Authors: Christine Azzopardi , Joelle Azzopardi , Peter Fsadni , Luca Conti

Abstract

Background
Familial pulmonary fibrosis (FPF) accounts for 10–20% of idiopathic pulmonary fibrosis cases and is associated with mutations in telomere-related genes, including TERT, TERC, RTEL1, PARN, and more recently CTC1. Telomere dysfunction predisposes to progressive fibrotic interstitial lung disease (ILD) and may increase susceptibility to environmental triggers. Emerging evidence suggests that COVID-19 pneumonitis can unmask or accelerate fibrosis in genetically predisposed individuals. We report a case of genetically confirmed FPF due to a likely pathogenic CTC1mutation presenting with progressive post-COVID pulmonary fibrosis.

Case Presentation
A 59-year-old woman with post-COVID pulmonary fibrosis presented with progressive dyspnoea, orthopnoea, and functional decline over six months. She required long-term oxygen therapy (5 L/min). Family history was significant for two first-degree relatives with usual interstitial pneumonia. Pulmonary function tests showed severe restriction (FVC 48%, DLCO 19%). Imaging evolved from organizing pneumonia during acute COVID-19 to established bilateral fibrotic ILD with traction bronchiectasis and features suggestive of pulmonary hypertension, confirmed on right heart catheterisation (mean PAP 38 mmHg). Autoimmune workup was largely negative aside from ANA positivity. Pirfenidone was discontinued due to hepatotoxicity. Genetic testing identified a heterozygous CTC1 variant (c.2518C>T; p.Arg840Trp), classified as likely pathogenic. She was commenced on nintedanib and referred for lung transplantation.

Conclusion
This case highlights the interplay between telomere-related genetic predisposition and viral injury in FPF. COVID-19 may accelerate fibrotic progression in susceptible individuals. Early genetic testing, multidisciplinary management, and timely transplant referral are crucial, with careful monitoring for treatment-related and post-transplant complications.

Keywords: Pulmonary fibrosis, COVID-19, telomere, CTC1 protein, case report.