A prospective cohort study for characterization and predictive factors of long-term POST-COVID interstitial changes

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INTRODUCTION: Chronic interstitial lung changes are potential long-term sequelae of severe COVID-19. This study aims to evaluate the prevalence and type of interstitial changes over time and identify serum biomarkers associated with persistent lung abnormalities. METHODS: Prospective, multicenter, observational cohort study of patients with severe COVID-19 pneumonia between March 2020 and June 2021. Clinical evaluation, pulmonary function tests (PFTs), and chest high-resolution computed tomography (HRCT) were performed at baseline and up to 24 months. Serum biomarkers were assessed at baseline and at 12 months. RESULTS: Of the 290 patients enrolled, 247 completed the follow-up. Mild dyspnea (mMRC1) was the most common residual symptom. PFTs showed significant improvement: mean FVC increased from 88.8% to 99.5%, and DLCO from 71.6% to 82%. Among patients with baseline DLCO < 80% (n = 67), only 38.8% achieved normalization. Radiological improvement was observed in all patients, though 32% of the 118 patients assessed at 24 months still had residual changes, primarily mild reticulation, ground glass opacities, and lower lobes traction bronchiectasis. Pulmonary functional improvement correlated with radiological resolution, especially during the first year. Elevated baseline levels of MMP-7 and KL6 were associated with persistent interstitial abnormalities at 12 months. CONCLUSION: Severe COVID-19 survivors exhibit progressive functional and radiological improvement, particularly within the first year. However, a subset of patients shows long-term interstitial changes. Elevated MMP-7 and KL-6 levels may help identify individuals at higher risk for persistent interstitial changes.

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