Although the World Health Organization no longer considers COVID-19 a public health emergency of international concern, SARS-CoV-2 continues to circulate in the population, causing infections. We have previously shown that vaccination before primary infection is associated with a decreased risk for post COVID-19 condition (PCC), but it is still unknown whether this effect is present in a population with pre-existing immunity against SARS-CoV-2.

Objectives: To investigate the COVID-19 vaccine effectiveness against PCC in a population with pre-existing immunity against SARS-CoV-2.

Methods: In this register-based cohort study, we included all adult (≥18 years) residents in the two largest regions in Sweden who; 1) had received their third dose of COVID-19 vaccine between 2 Nov 2021 and 25 May 2022, 2) were not diagnosed with PCC before index date, and 3) were successfully matched. At index date of an exposed individual (who received dose four), an individual who had not yet received a fourth dose was matched as unexposed. Exact matching was based on year of birth, sex, region of residence, and week of the third vaccine dose. Propensity scores (PS) for a time-dependent exposure were estimated for each individual. PS-matching was performed within each stratum considering socioeconomic factors, comorbidities, health seeking behaviour, and prescribed medications. The primary outcome was a clinical diagnosis of PCC (ICD-10 diagnosis code U09.9) in primary or specialist care. Individuals were followed from index date until PCC diagnosis, emigration, move out of study regions, death, new vaccination, or end of follow-up (29 Feb 2024), whichever came first. The vaccine effectiveness (1 - hazard ratio [HR] x 100) against PCC was estimated using Cox regression models with doubly robust adjustments.

Results: After 12 months, 0.10% (95% confidence interval [95% CI] 0.09-0.11) of the individuals with three doses were diagnosed with PCC, compared to 0.08% (95% CI 0.07-0.09) among those who received a fourth vaccine dose, resulting in an absolute unadjusted difference in cumulative incidence of 0.02% (95% CI 0.007-0.03). In Cox regression analyses with doubly robust adjustment, receiving a fourth vaccine dose was associated with a decreased risk of being diagnosed with PCC (HR 0.72, 95% CI 0.62-0.83), with a vaccine effectiveness of 28%.

Conclusions: In a population with pre-existing immunity against SARS-CoV-2, our results indicate that there is an added continued benefit of receiving a fourth dose of COVID-19 vaccine, compared to remaining with three doses, with regard to the risk of being diagnosed with PCC. However, given the absolute risk reduction of 0.02%, the overall clinical impact of this added benefit may be limited.