Biomarkers in ICU-treated Covid-19 patients 4 and 10 months after discharge: evidence for persistent inflammation and remodeling

<bold>Background</bold> Following recovery from acute infection of COVID-19, there is a risk for long-term health sequelae such as permanent lung damage. <bold>Objective</bold> To investigate biomarkers in hospitalized COVID-19 patients after discharge from intensive care unit (ICU) and study their relation to lung function and imaging. <bold>Methods</bold> COVID-19 patients (n=43, 14 women, mean age 57), previously ICU-hospitalized, were investigated 4 and 10 months after discharge. For comparison, patients with idiopathic pulmonary fibrosis (IPF) (n=38, 9 women; mean age 74) and healthy controls (n=77, 38 women, mean age 56 years) were included. We performed proteomic analyses on serum samples using proximity extension assay. Parenchymal involvement on thoracic computed tomography (CT)-scans were assessed as absence or minor (< 5% of lung parenchyma) or moderate to severe (>5%). In addition, spirometry and 6-minute walking test (6MWT) was performed. <bold>Results</bold> ICU treated COVID-19 patients demonstrated a persistent increase in proteins related to inflammation (including Gal-1, IL8, TNFSF14, CXCL13, MCP-3) and remodeling (MMP7, VEGFA) 10 months after discharge. MMP7 correlated inversely with forced vital capacity (FVC)% predicted and 6MWD at 4 months and FVC%, total lung capacity (TLC)%, diffusion capacity for carbon monoxide (DLCO)% at 10 months. Furthermore, MMP7 correlated with parenchymal involvement at both time points, and was higher in patients with moderate to severe opacities at 10 months. <bold>Conclusions</bold> Our results support the evidence of persistent inflammatory and remodeling processes, parenchymal involvement and functional impact in patients previously hospitalized for COVID-19.