Cellular senescence and lymphatic proliferation in lung tissue are associated with impaired gas exchange in mid-term follow-up, suggesting their potential as prognostic markers in post-COVID-19 ILD.
Key Findings
Results
Masson bodies identified in 3-month cryobiopsy were associated with higher forced vital capacity at 6 months follow-up.
Finding derived from multivariate regression analysis of cryobiopsy histopathological findings
Masson bodies are histological features associated with organizing pneumonia patterns
The relationship suggests that certain histological patterns at 3 months may predict better pulmonary function outcomes at 6 months
Study performed at Vall d'Hebron University Hospital between March 2020 and February 2021
Results
Higher expression of the senescence marker P-16 in lung tissue was associated with decreased carbon monoxide transfer test (DLCO) values at 6 months.
P-16 is a marker of cellular senescence analyzed in lung cryobiopsy samples
Association identified through multivariate regression analysis
DLCO impairment reflects reduced gas exchange capacity
Samples were obtained from the first 66 patients presenting with respiratory symptoms, radiological alterations, and decreased pulmonary function tests at 3-month post-hospitalization follow-up
Results
Higher expression of the lymphatic proliferation marker D2-40 in lung tissue was associated with decreased carbon monoxide transfer test values at 6 months.
D2-40 is a marker of lymphatic proliferation analyzed immunohistochemically in cryobiopsy samples
Association identified through multivariate regression analysis alongside P-16
Finding suggests lymphatic proliferation contributes to impaired gas exchange in post-COVID-19 ILD
Cryobiopsies were performed at the 3-month follow-up visit after hospital discharge
Methods
A large proportion of hospitalized COVID-19 patients developed persistent respiratory sequelae requiring follow-up and biopsy evaluation.
4332 patients were hospitalized at Vall d'Hebron University Hospital due to COVID-19 pneumonia between March 2020 and February 2021
1403 patients were seen in the Respiratory Clinic 3 months after discharge
The first 66 patients presenting with respiratory symptoms, radiological alterations, and decreased pulmonary function tests underwent cryobiopsy for diagnostic purposes
This represents a prospective observational study design
Background
Post-COVID-19 ILD sequelae can persist beyond 6 months after hospital discharge in a subset of patients, and the pathophysiological mechanisms remain poorly understood.
The study was specifically designed to evaluate patients with ILD persisting beyond 6 months
Histopathological patterns, cellular senescence, and lymphatic proliferation were evaluated as potential prognostic factors
Lung cryobiopsies were used to analyze histopathological findings and expression of P16 and D2-40
The study identifies cellular senescence and lymphatic proliferation as novel pathophysiological mechanisms potentially involved in post-COVID-19 ILD
Florencia Pilia M, Sansano I, Varona D, Sánchez M, Espejo D, Culebras M, et al.. (2026). Prognostic value of senescence, lymphatic proliferation, and histology in post-COVID-19 interstitial lung disease.. Medicina clinica. https://doi.org/10.1016/j.medcli.2025.107252