Protein profiling in intensive care unit-treated COVID-19 patients identifies biomarkers of residual lung abnormalities
ERJ Open Research, 2025
Kalafatis D., Björnson M., Svobodová B., Kistner A., Nygren-Bonnier M., Runold M., Bruchfeld J., Wheelock ?., Dellgren G., Elowsson L., Westergren-Thorsson G., Sköld M.
Disease area | Application area | Sample type | Products |
---|---|---|---|
Infectious Diseases | Patient Stratification | Plasma | Olink Target 96 |
Abstract
Background
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).
Methods
We performed multiplex profiling of serum and collected clinical data from previously intensive care unit (ICU)-treated COVID-19 patients (n=43) at four and ten months post hospitalization.
Results
Four months post discharge, COVID-19 patients demonstrated lower % predicted forced vital capacity (FVC%) (72.2%versus113% (p<0.0001) and % predicted forced expiratory volume in 1 s (FEV1%) (74.5%versus103% (p<0.0001) compared to healthy controls. A persistent upregulation (versushealthy controls) of inflammatory and remodeling factors including among others, Gal-1, CXCL13, MCP-3 and 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 LAMP3 and MMP7 compared to patients with minor (< 5%) or no findings on HRCT. Moreover, both proteins demonstrated consecutive associations to lung function and parenchymal involvement. Histological evaluation of LAMP3 in lung tissue confirmed LAMP3 localization to alveolar type 2 (AT2) cells in more preserved areas of the parenchyma. However, areas of remodeling were devoid of LAMP3 concurrent with appearance of KRT5+ and KRT17+ basal cells.
Conclusion
Despite functional and radiological improvements following COVID-19, persistent upregulation of inflammation and remodeling factors were observed. Similarities in the expression of LAMP3 in COVID-19 and IPF may suggest it as a potential biomarker for chronic lung damage.