Protein profiling in intensive care unit-treated COVID-19 patients identifies biomarkers of residual lung abnormalities

In this study, we combine proteomics with functional parameters and imaging to examine potential biomarkers that may identify patients at risk of developing persistent lung sequelae following coronavirus disease 2019 (COVID-19). We performed multiplex profiling of serum and collected clinical data from intensive care unit (ICU)-treated patients with COVID-19 (n=43) at 4 and 10 months post hospitalisation. Four months post discharge, patients with COVID-19 demonstrated lower % predicted forced vital capacity (72.2% versus 113% (p<0.0001)) and % predicted forced expiratory volume in 1 s (74.5% versus 103% (p<0.0001)) compared with healthy controls. A persistent upregulation (versus healthy controls) of inflammatory and remodelling factors, including among others, Galectin-1 (Gal-1), C-X-C motif chemokine 13 (CXCL13), monocyte chemoattractant protein 3 (MCP-3) and matrix metalloproteinase 7 (MMP7), were observed. Patients with moderate to severe parenchymal involvement (>5% of lung tissue) on high-resolution computed tomography (HRCT) had higher levels of the proteins lysosomal associated membrane protein-3 (LAMP3) and MMP7 compared with patients with minor (<5%) or no findings on HRCT. Both proteins demonstrated consecutive associations to lung function and parenchymal involvement. Histological evaluation of LAMP3 in lung tissue confirmed LAMP3 localisation to alveolar type 2 cells in more preserved areas of the parenchyma. However, areas of remodelling were devoid of LAMP3 concurrent with the appearance of KRT5+ and KRT17+ basal cells. Despite functional and radiological improvements following COVID-19, persistent upregulation of inflammation and remodelling factors were observed. Similarities in the expression of LAMP3 in COVID-19 and idiopathic pulmonary fibrosis may suggest it as a potential biomarker for chronic lung damage.