Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients.
COVID-19
Inflammaging
Tocilizumab
interleukin-6
microRNA
Journal
Mechanisms of ageing and development
ISSN: 1872-6216
Titre abrégé: Mech Ageing Dev
Pays: Ireland
ID NLM: 0347227
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
28
08
2020
revised:
18
11
2020
accepted:
07
12
2020
pubmed:
12
12
2020
medline:
13
1
2021
entrez:
11
12
2020
Statut:
ppublish
Résumé
Current COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. The most amount of the death toll is accounted by old people affected by age-related diseases that develop a hyper-inflammatory syndrome. In this regard, we hypothesized that COVID-19 severity may be linked to inflammaging. Here, we examined 30 serum samples from patients enrolled in the clinical trial NCT04315480 assessing the clinical response to a single-dose intravenous infusion of the anti-IL-6 receptor drug Tocilizumab (TCZ) in COVID-19 patients with multifocal interstitial pneumonia. In these serum samples, as well as in 29 age- and gender-matched healthy control subjects, we assessed a set of microRNAs that regulate inflammaging, i.e. miR-146a-5p, miR-21-5p, and miR-126-3p, which were quantified by RT-PCR and Droplet Digital PCR. We showed that COVID-19 patients who did not respond to TCZ have lower serum levels of miR-146a-5p after the treatment (p = 0.007). Among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p = 0.008). Our data show that a blood-based biomarker, such as miR-146a-5p, can provide clues about the molecular link between inflammaging and COVID-19 clinical course, thus allowing to better understand the use of biologic drug armory against this worldwide health threat.
Identifiants
pubmed: 33307107
pii: S0047-6374(20)30209-8
doi: 10.1016/j.mad.2020.111413
pmc: PMC7722494
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
Circulating MicroRNA
0
MIRN146 microRNA, human
0
MicroRNAs
0
tocilizumab
I031V2H011
Banques de données
ClinicalTrials.gov
['NCT04315480']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
111413Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Références
Int J Biol Sci. 2020 Jun 27;16(13):2382-2391
pubmed: 32760206
Lancet. 2020 May 30;395(10238):1695-1704
pubmed: 32401715
Lancet. 2020 Apr 11;395(10231):1225-1228
pubmed: 32178769
Lancet. 2020 May 2;395(10234):1417-1418
pubmed: 32325026
Lancet Oncol. 2012 Jun;13(6):e249-58
pubmed: 22652233
Front Immunol. 2019 Feb 04;10:85
pubmed: 30778349
Front Immunol. 2016 Dec 19;7:604
pubmed: 28066415
Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975
pubmed: 32350134
Mol Cell Biol. 1990 May;10(5):2327-34
pubmed: 2183031
Sci Rep. 2019 Mar 6;9(1):3765
pubmed: 30842487
Physiol Rev. 2020 Oct 30;:
pubmed: 33124941
Ann Rheum Dis. 2020 Sep;79(9):1143-1151
pubmed: 32719045
Oxid Med Cell Longev. 2018 Jul 18;2018:7671850
pubmed: 30116492
FASEB J. 2018 Aug;32(8):4070-4084
pubmed: 29565737
Mech Ageing Dev. 2019 Jun;180:1-10
pubmed: 30880174
Oncotarget. 2015 Jun 10;6(16):14545-55
pubmed: 26036630
Exp Ther Med. 2019 Oct;18(4):3078-3084
pubmed: 31572547
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
PLoS One. 2012;7(12):e52782
pubmed: 23285182
J Med Virol. 2020 Jul;92(7):814-818
pubmed: 32253759
Front Immunol. 2015 Jan 29;6:19
pubmed: 25688245
EMBO J. 1990 Jun;9(6):1897-906
pubmed: 2112087
J Extracell Vesicles. 2020 Feb 18;9(1):1725285
pubmed: 32158519
BioDrugs. 2020 Aug;34(4):415-422
pubmed: 32557214
Int J Mol Sci. 2016 Jan 09;17(1):
pubmed: 26761003
Blood. 2020 Jun 18;135(25):2235-2251
pubmed: 32384151
Inflammation. 2015 Oct;38(5):1761-8
pubmed: 25805648
Intensive Care Med. 2020 May;46(5):846-848
pubmed: 32125452
Age (Dordr). 2013 Aug;35(4):1157-72
pubmed: 22692818
J Clin Pharmacol. 2020 Sep;60(9):1131-1146
pubmed: 32557541
Front Immunol. 2020 Apr 29;11:566
pubmed: 32411123
J Exp Med. 2011 Jun 6;208(6):1189-201
pubmed: 21555486
Cytokine Growth Factor Rev. 2020 Jun;53:33-37
pubmed: 32389499
Front Neurosci. 2020 Apr 03;14:311
pubmed: 32317924
Front Genet. 2013 Jun 26;4:121
pubmed: 23805154
Sci Rep. 2016 Dec 06;6:38339
pubmed: 27922090
Nat Med. 2020 Jul;26(7):1070-1076
pubmed: 32514174
Mech Ageing Dev. 2012 Nov-Dec;133(11-12):675-85
pubmed: 23041385
Eur Radiol. 2020 Aug;30(8):4407-4416
pubmed: 32215691
Blood. 2020 Jan 16;135(3):167-180
pubmed: 31805184
J Autoimmun. 2020 Jul;111:102452
pubmed: 32291137
Age (Dordr). 2013 Apr;35(2):419-29
pubmed: 22174010