The alveolar fibroproliferative response in moderate to severe COVID-19-related acute respiratory distress syndrome and one-year follow up

Background: COVID-19-related acute respiratory distress syndrome (ARDS) can lead to long-term pulmonary fibrotic lesions. Alveolar fibroproliferative response (FPR) is a key factor in the development of pulmonary fibrosis. N-terminal-peptide of procollagen III (NT-PCP-III) is a validated biomarker for activated FPR in ARDS. This study aimed to assess the association between dynamic changes in alveolar FPR and long-term outcomes, as well as mortality in COVID-19-ARDS patients. Methods: We conducted a prospective cohort study of 154 COVID-19-ARDS patients. We collected bronchoalveolar lavage (BAL) and blood samples for measurement of 17 pulmonary fibrosis biomarkers, including NT-PCP-III. We assessed pulmonary function and chest computed tomography (CT) at 3 and 12 months after hospital discharge. We performed joint modelling to assess the association between longitudinal changes in biomarker levels and mortality at day 90 after starting mechanical ventilation. Results: 154 patients with 284 BAL samples were analysed. Of all patients, 40% survived to day 90, of whom 54 completed the follow-up procedure. A longitudinal increase in NT-PCP-III was associated with increased mortality (HR 2.89, 95% CI: 2.55-3.28; p<0.001). Forced vital capacity and diffusion for carbon monoxide were impaired at 3 months but improved significantly at one year after hospital discharge (p=0.03 and p=0.004, respectively). There was no strong evidence linking alveolar FPR during hospitalization and signs of pulmonary fibrosis in pulmonary function or chest CT images during one-year follow-up. Conclusion: In COVID-19-ARDS patients, alveolar FPR during hospitalization was associated with higher mortality but not with the presence of long-term fibrotic lung sequelae within survivors.