COVID-19 severity and risk of SARS-CoV-2-associated asthma exacerbation by time since booster vaccination: a longitudinal analysis of data from the COVIDENCE UK study

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Abstract
Background: In several countries, COVID-19 booster vaccinations are offered annually to priority groups, but many people have not been vaccinated in over a year. We aimed to assess the association between time since booster vaccination and characteristics of breakthrough infection. We also assessed whether incident COVID-19 continued to associate with asthma exacerbations in boosted individuals, and whether risk of COVID-19-associated exacerbation was affected by time since vaccination. Methods: COVIDENCE UK is a prospective, longitudinal, population-based study of COVID-19. We included adult participants who had received ≥1 booster vaccination. Time since vaccination was binarised at 6 months or 12 months according to vaccine eligibility subgroup. We used logistic, Cox, and linear regression to obtain adjusted estimates for the association between time since vaccination and breakthrough infection severity, symptom duration, and acute changes to health-related quality of life (measured by the EQ-5D-3L Index). We then assessed the association of incident COVID-19 with asthma exacerbations using multilevel mixed models, by time since vaccination. Results: 7391 boosted participants reported a breakthrough infection. Across all eligibility subgroups, greater time since vaccination associated with increased odds of infection requiring bedrest ( vs milder symptoms), with the highest odds for adults aged 65–75 years (1.83 [95% CI 1.51–2.23] when vaccinated >6 months vs ≤6 months prior). However, we observed little evidence of association between time since vaccination and symptom duration. Vaccination >12 months prior ( vs ≤12 months) was associated with a small decrease in EQ-5D-3L Index among participants younger than 65 years (-0.03 points [-0.04 to -0.01]). Among 2100 participants with asthma, incident COVID-19 associated with increased risk of asthma exacerbation, both ≤12 months after vaccination (OR 5.31 [4.36–6.48]) and later (6.06 [3.23–11.38]), with a greater difference in point estimates when specifically considering severe asthma exacerbations (6.82 [4.88–9.54] for ≤12 months vs 10.06 [3.90–25.92] for >12 months). Conclusion: Longer time since booster vaccination consistently associates with more severe breakthrough infections, and may potentially increase risk of severe asthma exacerbations. These findings highlight the importance of ensuring those currently eligible receive their booster vaccinations, and the need for research on further vaccinations in people with asthma no longer eligible for boosters.
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