Prognostic Value of Cellular Senescence, Lymphatic Proliferation, and Histological Findings in the Follow-up of Post-covid-19 Interstitial Lung Disease Sequelae.

BACKGROUND In some patients post COVID-19 interstitial lung disease (ILD) sequelae persist beyond 6 months after hospital discharge. Little is known about the pathophysiology of this condition. This study aimed to determine the prognostic value of certain histopathological findings, cellular senescence, and lymphatic proliferation in patients with ILD sequelae. METHODS This prospective observational study of patients hospitalized at Vall d’Hebron University Hospital due to COVID-19 pneumonia and presenting respiratory symptoms, radiological alterations, and pulmonary function test impairment during the 3-month follow-up visit after discharge. Lung cryobiopsies were performed, and the histopathological findings and expression of senescence and lymphatic proliferation (P16 and D2-40) were analyzed. RESULTS Between March 2020 and February 2021, 4,332 patients were hospitalized at Vall d’Hebron University Hospital due to COVID-19 pneumonia, and 1,403 were visited in the Respiratory Clinic 3 months after discharge. The first 66 patients presenting with respiratory symptoms, radiological alterations, and decreased pulmonary function tests during the post hospitalization follow-up underwent cryobiopsy for diagnostic purposes. Multivariate regression showed that Masson bodies in the 3-month cryobiopsy were related to a higher forced vital capacity at 6 months whereas higher expression of senescence and lymphatic proliferation markers, such as P-16 and D2-40, in the histological samples were related to decreased carbon monoxide transfer test values at 6 months. CONCLUSION Senescence and lymphatic proliferation are related to worse pulmonary function outcomes in the mid-term follow-up of patients with post-COVID-19 ILD.