Introduction: Long-term effects after SARS CoV-2 infection are increasingly described and include diffuse capacity (DLCO) impairment as well as residual radiological abnormalities (Guler SA, et al. Eur Respir J. 2021). Fibrotic pulmonary sequelae have been previously observed after other SARS infection (Ketai L, et al. J Thorac Imaging. 2006).

Aims: To identify biomarkers associated with lung fibrosis after COVID-19 in patients with lung functional impairment.

Method: 124 participants were recruited at the Inselspital, Bern University Hospital. Our cohort was divided into two groups according to lung functional impairment: 1) predicted DLCO <80% or 2) >80% at 4 months after the infection. Serum samples were analysed using a commercially available proteomic inflammation panel (Olink® Proteomics, Uppsala, Sweden). Welch Two Sample t-test were performed with Olink® Insights Stat Analysis (p-value < 0.05).

Results: 22 proteins showed significant differences comparing both groups. DLCO-impaired compared with non-impaired patients showed significant higher serum levels of the following lung fibrosis markers: IL15-RA, CXCL9, EN-RAGE, CSF-1, OPG, MMP10, 4E-BP1, and CCL11 (p<0.05), which correlated with DLCO. In addition, impaired patients showed persistent inflammation (e.g. IL6, IL-8, MCP-1, MCP-3, CCL3 p=0.01). Moreover, increased levels of biomarkers associated with worse acute COVID-19 outcome were found in these patients (e.g. IL-10RB, TNFRSF9, HGF, CDCP1 and PDL-1 (p<0.05)).

Conclusion: Pro-fibrotic markers are enhanced in COVID-19 patients with persistent DLCO impairment 4 months after acute infection.Persistent inflammation after viral infection might contribute to lung functional impairment.