Clinical and Radiological Profile of Post-COVID Pulmonary Fibrosis: A Prospective Observational Study from India

Abstract

Background: Post-COVID pulmonary fibrosis (post-COVID PF) has emerged as a clinically significant sequela of SARS-CoV-2 infection, particularly following severe acute illness, with incompletely characterised clinical determinants, radiological patterns, functional impairment profiles, and fibrotic biomarker associations in Indian populations. This prospective observational study was designed to delineate the clinical and radiological profile of post-COVID PF in a tertiary care Indian cohort. Methods: A prospective observational study was conducted at Vardhman Mahavir Medical College, Safdarjung Hospital, New Delhi, India, enrolling 180 patients with confirmed prior SARS-CoV-2 infection assessed at the post-COVID follow-up clinic at 12 weeks following acute illness. Participants were categorised as post-COVID PF (n=120) or post-COVID without PF (n=60) based on HRCT chest findings. All patients underwent clinical assessment, spirometry with DLCO, six-minute walk test (6MWT), and measurement of inflammatory and fibrotic biomarkers including hs-CRP, serum ferritin, LDH, IL-6, TGF-β1, and KL-6. HRCT patterns were classified as UIP-like, NSIP-like, or organising pneumonia-like. Multivariable logistic regression was used to identify independent predictors of post-COVID PF. Follow-up was conducted at 6 months. Results: The post-COVID PF cohort was significantly older (54.8 ± 11.3 vs 48.2 ± 10.6 years; p=0.001), had a higher prevalence of severe acute COVID-19 (80.0% vs 40.0%; p<0.001), ICU admission (51.7% vs 18.3%; p<0.001), and mechanical ventilation (28.3% vs 6.7%; p<0.001). Restrictive spirometry was present in 81.7% of the PF group, with markedly reduced DLCO (48.6 ± 14.2% predicted). HRCT predominantly demonstrated an NSIP-like pattern (43.3%), followed by UIP-like (38.3%) and organising pneumonia-like (18.3%) patterns, with ground-glass opacity, reticulation, and traction bronchiectasis as the most frequent findings. KL-6, TGF-β1, serum ferritin, and IL-6 were significantly elevated in the PF group (all p<0.001). On multivariable logistic regression, severe acute COVID-19 (OR 5.1), KL-6 ≥500 U/mL (OR 4.4), TGF-β1 ≥30 pg/mL (OR 3.6), ICU admission (OR 3.2), serum ferritin ≥400 ng/mL (OR 3.1), and mechanical ventilation (OR 3.8) were independent predictors of post-COVID PF (all p<0.05). Conclusion: PostCOVID pulmonary fibrosis in Indian patients is characterised by predominantly NSIP-like and UIP-like HRCT patterns, severe restrictive physiology with profoundly impaired DLCO, and a distinct fibrotic biomarker signature. Severity of acute COVID-19, ICU admission, and elevated KL-6 and TGF-β1 are the strongest independent predictors. These findings support systematic post-COVID pulmonary follow-up with HRCT and PFTs, early antifibrotic consideration in eligible patients, and biomarker-guided risk stratification in Indian postCOVID clinical practice.