SARS-CoV-2 reinfection in interstitial lung disease patients and its association with clinical deterioration: a two-year prospective cohort study.

BACKGROUND: The COVID-19 pandemic has raised concerns about respiratory sequelae, particularly in the patients with preexisting interstitial lung disease (ILD). This study aimed to evaluate the longitudinal impacts of SARS-CoV-2 reinfection on patients with preexisting ILD, focusing on differential outcomes between single and multiple infection episodes. METHODS: A prospective cohort study was conducted (December 2022-March 2023), enrolling 347 adults with preexisting ILD and confirmed COVID-19 infection. Follow-up assessments were performed at baseline, 6-, 12-, and 24-month intervals. Data included demographics, pulmonary function tests (PFTs), high-resolution computed tomography (HRCT) scores, and clinical outcomes. Composite deterioration endpoint incorporating acute exacerbation (AE), decline in forced vital capacity (FVC), decline in diffusing capacity (DLCO), and radiographic progression of lung fibrosis on HRCT. RESULTS: Among 347 patients (82.13% single infection, 17.87% multiple infections), the multiple infection group exhibited significantly higher disease deterioration rates (61.29% vs. 41.75%, P = 0.005). Multivariable Cox analysis identified multiple infections (HR = 1.50, 95% CI 1.03-2.19), higher baseline fibrosis scores (HR = 1.64), respiratory failure (HR = 1.84), and COVID-19 pneumonia (HR = 1.58) as independent risk factors. Patients with multiple infections showed accelerated FVC% decline (P = 0.016). All-cause mortality did not differ significantly between groups (11.29% vs. 9.12%, P = 0.598). Subgroup analyses suggested broadly consistent risks across ILD subtypes. CONCLUSION: Repeated SARS-CoV-2 infections may be associated with disease deterioration in patients with preexisting lung fibrosis. CLINICAL TRIAL NUMBER: Not applicable.