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

Kalafatis, Dimitrios LU ; Björnson, Mikael LU ; Svobodová, Barbora LU ; Kistner, Anna ; Nygren-Bonnier, Malin ; Runold, Michael ; Bruchfeld, Judith ; Wheelock, Åsa ; Dellgren, Göran and Elowsson, Linda LU , et al. (2025) In ERJ open research 11(3). p.1-13
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 intensive care unit (ICU)-treated patients with COVID-19 (n=43) at 4 and 10 months post hospitalisation.

RESULTS: 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 (
... (More)

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 intensive care unit (ICU)-treated patients with COVID-19 (n=43) at 4 and 10 months post hospitalisation.

RESULTS: 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.

CONCLUSION: 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ERJ open research
volume
11
issue
3
pages
1 - 13
publisher
European Respiratory Society
external identifiers
  • scopus:105009073540
  • pmid:40551787
ISSN
2312-0541
DOI
10.1183/23120541.00981-2024
language
English
LU publication?
yes
additional info
Copyright ©The authors 2025.
id
a90f6a41-90c9-48ee-941b-27cc6776360e
date added to LUP
2025-06-30 16:30:10
date last changed
2025-07-07 04:02:16
@article{a90f6a41-90c9-48ee-941b-27cc6776360e,
  abstract     = {{<p>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).</p><p>METHODS: 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.</p><p>RESULTS: Four months post discharge, patients with COVID-19 demonstrated lower % predicted forced vital capacity (72.2%<br>
 versus 113% (p&lt;0.0001)) and % predicted forced expiratory volume in 1 s (74.5%<br>
 versus 103% (p&lt;0.0001)) compared with healthy controls. A persistent upregulation (<br>
 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 (&gt;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 (&lt;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.<br>
 </p><p>CONCLUSION: 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.</p>}},
  author       = {{Kalafatis, Dimitrios and Björnson, Mikael and Svobodová, Barbora and Kistner, Anna and Nygren-Bonnier, Malin and Runold, Michael and Bruchfeld, Judith and Wheelock, Åsa and Dellgren, Göran and Elowsson, Linda and Westergren-Thorsson, Gunilla and Sköld, Magnus}},
  issn         = {{2312-0541}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{1--13}},
  publisher    = {{European Respiratory Society}},
  series       = {{ERJ open research}},
  title        = {{Protein profiling in intensive care unit-treated COVID-19 patients identifies biomarkers of residual lung abnormalities}},
  url          = {{http://dx.doi.org/10.1183/23120541.00981-2024}},
  doi          = {{10.1183/23120541.00981-2024}},
  volume       = {{11}},
  year         = {{2025}},
}