Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients.
Adult
Aged
Aged, 80 and over
Biomarkers
/ blood
COVID-19
/ blood
Critical Care
Cytokine Release Syndrome
/ blood
Female
Humans
Intensive Care Units
Interleukin-6
/ blood
Iran
Male
Middle Aged
Pilot Projects
Receptors, Tumor Necrosis Factor, Type I
/ blood
SARS-CoV-2
Severity of Illness Index
Tumor Necrosis Factor-alpha
/ blood
ARDS
COVID-19
TNF-α
cytokine storm
soluble TNF-α
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
24
08
2020
accepted:
31
03
2021
entrez:
10
5
2021
pubmed:
11
5
2021
medline:
21
5
2021
Statut:
epublish
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm. To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity. We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR. The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.
Sections du résumé
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm.
Objectives
To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity.
Methods
We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran.
Results
Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR.
Conclusions
The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.
Identifiants
pubmed: 33968010
doi: 10.3389/fimmu.2021.592727
pmc: PMC8100036
doi:
Substances chimiques
Biomarkers
0
IL6 protein, human
0
Interleukin-6
0
Receptors, Tumor Necrosis Factor, Type I
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
592727Subventions
Organisme : Medical Research Council
ID : MR/T010371/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021 Mortaz, Tabarsi, Jamaati, Dalil Roofchayee, Dezfuli, Hashemian, Moniri, Marjani, Malekmohammad, Mansouri, Varahram, Folkerts and Adcock.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Clin Invest. 2020 May 1;130(5):2620-2629
pubmed: 32217835
Blood. 2014 Jul 10;124(2):188-95
pubmed: 24876563
PLoS One. 2015 Mar 30;10(3):e0122073
pubmed: 25823004
JAMA. 2020 Mar 17;323(11):1061-1069
pubmed: 32031570
Cancer Immunol Res. 2016 May;4(5):441-51
pubmed: 26896171
Cytokine Growth Factor Rev. 2020 Jun;53:66-70
pubmed: 32418715
Virus Res. 2008 Apr;133(1):13-9
pubmed: 17374415
Clin Rheumatol. 2020 Jul;39(7):2085-2094
pubmed: 32474885
Front Immunol. 2020 May 01;11:827
pubmed: 32425950
J Clin Invest. 2012 Nov;122(11):4094-104
pubmed: 23064360
J Immunol. 1991 Dec 15;147(12):4229-38
pubmed: 1661312
Circ Heart Fail. 2014 Jan;7(1):5-11
pubmed: 24323631
J Am Coll Cardiol. 2000 Aug;36(2):523-8
pubmed: 10933367
Nat Rev Cardiol. 2020 Sep;17(9):543-558
pubmed: 32690910
Cell Mol Immunol. 2020 Aug;17(8):878-880
pubmed: 32587367
Nat Med. 2020 Apr;26(4):453-455
pubmed: 32284614
Lymphokine Cytokine Res. 1992 Jun;11(3):157-9
pubmed: 1327192
Immunity. 1999 Dec;11(6):783-93
pubmed: 10626900
Cell Host Microbe. 2020 Jun 10;27(6):863-869
pubmed: 32464098
Emerg Microbes Infect. 2020 Dec;9(1):1123-1130
pubmed: 32475230
J Biol Chem. 2008 May 23;283(21):14177-81
pubmed: 18385130
Rheumatology (Oxford). 2010 Jul;49(7):1215-28
pubmed: 20194223
J Clin Invest. 2020 May 1;130(5):2202-2205
pubmed: 32217834
Immunity. 2005 Jan;22(1):93-104
pubmed: 15664162
Cell Death Differ. 2020 Nov;27(11):3196-3207
pubmed: 32514047
Cytokine X. 2020 Jun;2(2):100029
pubmed: 32421092
Clin Immunol. 2020 Jun;215:108427
pubmed: 32325252
Eur J Immunol. 2010 Dec;40(12):3347-57
pubmed: 21110318
Am J Respir Crit Care Med. 2020 Sep 15;202(6):812-821
pubmed: 32584597
Nat Rev Immunol. 2020 Jun;20(6):363-374
pubmed: 32346093