A RECENT study has uncovered a new connection between genetic risk factors for idiopathic pulmonary fibrosis (IPF) and the development of post-COVID-19 lung abnormalities, suggesting a possible protective role of the MUC5B genetic variant.
Researchers examined 71 adults hospitalised for COVID-19 between March and May 2020, with an average age of 63 years (62% were male, 31% had a history of smoking, and 23% required mechanical ventilation). At 3 months post-discharge, high-resolution CT scans and pulmonary function tests were conducted to assess lung abnormalities, such as ground glass opacities and reticulation. Three genetic polymorphisms associated with IPF (MUC5B, ATP11A, and DPP9) were also analysed.
The MUC5B risk allele, a known factor in IPF susceptibility, demonstrated a surprising association with reduced ground glass opacities (β=−0.8, 95% CI: −1.5 to −0.1, P=0.02) and a trend towards improved lung function, as indicated by higher diffusion capacity for carbon monoxide (β=8.8, 95% CI: −1.2 to 18.8, P=0.08). This suggests that the MUC5B variant may protect against post-COVID-19 lung abnormalities. Notably, no significant link was found between any genetic variants and reticulation, a marker of lung scarring.
These findings build on previous research that identified MUC5B as protective against severe COVID-19-related hospitalisation. While the gene variant increases susceptibility to IPF, it may also enhance mucin production, aiding immune defence and reducing postinfectious lung damage. However, this protective effect could come at a long-term cost, as the same mechanism may drive recurrent, aberrant alveolar repair, a hallmark of IPF.
This study is the first to explore the relationship between IPF genetic risk factors and radiologic outcomes after severe COVID-19, raising new questions about the genetic interplay between immune defence and long-term lung health. Further research could inform strategies to mitigate long-term respiratory complications post-COVID-19.
Ada Enesco, EMJ
Reference
Marinescu DC et al. Role of IPF genetic risk loci in post-COVID-19 lung abnormalities: a cohort study. BMJ Open Respir Res. 2025;12(1):e002725.
