While effectiveness of the vaccination against severe manifestations of acute COVID-19 has repeatedly been shown (see Infobox), evidence of protection against Long COVID has not been as strong. On November 22, 2023, a group from Sweden published the largest population-based study to date, assessing the effectiveness of COVID-19 vaccination to protect against Long COVID. The researchers used real-world data from Sweden's national registers as part of a nationwide observational study of the COVID-19 pandemic in Sweden called SCIFI-PEARL project.
Study Design
The study analyzed data from adults (≥18 years) residing in Region Stockholm and Region Västra Götaland, which cover approximately 40% of the Swedish population. Vaccination status was determined by data from the Swedish National Vaccination Register.
Individuals with a COVID-19 diagnosis registered between December 2020, and February 2022, were included. The study period was chosen to coincide with simultaneous vaccination and PCR testing in Sweden. Participants were followed from 28 days after COVID-19 index date (date the individual was registered as having COVID-19) until Long COVID diagnosis, vaccination, reinfection, death, emigration, or the end of follow-up end of November 2022. Participants who were vaccinated, emigrated, or died within the 28 days after infection, were excluded.
Protective effect of vaccination against Long COVID
During the study period, 649,071 individuals in Sweden were registered with COVID-19 for the first time. After exclusions, 589,722 individuals met the study’s criteria. Among the study population, 50.8% had received at least one COVID-19 vaccine dose before the index date. Vaccinated individuals were more likely to be women, older, and infected during the omicron era. Median follow-up was 129 days, and the most common reason for ending follow-up was vaccination. Unvaccinated individuals had a more than threefold higher proportion of Long COVID diagnoses compared to those vaccinated before infection (1.4% vs. 0.4%).
Non-vaccinated individuals have 3.4 times higher Long COVID risk.
Subgroup analyses indicated slightly lower vaccine effectiveness the longer ago a participant received their last dose. However, at 600 days post-vaccination, Long COVID incidence remained much lower in vaccinated, versus non-vaccinated individuals.
Receiving at least one vaccine dose before the COVID-19 index date was associated with a reduced risk for Long COVID.
The authors noted vaccine effectiveness of 21% for one dose, 59% for two doses and 73% for three or more doses, meaning vaccinated participants were up to 73% less likely to develop Long COVID. The vaccine effectiveness against Long COVID was significant no matter how severe the initial infection.
When comparing individuals who received at least one dose, men showed higher vaccine effectiveness than women (64% vs 54%). The effectiveness varied by age group, with the highest in individuals aged 55-64 years (69%) and lowest in 18–34-year-olds (28%). We at Altea suppose that this lower effectiveness in younger individuals could be related to the fact that young, healthy individuals were among the last to be vaccinated and would thus have received less doses than the other age groups. As the authors do not comment on the low number in the youngest group, a follow-up publication where subgroups are divided into number of doses received would be of high interest.
Lastly, the data showed that reinfections with COVID-19 during the study period were three times lower in the vaccinated group (1.1%) versus the unvaccinated group (3.3%).
Conclusion
The study concludes that receiving COVID-19 vaccine doses within the primary vaccination series before infection is strongly associated with a reduced risk of Long COVID. This protective effect was also shown for reinfection. The findings emphasize the importance of achieving complete primary vaccination coverage not only to mitigate severe acute COVID-19 but also to alleviate the burden of Long COVID in the population.
Other studies indicate that a benefit could occur in individuals already affected by Long COVID where vaccination might have a protective as well as therapeutic effect. However, more robust scientific data is needed. As mentioned previously in an interview with Prof. Puhan, vaccination should be discussed individually with a health care professional considering if the health status permits it or not.
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