A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity.
COVID-19
Innate immunity
Molecular biology
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
08 10 2021
08 10 2021
Historique:
received:
26
05
2021
accepted:
25
08
2021
pubmed:
28
8
2021
medline:
28
10
2021
entrez:
27
8
2021
Statut:
epublish
Résumé
BACKGROUNDSARS-CoV-2 infection induces mucin overexpression, further promoting disease. Given that mucins are critical components of innate immunity, unraveling their expression profiles that dictate the course of disease could greatly enhance our understanding and management of COVID-19.METHODSUsing validated RT-PCR assays, we assessed mucin mRNA expression in the blood of patients with symptomatic COVID-19 compared with symptomatic patients without COVID-19 and healthy controls and correlated the data with clinical outcome parameters. Additionally, we analyzed mucin expression in mucus and lung tissue from patients with COVID-19 and investigated the effect of drugs for COVID-19 treatment on SARS-CoV-2-induced mucin expression in pulmonary epithelial cells.RESULTSWe identified a dynamic blood mucin mRNA signature that clearly distinguished patients with symptomatic COVID-19 from patients without COVID-19 based on expression of MUC1, MUC2, MUC4, MUC6, MUC13, MUC16, and MUC20 (AUCROC of 91.8%; sensitivity and specificity of 90.6% and 93.3%, respectively) and that discriminated between mild and critical COVID-19 based on the expression of MUC16, MUC20, and MUC21 (AUCROC of 89.1%; sensitivity and specificity of 90.0% and 85.7%, respectively). Differences in the transcriptional landscape of mucins in critical cases compared with mild cases identified associations with COVID-19 symptoms, respiratory support, organ failure, secondary infections, and mortality. Furthermore, we identified different mucins in the mucus and lung tissue of critically ill COVID-19 patients and showed the ability of baricitinib, tocilizumab, favipiravir, and remdesivir to suppress expression of SARS-CoV-2-induced mucins.CONCLUSIONThis multifaceted blood mucin mRNA signature showed the potential role of mucin profiling in diagnosing, estimating severity, and guiding treatment options in patients with COVID-19.FUNDINGThe Antwerp University Research and the Research Foundation Flanders COVID-19 funds.
Identifiants
pubmed: 34448730
pii: e151777
doi: 10.1172/jci.insight.151777
pmc: PMC8525642
doi:
pii:
Substances chimiques
Antiviral Agents
0
Mucins
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
J Pathol. 2012 Sep;228(1):67-76
pubmed: 22733568
Cell Res. 2020 Mar;30(3):269-271
pubmed: 32020029
PLoS One. 2017 Jul 14;12(7):e0181126
pubmed: 28708884
Gastroenterology. 1991 Jan;100(1):129-36
pubmed: 1983814
Thromb Res. 2020 Oct;194:222-228
pubmed: 33213847
Nat Med. 2021 Jan;27(1):28-33
pubmed: 33442016
Proteomics. 2018 Apr;18(7):e1700456
pubmed: 29436780
N Engl J Med. 2020 Dec 10;383(24):2333-2344
pubmed: 33085857
Comput Struct Biotechnol J. 2021;19:1-15
pubmed: 33312453
J Mol Med (Berl). 2006 Dec;84(12):1055-66
pubmed: 17058067
Lancet Infect Dis. 2020 Jun;20(6):697-706
pubmed: 32224310
Nat Biotechnol. 2020 Aug;38(8):970-979
pubmed: 32591762
Open Forum Infect Dis. 2020 Dec 21;8(1):ofaa578
pubmed: 33447639
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
J Biol Chem. 2001 May 25;276(21):18327-36
pubmed: 11278439
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3970-5
pubmed: 19234122
Nat Rev Cancer. 2009 Dec;9(12):874-85
pubmed: 19935676
Front Immunol. 2018 Jun 28;9:1510
pubmed: 30002661
PLoS One. 2013;8(3):e59327
pubmed: 23527164
Sci Rep. 2021 Mar 29;11(1):7052
pubmed: 33782412
Physiol Rep. 2021 Jan;9(1):e14701
pubmed: 33373502
Protein Cell. 2020 Sep;11(9):680-687
pubmed: 32671793
J Med Virol. 2021 Feb;93(2):582-584
pubmed: 32776556
Infect Immun. 2014 Aug;82(8):3227-39
pubmed: 24866791
Lancet Infect Dis. 2021 Jun;21(6):e145
pubmed: 33301728
J Clin Med. 2017 Nov 29;6(12):
pubmed: 29186029
J Hematol Oncol. 2008 May 28;1:2
pubmed: 18577250
N Engl J Med. 2021 Mar 4;384(9):795-807
pubmed: 33306283
Nat Med. 2020 Oct;26(10):1623-1635
pubmed: 32807934
Mucosal Immunol. 2008 May;1(3):183-97
pubmed: 19079178
Drug Des Devel Ther. 2019 Sep 24;13:3391-3404
pubmed: 31576113
Sci Adv. 2021 Jan 1;7(1):
pubmed: 33187978
JAMA. 2012 Jun 20;307(23):2526-33
pubmed: 22797452
Intern Emerg Med. 2021 Sep;16(6):1541-1545
pubmed: 33453011
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Nature. 2020 Dec;588(7837):315-320
pubmed: 32846427
J Crohns Colitis. 2020 Jul 30;14(7):974-994
pubmed: 32003421
Cells. 2020 Mar 25;9(4):
pubmed: 32218149
Intensive Care Med. 1996 Jul;22(7):707-10
pubmed: 8844239
Clin Chem. 2012 May;58(5):936-40
pubmed: 22205690
Proc Natl Acad Sci U S A. 2020 Oct 27;117(43):26955-26965
pubmed: 33037151
Immunology. 2003 Jan;108(1):32-41
pubmed: 12519300
Int J Surg. 2014 Dec;12(12):1495-9
pubmed: 25046131
PLoS One. 2020 May 4;15(5):e0232612
pubmed: 32365119
Immunology. 2004 Mar;111(3):291-7
pubmed: 15009429
Lancet Infect Dis. 2020 Jun;20(6):630-631
pubmed: 32240633
Cell Res. 2020 Dec;30(12):1078-1087
pubmed: 33159154
J Pediatr. 2020 Dec;227:45-52.e5
pubmed: 32827525
J Intern Med. 2008 Apr;263(4):432-9
pubmed: 18298483