COVID-19 infection raises respiratory type-2 inflammatory disease risk, whereas vaccination is protective

Olbrich H, Preuß SL, Kridin K, Hernandez G, Thaçi D, Ludwig RJ, Curman P.  J Allergy Clin Immunol. 2025 Aug 12:S0091-6749(25)00858-9. doi: 10.1016/j.jaci.2025.07.030. 

ABSTRACT

Background

COVID-19 infection and vaccination have unclear impacts on type-2 inflammatory diseases. Although viral infections can drive immune dysregulation, the extent to which COVID-19 infection and vaccination affect type-2 inflammatory diseases in various organ systems remains underexplored.

Objective

We aimed to assess the risk of new-onset type-2 inflammatory diseases after COVID-19 infection and vaccination.

Methods

 Flow-chart depicting the study outline.

We conducted a large-scale retrospective matched cohort study within a United States electronic health records database of over 118 million patients. Three cohorts were defined: individuals with COVID-19 infection (973,794), individuals with COVID-19 vaccination (691,270), and unexposed controls (4,388,409). Propensity-score matching balanced demographic and clinical covariates. We calculated hazard ratios for incident asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis, and eosinophilic esophagitis over a three-month follow-up.

Results

COVID-19 infection significantly increased the risks of asthma (hazard ratio 1.656, 95% confidence interval 1.590–1.725), allergic rhinitis (1.272, 1.214–1.333), and chronic rhinosinusitis (1.744, 1.671–1.821). Risks for atopic dermatitis or eosinophilic esophagitis remained unchanged. In contrast, vaccination lowered the risks of asthma (0.678, 0.636–0.722) and chronic rhinosinusitis (0.799, 0.752–0.850). Direct comparison showed a two- to threefold greater risk of respiratory type-2 inflammatory diseases with infection than with vaccination.

Conclusion

COVID-19 infection is associated with a heightened risk of respiratory type-2 inflammatory diseases, whereas vaccination appears protective.

Clinical Implication

COVID-19 vaccination may reduce respiratory complications driven by type-2 inflammation, thereby diminishing disease burden.

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