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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 areaApplication areaSample typeProducts
Infectious Diseases
Patient Stratification
Plasma
Olink Target 96

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.

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