Bronchial Hyperreactivity in the COVID-19 Era: The Impact of SARS-CoV-2 Infection and COVID-19 Vaccination in Patients with Respiratory Symptoms

Introduction: Persistent respiratory symptoms are commonly reported following coronavirus disease 2019 (COVID-19). Although COVID-19 vaccines are effective, concerns remain regarding their potential impact on airway hypersensitivity. The relationship between SARS-CoV-2 infection, vaccination, and bronchial hyperresponsiveness remains unclear. Materials and Methods: This retrospective study included adults aged ≥ 18 years who underwent methacholine provocation testing. Participants were categorized into four groups according to their history of SARS-CoV-2 infection and COVID-19 vaccination: no infection/no vaccination (NI-NV), vaccination/no infection (V-NI), no vaccination/infection (NV–I), and vaccination/infection (V–I). Airway hypersensitivity was defined as a ≥ 20% reduction in forced expiratory volume in one second (FEV1) following methacholine challenge. Multivariable logistic regression analysis was performed to evaluate independent associations. Results: A total of 340 participants were included (NI-NV: n=36; V-NI: n=163; NV-I: n=25; V-I: n=116). No significant differences were observed in methacholine positivity, pulmonary function parameters, or PC20 values across groups (all p> 0.05). In multivariable analysis, neither prior infection (adjusted OR 0.99, 95% CI 0.63– 1.55) nor vaccination (adjusted OR 1.06, 95% CI 0.60– 1.88) was independently associated with bronchial hyperresponsiveness. Smoking was significantly associated with methacholine positivity (adjusted OR 3.33, 95% CI 1.43– 7.77). Symptom severity differed among groups, with higher cough and sputum scores in the NI-NV group and greater dyspnea severity in the NV-I group. Conclusion: Neither prior SARS-CoV-2 infection nor COVID-19 vaccination was associated with increased airway hypersensitivity after adjustment for confounders. Despite similar objective airway responsiveness, symptom severity varied across groups, suggesting a dissociation between subjective respiratory symptoms and measurable bronchial hyperresponsiveness. Keywords: COVID-19 infection, vaccination, provocation test, airway hypersensitivity