Observational cohort study of IP-10's potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
10
09
2020
accepted:
24
12
2020
entrez:
12
1
2021
pubmed:
13
1
2021
medline:
20
1
2021
Statut:
epublish
Résumé
Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking. In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation. Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications. Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making. Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.
Sections du résumé
BACKGROUND
Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking.
METHODS
In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation.
RESULTS
Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications.
CONCLUSIONS
Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.
Identifiants
pubmed: 33434221
doi: 10.1371/journal.pone.0245296
pii: PONE-D-20-27735
pmc: PMC7802954
doi:
Substances chimiques
Biomarkers
0
CXCL10 protein, human
0
Chemokine CXCL10
0
Banques de données
ClinicalTrials.gov
['NCT04389645']
Types de publication
Clinical Trial
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0245296Déclaration de conflit d'intérêts
Authors SL, TG, GSL, DL, EB, DD, AZ and AN declare they have no competing interests. Authors TIB, AA, LK, EB, RN, OB, YI, MR, AG, RK, ES, NA, MH, OZ, TMG, KO, and EE are employees of MeMed, the manufacturer of the platform used to measure IP-10, TRAIL, and CRP levels. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Références
JCI Insight. 2019 May 2;4(9):
pubmed: 31045578
Pediatrics. 2017 Oct;140(4):
pubmed: 28904072
PLoS One. 2017 Jan 3;12(1):e0169100
pubmed: 28046003
JAMA Intern Med. 2021 Jan 1;181(1):139-140
pubmed: 32744622
Lancet Infect Dis. 2017 Apr;17(4):431-440
pubmed: 28012942
Sci Immunol. 2020 May 8;5(47):
pubmed: 32385052
Nat Rev Immunol. 2020 May;20(5):277
pubmed: 32249847
Eur J Immunol. 2008 Aug;38(8):2168-79
pubmed: 18624292
Am J Respir Crit Care Med. 2013 Jan 1;187(1):65-77
pubmed: 23144331
JAMA. 2012 Jun 20;307(23):2526-33
pubmed: 22797452
Anaesthesia. 2020 Oct;75(10):1340-1349
pubmed: 32602561
Lancet. 2020 Jun 6;395(10239):1763-1770
pubmed: 32442528
JAMA Intern Med. 2021 Jan 1;181(1):140-141
pubmed: 32744600
Toxicol Appl Pharmacol. 2019 Oct 1;380:114698
pubmed: 31394157
EClinicalMedicine. 2020 Aug;25:100449
pubmed: 32838231
JAMA Intern Med. 2021 Jan 1;181(1):140
pubmed: 32744591
J Leukoc Biol. 2020 Jul;108(1):17-41
pubmed: 32534467
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
J Allergy Clin Immunol. 2020 Jul;146(1):119-127.e4
pubmed: 32360286
PLoS One. 2015 Mar 18;10(3):e0120012
pubmed: 25785720
Am J Respir Crit Care Med. 2020 Dec 1;202(11):1509-1519
pubmed: 32866033
Lancet Respir Med. 2020 Dec;8(12):1170-1172
pubmed: 33129421
Cleve Clin J Med. 2020 Oct 7;:
pubmed: 32409439
Eur J Clin Microbiol Infect Dis. 2018 Jul;37(7):1361-1371
pubmed: 29700762
J Infect. 2020 Jun;80(6):607-613
pubmed: 32283152
Crit Care. 2020 Aug 5;24(1):486
pubmed: 32758266
Autoimmun Rev. 2020 Jun;19(6):102537
pubmed: 32251717
Crit Care. 2020 Jul 18;24(1):445
pubmed: 32682440
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
PLoS One. 2013 Dec 12;8(12):e82204
pubmed: 24349222
N Engl J Med. 2020 Jul 17;:
pubmed: 32678530
Am J Respir Crit Care Med. 2020 Sep 15;202(6):812-821
pubmed: 32584597
Nat Rev Immunol. 2020 Jun;20(6):363-374
pubmed: 32346093
J Infect Dis. 2020 Aug 4;222(5):746-754
pubmed: 32563194