In a large register-based cohort study involving 589,722 residents from the two largest regions of Sweden, we uncovered a significant correlation between vaccination prior to first registered covid-19 and a decreased risk of receiving a diagnosis of PCC. In our study population, unvaccinated individuals showed an almost fourfold higher proportion of PCC diagnoses compared with those who were vaccinated before infection (1.4% vs. 0.4%). Additionally, we found a vaccine effectiveness against PCC of 58% for any dose within the primary vaccination series given before a first registered infection. This effectiveness increased with each dose in the series: 21% for one dose, 59% for two doses, and 73% for three or more doses.
Contextual Findings:
Earlier studies on vaccine effectiveness against the long-term effects of covid-19 have presented varying results, with some demonstrating protective effects but others failing to show an overall protective effect. However, these studies have been limited by heterogeneous methodologies, small study populations, and the inclusion of both vaccinated and unvaccinated individuals in the unvaccinated group. In contrast, our study utilized population-based survival data of 589,722 individuals and reported vaccine effectiveness separately for varying doses before covid-19.
With the inclusion of only clinical diagnoses of PCC as the outcome, our study aimed to provide a more comprehensive understanding of the relationship between vaccination and PCC. Additionally, we considered the median follow-up period of 129 days after a first registered infection, providing a more robust assessment of long-term effects.
Gender and Variant Considerations:
Our study also revealed that men showed a higher vaccine effectiveness against PCC than women. Additionally, we explored the potential effects of different variants, suggesting that individuals infected with the omicron variant exhibited a lower risk of developing long-term effects of covid-19. Moreover, in sensitivity analyses, our estimated vaccine effect remained consistent even with restrictions on the time between vaccination and acute infection.
Pathogenesis and Protective Mechanisms:
While the pathogenesis of PCC remains unclear, potential mechanisms include organ damage, abnormal immune activation during acute infection, and viral persistence. Our study indicated that covid-19 vaccines may protect against hospital admission, thus contributing to their protective effect against PCC. Furthermore, our analysis suggests that there may be pathways beyond the protective effect against hospital admission that contribute to the protective effect of covid-19 vaccines against PCC.
Strengths and Limitations:
The strengths of our study lie in its use of high-quality register-based data and its population-based design covering the two largest regions of Sweden. Additionally, we had access to individual-level data from primary healthcare as well as inpatient and outpatient specialist healthcare, allowing for a comprehensive understanding of the diagnosis of PCC. However, limitations include the potential misclassification of infection variants due to a lack of virus sequencing data and the exclusion of individuals with infections during the omicron period.
Overall, our study provides valuable insights into the relationship between covid-19 vaccination and the risk of PCC, shedding light on potential mechanisms and protective pathways.
