Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia.
COVID-19
Community acquired pneumonia
Olink proximity extension assays
Sepsis
Septic shock
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
24 Feb 2023
24 Feb 2023
Historique:
received:
28
10
2022
accepted:
10
02
2023
entrez:
24
2
2023
pubmed:
25
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
COVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features. We measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients. We identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers. This study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
Sections du résumé
BACKGROUND
BACKGROUND
COVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.
METHODS
METHODS
We measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.
RESULTS
RESULTS
We identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.
CONCLUSIONS
CONCLUSIONS
This study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
Identifiants
pubmed: 36829233
doi: 10.1186/s12931-023-02364-y
pii: 10.1186/s12931-023-02364-y
pmc: PMC9950694
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
62Informations de copyright
© 2023. The Author(s).
Références
N Engl J Med. 1996 Jun 27;334(26):1697-702
pubmed: 8637514
Cell. 2020 Oct 1;183(1):158-168.e14
pubmed: 32979941
Clin Transl Immunology. 2020 Dec 14;9(12):e1224
pubmed: 33343897
Nat Rev Microbiol. 2022 May;20(5):270-284
pubmed: 35354968
Crit Care. 2021 Aug 5;25(1):281
pubmed: 34353339
Insights Imaging. 2021 Mar 11;12(1):34
pubmed: 33704615
Science. 2022 Mar 11;375(6585):1122-1127
pubmed: 35271343
Intensive Care Med. 2006 Jun;32(6):910-4
pubmed: 16570150
Nat Commun. 2022 Aug 22;13(1):4830
pubmed: 35995775
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
Lancet. 2021 Aug 14;398(10300):622-637
pubmed: 34217425
Nat Rev Dis Primers. 2016 Jun 30;2:16045
pubmed: 28117397
Sci Adv. 2020 Dec 9;6(50):
pubmed: 33187979
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Nature. 2021 Mar;591(7848):124-130
pubmed: 33494096
Trends Mol Med. 2014 Apr;20(4):195-203
pubmed: 24581450
Am J Respir Crit Care Med. 2019 Apr 15;199(8):980-986
pubmed: 30365341
Nat Commun. 2021 Aug 9;12(1):4888
pubmed: 34373466
Ann Emerg Med. 2022 Oct;80(4):314-316
pubmed: 35461721
Sci Immunol. 2020 Aug 21;5(50):
pubmed: 32826343
Science. 1997 Apr 4;276(5309):60-6
pubmed: 9082986
Cell Rep Med. 2021 May 18;2(5):100287
pubmed: 33969320
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
PLoS Pathog. 2022 Sep 19;18(9):e1010819
pubmed: 36121875
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):
pubmed: 33479167
Front Immunol. 2020 Sep 16;11:575890
pubmed: 33042158
Crit Care. 2016 Apr 20;20(Suppl 2):94
pubmed: 27885969
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Lancet Respir Med. 2021 Jun;9(6):622-642
pubmed: 33965003
EMBO Mol Med. 2020 Apr 7;12(4):e10128
pubmed: 32176432
Nat Commun. 2022 Feb 17;13(1):946
pubmed: 35177642
Scand J Immunol. 2022 Jun 2;:e13195
pubmed: 35652743
J Gastroenterol Hepatol. 1991 Sep-Oct;6(5):509-19
pubmed: 1834243
Pathobiology. 2021;88(1):15-27
pubmed: 33049751
N Engl J Med. 2020 Dec 17;383(25):2451-2460
pubmed: 32412710
Signal Transduct Target Ther. 2021 Oct 27;6(1):372
pubmed: 34707085
Blood. 2019 Jun 13;133(24):2559-2569
pubmed: 30975637
BMC Infect Dis. 2019 Nov 5;19(1):931
pubmed: 31690258
Med (N Y). 2021 Oct 08;2(10):1163-1170.e2
pubmed: 34568856
Front Microbiol. 2020 Jul 23;11:1639
pubmed: 32793149
Nucleic Acids Res. 2021 Jan 8;49(D1):D605-D612
pubmed: 33237311
Am J Respir Crit Care Med. 2009 Oct 1;180(7):640-8
pubmed: 19590022
Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):
pubmed: 34548411
Cell Syst. 2020 Jul 22;11(1):11-24.e4
pubmed: 32619549
Thromb Haemost. 2012 Apr;107(4):656-61
pubmed: 22318499
Nat Med. 2020 Jul;26(7):1017-1032
pubmed: 32651579
Lancet Respir Med. 2020 Dec;8(12):1233-1244
pubmed: 33075298
Cell. 2022 Mar 3;185(5):916-938.e58
pubmed: 35216673
Thromb Haemost. 2015 Apr;113(4):686-97
pubmed: 25652913
Crit Care Med. 1996 Sep;24(9):1431-40
pubmed: 8797612
Crit Care Med. 2010 Feb;38(2 Suppl):S26-34
pubmed: 20083910
Lancet. 2022 Jul 30;400(10349):359-368
pubmed: 35908569
Clin Infect Dis. 2022 Jan 29;74(2):254-262
pubmed: 34013339
Immunity. 2020 Nov 17;53(5):1108-1122.e5
pubmed: 33128875
Cell. 2020 Jul 9;182(1):59-72.e15
pubmed: 32492406
Clin Transl Immunology. 2021 Jul 05;10(7):e1306
pubmed: 34257967
Nat Med. 2020 Oct;26(10):1636-1643
pubmed: 32839624
J Biol Chem. 2017 Nov 17;292(46):18848-18861
pubmed: 28939773
SAGE Open Med. 2019 Mar 21;7:2050312119835043
pubmed: 30915218
Sci Immunol. 2020 Sep 28;5(51):
pubmed: 32989174
JAMA. 2021 Aug 10;326(6):499-518
pubmed: 34228774
Nature. 2020 Jul;583(7816):437-440
pubmed: 32434211
Diagnostics (Basel). 2021 Jul 13;11(7):
pubmed: 34359331