Overlapping Systemic Proteins in COVID-19 and Lung Fibrosis Associated with Tissue Remodeling and Inflammation

<b>Background/Objectives:</b> A novel patient group with chronic pulmonary fibrosis is emerging post COVID-19. To identify patients at risk of developing post-COVID-19 lung fibrosis, we here aimed to identify systemic proteins that overlap with fibrotic markers identified in patients with idiopathic pulmonary fibrosis (IPF) and may predict COVID-19-induced lung fibrosis. <b>Methods:</b> Ninety-two proteins were measured in plasma samples from hospitalized patients with moderate and severe COVID-19 in Sweden, before the introduction of the vaccination program, as well as from healthy individuals. These measurements were conducted using proximity extension assay (PEA) technology with a panel including inflammatory and remodeling proteins. Histopathological alterations were evaluated in explanted lung tissue. <b>Results:</b> Connecting to IPF pathology, several proteins including decorin (DCN), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) and chemokine (C-X-C motif) ligand 13 (CXCL13) were elevated in COVID-19 patients compared to healthy subjects. Moreover, we found incrementing expression of monocyte chemotactic protein-3 (MCP-3) and hepatocyte growth factor (HGF) when comparing moderate to severe COVID-19. <b>Conclusions:</b> Both extracellular matrix- and inflammation-associated proteins were identified as overlapping with pulmonary fibrosis, where we found DCN, TNFRSF12A, CXCL13, CXCL9, MCP-3 and HGF to be of particular interest to follow up on for the prediction of disease severity.