Serum proteomic profiling identifies transforming growth factor β receptor as a marker of persistent symptoms up to 18 months after mild SARS-CoV-2 infection.
8 affiliations
- 1Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, Norway.
- 2Institute of Clinical Medicine, University of Oslo, Norway.
- 3Influenza Centre, University of Bergen, Norway.
- 4Department of Clinical Science, University of Bergen, Norway.
- 5Department of Microbiology, Haukeland University Hospital, Norway.
- 6Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
- 7National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway.
- 8Norwegian Institute of Public Health, Oslo, Norway.
Abstract
Persistent symptoms following the acute phase of SARS-CoV-2 infection have emerged as an increasing health problem. The pathogenesis for the development of post-COVID Condition (PCC) is still elusive. Herein we included serum samples from non-hospitalized (n = 189) and hospitalized (n = 52) COVID-19 patients, representing approximately 90% of all patients with confirmed SARS-CoV-2 infection in the municipality of Bergen, Norway between 28 February and 4 April 2020. The patients were followed clinically with systematic interviews for up to 18 months. Accompanying serum samples were analyzed by un-targeted proteomics and enzyme immunoassay (EIA). Our major findings were: (i) In a subpopulation of the total cohort (n = 69) proteome analyses identified 28 proteins that were dysregulated in individuals with mild and moderate PCC. Pathway analyses suggested the involvement of cell adhesion, extracellular matrix remodeling and immunity. (ii) The most significant finding were elevated serum levels of transforming growth factor β receptor 2 (TGFBR2) that were significantly higher in those with moderate as compared with those with mild and those without any PCC symptoms. (iii) This finding was conformed in the total cohort as assessed by EIA. (iv) The strongest association for TGFBR2 was found for impaired cognition that was seen at both 6, 12 and 18 months after infection. (v) In contrast to the home-isolated patients, no association of TGFBR2 to PCC symptoms were seen for those that were hospitalized during the acute infection. Our finding may indicate the involvement of TGFBR2 related pathways in the pathogenesis of PCC, in particular in those with cognitive symptoms.
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BibTeX
@article{ueland2026serum,
title = {{Serum proteomic profiling identifies transforming growth factor β receptor as a marker of persistent symptoms up to 18 months after mild SARS-CoV-2 infection.}},
author = {Thor Ueland and Rebecca Jane Cox and Annika E Michelsen and Elisabeth Berg Fjelltveit and Kuan Yang and Anders Bonnevie and Tuva Dahl and Fan Zhou and Pål Aukrust and Bjørn Blomberg and Kari Otterdal and Bente Halvorsen and Nina Langeland},
journal = {Brain, behavior, \& immunity - health},
year = {2026},
month = oct,
doi = {10.1016/j.bbih.2026.101396},
url = {https://europepmc.org/article/MED/42999630},
note = {CC BY},
}
RIS
TY - JOUR
TI - Serum proteomic profiling identifies transforming growth factor β receptor as a marker of persistent symptoms up to 18 months after mild SARS-CoV-2 infection.
AU - Thor Ueland
AU - Rebecca Jane Cox
AU - Annika E Michelsen
AU - Elisabeth Berg Fjelltveit
AU - Kuan Yang
AU - Anders Bonnevie
AU - Tuva Dahl
AU - Fan Zhou
AU - Pål Aukrust
AU - Bjørn Blomberg
AU - Kari Otterdal
AU - Bente Halvorsen
AU - Nina Langeland
PY - 2026
DA - 2026/10/22
JO - Brain, behavior, & immunity - health
DO - 10.1016/j.bbih.2026.101396
UR - https://europepmc.org/article/MED/42999630
AB - Persistent symptoms following the acute phase of SARS-CoV-2 infection have emerged as an increasing health problem. The pathogenesis for the development of post-COVID Condition (PCC) is still elusive. Herein we included serum samples from non-hospitalized (n = 189) and hospitalized (n = 52) COVID-19 patients, representing approximately 90% of all patients with confirmed SARS-CoV-2 infection in the municipality of Bergen, Norway between 28 February and 4 April 2020. The patients were followed clinically with systematic interviews for up to 18 months. Accompanying serum samples were analyzed by un-targeted proteomics and enzyme immunoassay (EIA). Our major findings were: (i) In a subpopulation of the total cohort (n = 69) proteome analyses identified 28 proteins that were dysregulated in individuals with mild and moderate PCC. Pathway analyses suggested the involvement of cell adhesion, extracellular matrix remodeling and immunity. (ii) The most significant finding were elevated serum levels of transforming growth factor β receptor 2 (TGFBR2) that were significantly higher in those with moderate as compared with those with mild and those without any PCC symptoms. (iii) This finding was conformed in the total cohort as assessed by EIA. (iv) The strongest association for TGFBR2 was found for impaired cognition that was seen at both 6, 12 and 18 months after infection. (v) In contrast to the home-isolated patients, no association of TGFBR2 to PCC symptoms were seen for those that were hospitalized during the acute infection. Our finding may indicate the involvement of TGFBR2 related pathways in the pathogenesis of PCC, in particular in those with cognitive symptoms.
SN - 2666-3546
ER -