Discrimination of COVID-19 From Inflammation-Induced Cytokine Storm Syndromes Using Disease-Related Blood Biomarkers.
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers
/ blood
COVID-19
/ blood
Cytokine Release Syndrome
/ blood
Diagnosis, Differential
Female
Humans
Interleukin-18
/ blood
Interleukin-8
/ blood
Lymphohistiocytosis, Hemophagocytic
/ blood
Macrophage Activation Syndrome
/ blood
Male
Middle Aged
Young Adult
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
20
11
2020
accepted:
06
04
2021
pubmed:
22
4
2021
medline:
13
10
2021
entrez:
21
4
2021
Statut:
ppublish
Résumé
Infection with the novel coronavirus SARS-CoV-2 triggers severe illness with high mortality in a subgroup of patients. Such a critical course of COVID-19 is thought to be associated with the development of cytokine storm, a condition seen in macrophage activation syndrome (MAS) and secondary hemophagocytic lymphohistiocytosis (HLH). However, specific data demonstrating a clear association of cytokine storm with severe COVID-19 are still lacking. The aim of this study was to directly address whether immune activation in COVID-19 does indeed mimic the conditions found in these classic cytokine storm syndromes. Levels of 22 biomarkers were quantified in serum samples from patients with COVID-19 (n = 30 patients, n = 83 longitudinal samples in total), patients with secondary HLH/MAS (n = 50), and healthy controls (n = 9). Measurements were performed using bead array assays and single-marker enzyme-linked immunosorbent assay. Serum biomarker levels were assessed for correlations with disease outcome. In patients with secondary HLH/MAS, we observed pronounced activation of the interleukin-18 (IL-18)-interferon-γ axis, increased serum levels of IL-1 receptor antagonist, intercellular adhesion molecule 1, and IL-8, and strongly reduced levels of soluble Fas ligand in the course of SARS-CoV-2 infection. These observations appeared to discriminate immune dysregulation in critical COVID-19 from the well-recognized characteristics of other cytokine storm syndromes. Serum biomarker profiles clearly separate COVID-19 from MAS or secondary HLH in terms of distinguishing the severe systemic hyperinflammation that occurs following SARS-CoV-2 infection. These findings could be useful in determining the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID-19.
Identifiants
pubmed: 33880885
doi: 10.1002/art.41763
pmc: PMC8251089
doi:
Substances chimiques
Biomarkers
0
Interleukin-18
0
Interleukin-8
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1791-1799Subventions
Organisme : European Union's Horizon 2020 research and innovation program
ID : 779295
Organisme : Deutsche Forschungsgemeinschaft
ID : FO 354/14-1
Informations de copyright
© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
Références
N Engl J Med. 2020 May 7;382(19):1811-1822
pubmed: 32374962
Lancet Respir Med. 2021 Mar;9(3):295-304
pubmed: 33493450
Arthritis Rheumatol. 2020 Jul;72(7):1059-1063
pubmed: 32293098
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):18951-18953
pubmed: 32699149
Blood. 2020 Jul 30;136(5):542-552
pubmed: 32356861
Ann Rheum Dis. 2021 Jan;80(1):3-5
pubmed: 33203641
Ann Rheum Dis. 2017 Jan;76(1):166-172
pubmed: 27296321
Crit Care. 2020 Dec 10;24(1):688
pubmed: 33302991
JCI Insight. 2021 Jan 11;6(1):
pubmed: 33232303
J Allergy Clin Immunol. 2020 Jul;146(1):213-215
pubmed: 32437739
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
Signal Transduct Target Ther. 2020 Dec 24;5(1):293
pubmed: 33361764
J Clin Immunol. 2021 Apr;41(3):658-665
pubmed: 33417087
Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):602-11
pubmed: 8810593
JAMA Intern Med. 2020 Sep 1;180(9):1152-1154
pubmed: 32602883
JAMA. 2020 Oct 6;324(13):1307-1316
pubmed: 32876695
Arthritis Rheumatol. 2018 Aug;70(8):1319-1330
pubmed: 29609200
Rheumatology (Oxford). 2016 Dec;55(12):2237-2247
pubmed: 27616144
Proc Natl Acad Sci U S A. 1997 May 27;94(11):5860-5
pubmed: 9159165
JAMA. 2012 Jun 20;307(23):2526-33
pubmed: 22797452
Front Immunol. 2019 Feb 01;10:119
pubmed: 30774631
Lancet Respir Med. 2020 Dec;8(12):1233-1244
pubmed: 33075298
JCI Insight. 2020 Sep 3;5(17):
pubmed: 32687484
Autoimmun Rev. 2021 Feb;20(2):102726
pubmed: 33326855
Nat Med. 2020 Oct;26(10):1636-1643
pubmed: 32839624
Science. 2020 Aug 7;369(6504):718-724
pubmed: 32661059
Annu Rev Immunol. 2009;27:519-50
pubmed: 19302047
Lancet Rheumatol. 2020 Jun;2(6):e325-e331
pubmed: 32501454