The risk of new-onset respiratory type 2 inflammatory diseases is higher after a COVID-19 infection.A study shows an association between COVID-19 infection and an elevated risk of new-onset respiratory type 2 inflammatory diseases (T2IDs), while vaccination remains protective against such diseases.
“Our large-scale matched cohort study demonstrates an elevated risk of respiratory T2IDs, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis (CRS), in adults following a COVID-19 infection [in the primary analysis],” the investigators said.
At 3 months, compared with unexposed controls, COVID-19 infection was associated with a significantly increased risk of asthma (HR, 1.656), allergic rhinitis (HR, 1.272), and CRS (HR, 1.744; p<0.0001 for all). [J Allergy Clin Immunol 2026;157:517-524]
The results were consistent across all five sensitivity analyses (SAs), with more pronounced risk differences in SA3 (extended propensity-score matching), particularly for asthma and CRS (HRs, 1.951 and 2.031; p<0.0001 for both).
The risks for these T2IDs were also elevated in the comparison between COVID-19 infection and vaccination (HRs, 2.463, 1.402, and 2.227 for asthma, allergic rhinitis, and CRS, respectively; p<0.0001 for all). The results were also consistent across all SAs.
“The consistent risk elevation … suggests that T2I may be a key mechanism driving respiratory sequelae after COVID-19 infection,” the researchers said.
The risks were notably mitigated by COVID-19 vaccination (asthma: HR, 0.678; p<0.0001, allergic rhinitis: HR, 0.927; p=0.044, and CRS: HR, 0.799; p<0.0001). Again, the findings were consistent across all SAs except for SA3, where significance was lost for all except asthma (HR, 0.775; p<0.0001).
The researchers noted that the elevated T2ID risk reversal following COVID-19 vaccination supports the theory linking T2 responses to viral immune response mechanisms. “As COVID-19 vaccinations attenuate infection incidence and severity, putative immune side effects of viral infection might be diminished, and such a positive vaccination effect aligns with the risk reversals observed.”
Of note, the risks for other T2IDs, such as atopic dermatitis (AD) and eosinophilic esophagitis (EoE), remained unaffected by COVID-19 infection (HR, 1.075; p=0.526 and HR, 0.961; p=0.998, respectively) or vaccination (HR, 1.074; p=0.767 and HR, 0.797; p=0.355).
Vaccination also increased the risk of AD in SA3 (HR, 1.483; p<0.0001), which aligns with results from a study on vaccination-related skin conditions. [J Clin Med 2024;13:4617] “[This result warrants] further investigation to elucidate potential links between vaccination and dermatologic outcomes,” the researchers said.
T2IDs represent a distinct group of immune-mediated chronic conditions affecting the skin, airways, and other organs. The core disease manifestations include AD, allergic asthma, CRS with nasal polyps, and EoE. [Front Immunol 2024;15:1285598]
Evidence on the association between COVID-19 and incident T2IDs in the general population remains scarce, as does data on the potential impact of COVID-19 vaccination.
Using a US electronic health records database comprising over 118 million patients, the researchers created three cohorts: individuals with COVID-19 infection (n=973,794), vaccination (n=691,270), and no documented infection or vaccination (n=4,388,409).
In the primary analysis, outcomes were assessed between day 1 and month 3 after the index event. The investigators chose a short time window to accurately capture acute immune responses, reduce confounder effects, and evaluate immediate risks of exposures. Five SAs were conducted to ensure the robustness of results.
“Interestingly, in our analysis, T2I responses following COVID-19 infection appeared to be restricted to the respiratory tract, as AD and EoE showed no increased risk. This could reflect higher viral loads in respiratory tissues compared with other organs, despite evidence of SARS-CoV-2 replication in non-respiratory organs such as the skin and gastrointestinal tract,” the investigators explained.
“The findings emphasize T2I as a possible driver of respiratory sequelae, showing that this response is primarily restricted to the respiratory tract,” they said.
The study also underscores the critical role of vaccination in reducing the burden of T2IDs, the researchers added. “This reinforces the importance of vaccination campaigns and public health messaging to address both direct and indirect consequences of COVID-19.”