The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19.
COVID-19
IL-1β
IL-6
PASC
SARS-CoV-2
TNF
cytokine
long covid
macrophage
post-acute sequelae of COVID-19
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
21 06 2022
21 06 2022
Historique:
received:
11
01
2022
revised:
28
03
2022
accepted:
25
05
2022
entrez:
22
6
2022
pubmed:
23
6
2022
medline:
25
6
2022
Statut:
ppublish
Résumé
Post-acute sequelae of COVID-19 (PASC) is emerging as global problem with unknown molecular drivers. Using a digital epidemiology approach, we recruited 8,077 individuals to the cohort study for digital health research in Germany (DigiHero) to respond to a basic questionnaire followed by a PASC-focused survey and blood sampling. We report the first 318 participants, the majority thereof after mild infections. Of those, 67.8% report PASC, predominantly consisting of fatigue, dyspnea, and concentration deficit, which persists in 60% over the mean 8-month follow-up period and resolves independently of post-infection vaccination. PASC is not associated with autoantibodies, but with elevated IL-1β, IL-6, and TNF plasma levels, which we confirm in a validation cohort with 333 additional participants and a longer time from infection of 10 months. Blood profiling and single-cell data from early infection suggest the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop.
Identifiants
pubmed: 35732153
pii: S2666-3791(22)00195-1
doi: 10.1016/j.xcrm.2022.100663
pmc: PMC9214726
pii:
doi:
Substances chimiques
Cytokines
0
IL1B protein, human
0
IL6 protein, human
0
Interleukin-1beta
0
Interleukin-6
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
100663Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Front Immunol. 2020 Oct 15;11:584241
pubmed: 33178218
Nat Immunol. 2020 Dec;21(12):1506-1516
pubmed: 33028979
Mayo Clin Proc. 2022 Mar;97(3):454-464
pubmed: 35135695
Cell. 2021 Dec 22;184(26):6243-6261.e27
pubmed: 34914922
New Sci. 2021 Mar 13;249(3325):9
pubmed: 33746325
Front Immunol. 2014 Oct 07;5:491
pubmed: 25339958
PLoS One. 2022 Feb 22;17(2):e0262911
pubmed: 35192635
Biol Psychiatry. 2006 May 1;59(9):775-85
pubmed: 16458261
N Engl J Med. 2021 Apr 22;384(16):1491-1502
pubmed: 33631065
Nature. 2021 Jul;595(7866):283-288
pubmed: 34010947
Sci Rep. 2016 Aug 25;6:31959
pubmed: 27558590
Int J Biol Sci. 2012;8(9):1237-47
pubmed: 23136552
J Infect Dis. 2021 Dec 1;224(11):1839-1848
pubmed: 34677601
Emerg Infect Dis. 2020 Aug;26(8):1834-1838
pubmed: 32383638
Front Cell Infect Microbiol. 2021 Mar 30;11:596201
pubmed: 33859951
Front Immunol. 2022 May 09;13:876306
pubmed: 35615365
Clin Rheumatol. 2021 Jul;40(7):2611-2619
pubmed: 33733315
Mol Psychiatry. 2008 Jul;13(7):717-28
pubmed: 17700577
Med (N Y). 2020 Dec 18;1(1):90-102
pubmed: 33294881
EBioMedicine. 2021 Feb;64:103230
pubmed: 33530000
Nat Med. 2021 Apr;27(4):626-631
pubmed: 33692530
Nat Med. 2021 May;27(5):904-916
pubmed: 33879890
Mol Pharm. 2021 Mar 1;18(3):754-771
pubmed: 33464914
Mucosal Immunol. 2022 Mar;15(3):515-524
pubmed: 35288643
Nat Med. 2020 Jun;26(6):842-844
pubmed: 32398875
Cochrane Database Syst Rev. 2022 Jan 26;1:CD015308
pubmed: 35080773
Front Microbiol. 2021 Jun 23;12:698169
pubmed: 34248921
Nature. 2022 Mar;603(7902):587-598
pubmed: 35090163
Clin Infect Dis. 2022 Apr 9;74(7):1191-1198
pubmed: 34223884
Cochrane Database Syst Rev. 2021 Mar 18;3:CD013881
pubmed: 33734435
Clin Med Insights Arthritis Musculoskelet Disord. 2020 Dec 3;13:1179544120978667
pubmed: 33328777
Endocr Pract. 2020 Oct;26(10):1166-1172
pubmed: 33471718
Am J Trop Med Hyg. 2020 Jul;103(1):69-72
pubmed: 32446312
Biol Psychiatry. 2019 Apr 15;85(8):679-689
pubmed: 30447911
J Clin Invest. 2001 Oct;108(8):1097-104
pubmed: 11602615
Clin Microbiol Infect. 2022 Apr;28(4):611.e9-611.e16
pubmed: 34763058
Lancet. 2021 Jan 16;397(10270):220-232
pubmed: 33428867
Gen Hosp Psychiatry. 2009 Jul-Aug;31(4):318-26
pubmed: 19555791
Curr Neuropharmacol. 2008 Sep;6(3):193-202
pubmed: 19506720
Lancet Healthy Longev. 2021 Jan;2(1):e34-e41
pubmed: 33521772
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
Front Immunol. 2022 Jan 10;12:746021
pubmed: 35082777
Nat Aging. 2021 Sep;1(9):769-782
pubmed: 34746804
Lancet Respir Med. 2021 Jun;9(6):622-642
pubmed: 33965003
Sci Immunol. 2021 Feb 23;6(56):
pubmed: 33622974
Nat Immunol. 2022 Feb;23(2):194-202
pubmed: 35105985
J Rehabil Med. 2020 May 25;52(5):jrm00063
pubmed: 32449782
Cell Rep Med. 2021 May 18;2(5):100269
pubmed: 33899032
JAMA. 2020 Aug 11;324(6):603-605
pubmed: 32644129
Nat Rev Immunol. 2016 Oct;16(10):626-38
pubmed: 27546235
Lancet Microbe. 2021 Jan;2(1):e13-e22
pubmed: 33521734
Cell Rep Med. 2021 Mar 16;2(3):100208
pubmed: 33564749
Immunity. 2020 Aug 18;53(2):442-455.e4
pubmed: 32668194
PLoS One. 2021 Aug 4;16(8):e0254347
pubmed: 34347785
Nat Rev Rheumatol. 2021 Jun;17(6):315-332
pubmed: 33903743
Curr Opin Virol. 2017 Apr;23:35-42
pubmed: 28319790
JAMA Netw Open. 2021 Oct 1;4(10):e2128568
pubmed: 34643720
J Neuroinflammation. 2010 Apr 16;7:27
pubmed: 20398373
Ann Rheum Dis. 2020 Dec;79(12):1661-1663
pubmed: 32581086
Nature. 2021 Mar;591(7851):639-644
pubmed: 33461210
Cell. 2022 Mar 3;185(5):881-895.e20
pubmed: 35216672
Cell. 2020 Dec 10;183(6):1479-1495.e20
pubmed: 33171100
J Clin Invest. 2021 Dec 15;131(24):
pubmed: 34710063
JAMA Intern Med. 2021 May 1;181(5):702-704
pubmed: 33180119
iScience. 2021 Jul 23;24(7):102752
pubmed: 34179733
Indian J Tuberc. 2021 Jul;68(3):330-333
pubmed: 34099197
Arthritis Rheum. 2008 Oct;58(10):2949-57
pubmed: 18821704
Lancet Diabetes Endocrinol. 2022 Mar;10(3):221-230
pubmed: 35114136
Nat Commun. 2021 Apr 9;12(1):2117
pubmed: 33837204
Nature. 2020 Dec;588(7837):315-320
pubmed: 32846427
Science. 2022 Mar 11;375(6585):1122-1127
pubmed: 35271343
PLoS One. 2021 Jun 17;16(6):e0252217
pubmed: 34138906
Sci Transl Med. 2020 Nov 18;12(570):
pubmed: 33139519
Eur Respir J. 2021 Apr 29;57(4):
pubmed: 33419891
J Neuroinflammation. 2016 Jun 07;13(1):141
pubmed: 27267059
Cell. 2020 Sep 17;182(6):1419-1440.e23
pubmed: 32810438
Nat Immunol. 2022 Feb;23(2):210-216
pubmed: 35027728
Nat Biotechnol. 2020 Aug;38(8):970-979
pubmed: 32591762
EMBO Mol Med. 2021 Aug 9;13(8):e14150
pubmed: 34133077
J Clin Invest. 2021 Oct 15;131(20):
pubmed: 34437303
Brain Res Rev. 2009 Apr;60(1):57-64
pubmed: 19166877
Immunity. 2021 Jul 13;54(7):1463-1477.e11
pubmed: 34115964
Immunity. 2020 Sep 15;53(3):487-495
pubmed: 32853545
Thorax. 2021 Apr;76(4):399-401
pubmed: 33273026
Nature. 2021 Jul;595(7865):107-113
pubmed: 33915569
Brain Behav Immun. 2010 Oct;24(7):1074-7
pubmed: 20227485
Curr Opin Rheumatol. 2021 Mar 1;33(2):155-162
pubmed: 33332890
Nat Med. 2021 Apr;27(4):601-615
pubmed: 33753937
Sci Immunol. 2021 Aug 19;6(62):
pubmed: 34413139
Lancet Respir Med. 2021 Nov;9(11):1275-1287
pubmed: 34627560
BMC Neurol. 2011 Mar 24;11:37
pubmed: 21435231
Nat Med. 2020 Oct;26(10):1636-1643
pubmed: 32839624
J Neurosci. 2012 Oct 3;32(40):13896-905
pubmed: 23035099
Pharmacol Res. 2019 Nov;149:104402
pubmed: 31536783
Nature. 2021 Dec;600(7889):530-535
pubmed: 34670266
iScience. 2021 Nov 19;24(11):103325
pubmed: 34723157