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RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19

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Wick, KD, Siegel, L, Neaton, JD, Oldmixon, C, Lundgren, J, Dewar, RL, Lane, HC, Thompson, BT & Matthay, MA 2022, 'RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19', JCI Insight, bind 7, nr. 9, e157499. https://doi.org/10.1172/jci.insight.157499

APA

Wick, K. D., Siegel, L., Neaton, J. D., Oldmixon, C., Lundgren, J., Dewar, R. L., Lane, H. C., Thompson, B. T., & Matthay, M. A. (2022). RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19. JCI Insight, 7(9), [e157499]. https://doi.org/10.1172/jci.insight.157499

CBE

Wick KD, Siegel L, Neaton JD, Oldmixon C, Lundgren J, Dewar RL, Lane HC, Thompson BT, Matthay MA. 2022. RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19. JCI Insight. 7(9):Article e157499. https://doi.org/10.1172/jci.insight.157499

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Author

Wick, Katherine D ; Siegel, Lianne ; Neaton, James D ; Oldmixon, Cathryn ; Lundgren, Jens ; Dewar, Robin L ; Lane, H Clifford ; Thompson, B Taylor ; Matthay, Michael A. / RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19. I: JCI Insight. 2022 ; Bind 7, Nr. 9.

Bibtex

@article{6378af4926ca42f5a61180bf1e858e69,
title = "RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19",
abstract = "BackgroundThe value of the soluble receptor for advanced glycation end-products (sRAGE) as a biomarker in COVID-19 is not well understood. We tested the association between plasma sRAGE and illness severity, viral burden, and clinical outcomes in hospitalized patients with COVID-19 who were not mechanically ventilated.MethodsBaseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of bamlanivimab for hospitalized patients with COVID-19. Spearman's rank correlation was used to assess the relationship between sRAGE and other plasma biomarkers, including viral nucleocapsid antigen. Fine-Gray models adjusted for baseline supplemental oxygen requirement, antigen level, positive endogenous anti-nucleocapsid antibody response, sex, age, BMI, diabetes mellitus, renal impairment, corticosteroid treatment, and log2-transformed IL-6 level were used to assess the association between baseline sRAGE and time to sustained recovery. Cox regression adjusted for the same factors was used to assess the association between sRAGE and mortality.ResultsAmong 277 participants, baseline sRAGE was strongly correlated with viral plasma antigen concentration (ρ = 0.57). There was a weaker correlation between sRAGE and biomarkers of systemic inflammation, such as IL-6 (ρ = 0.36) and CRP (ρ = 0.20). Participants with plasma sRAGE in the highest quartile had a significantly lower rate of sustained recovery (adjusted recovery rate ratio, 0.64 [95% CI, 0.43-0.90]) and a higher unadjusted risk of death (HR, 4.70 [95% CI, 2.01-10.99]) compared with participants in the lower quartiles.ConclusionElevated plasma sRAGE in hospitalized, nonventilated patients with COVID-19 was an indicator of both clinical illness severity and plasma viral load. Plasma sRAGE in the highest quartile was associated with a lower likelihood of sustained recovery and higher unadjusted risk of death. These findings, which we believe to be novel, indicate that plasma sRAGE may be a promising biomarker for COVID-19 prognostication and clinical trial enrichment.Trial RegistrationClinicalTrials.gov NCT04501978.FundingNIH (5T32GM008440-24, 18X107CF6, HHSN261201500003I, R35HL140026, and OT2HL156812).",
keywords = "Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, Biomarkers, COVID-19, Humans, Interleukin-6, Prognosis, Receptor for Advanced Glycation End Products",
author = "Wick, {Katherine D} and Lianne Siegel and Neaton, {James D} and Cathryn Oldmixon and Jens Lundgren and Dewar, {Robin L} and Lane, {H Clifford} and Thompson, {B Taylor} and Matthay, {Michael A}",
year = "2022",
month = may,
day = "9",
doi = "10.1172/jci.insight.157499",
language = "English",
volume = "7",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "9",

}

RIS

TY - JOUR

T1 - RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19

AU - Wick, Katherine D

AU - Siegel, Lianne

AU - Neaton, James D

AU - Oldmixon, Cathryn

AU - Lundgren, Jens

AU - Dewar, Robin L

AU - Lane, H Clifford

AU - Thompson, B Taylor

AU - Matthay, Michael A

PY - 2022/5/9

Y1 - 2022/5/9

N2 - BackgroundThe value of the soluble receptor for advanced glycation end-products (sRAGE) as a biomarker in COVID-19 is not well understood. We tested the association between plasma sRAGE and illness severity, viral burden, and clinical outcomes in hospitalized patients with COVID-19 who were not mechanically ventilated.MethodsBaseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of bamlanivimab for hospitalized patients with COVID-19. Spearman's rank correlation was used to assess the relationship between sRAGE and other plasma biomarkers, including viral nucleocapsid antigen. Fine-Gray models adjusted for baseline supplemental oxygen requirement, antigen level, positive endogenous anti-nucleocapsid antibody response, sex, age, BMI, diabetes mellitus, renal impairment, corticosteroid treatment, and log2-transformed IL-6 level were used to assess the association between baseline sRAGE and time to sustained recovery. Cox regression adjusted for the same factors was used to assess the association between sRAGE and mortality.ResultsAmong 277 participants, baseline sRAGE was strongly correlated with viral plasma antigen concentration (ρ = 0.57). There was a weaker correlation between sRAGE and biomarkers of systemic inflammation, such as IL-6 (ρ = 0.36) and CRP (ρ = 0.20). Participants with plasma sRAGE in the highest quartile had a significantly lower rate of sustained recovery (adjusted recovery rate ratio, 0.64 [95% CI, 0.43-0.90]) and a higher unadjusted risk of death (HR, 4.70 [95% CI, 2.01-10.99]) compared with participants in the lower quartiles.ConclusionElevated plasma sRAGE in hospitalized, nonventilated patients with COVID-19 was an indicator of both clinical illness severity and plasma viral load. Plasma sRAGE in the highest quartile was associated with a lower likelihood of sustained recovery and higher unadjusted risk of death. These findings, which we believe to be novel, indicate that plasma sRAGE may be a promising biomarker for COVID-19 prognostication and clinical trial enrichment.Trial RegistrationClinicalTrials.gov NCT04501978.FundingNIH (5T32GM008440-24, 18X107CF6, HHSN261201500003I, R35HL140026, and OT2HL156812).

AB - BackgroundThe value of the soluble receptor for advanced glycation end-products (sRAGE) as a biomarker in COVID-19 is not well understood. We tested the association between plasma sRAGE and illness severity, viral burden, and clinical outcomes in hospitalized patients with COVID-19 who were not mechanically ventilated.MethodsBaseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of bamlanivimab for hospitalized patients with COVID-19. Spearman's rank correlation was used to assess the relationship between sRAGE and other plasma biomarkers, including viral nucleocapsid antigen. Fine-Gray models adjusted for baseline supplemental oxygen requirement, antigen level, positive endogenous anti-nucleocapsid antibody response, sex, age, BMI, diabetes mellitus, renal impairment, corticosteroid treatment, and log2-transformed IL-6 level were used to assess the association between baseline sRAGE and time to sustained recovery. Cox regression adjusted for the same factors was used to assess the association between sRAGE and mortality.ResultsAmong 277 participants, baseline sRAGE was strongly correlated with viral plasma antigen concentration (ρ = 0.57). There was a weaker correlation between sRAGE and biomarkers of systemic inflammation, such as IL-6 (ρ = 0.36) and CRP (ρ = 0.20). Participants with plasma sRAGE in the highest quartile had a significantly lower rate of sustained recovery (adjusted recovery rate ratio, 0.64 [95% CI, 0.43-0.90]) and a higher unadjusted risk of death (HR, 4.70 [95% CI, 2.01-10.99]) compared with participants in the lower quartiles.ConclusionElevated plasma sRAGE in hospitalized, nonventilated patients with COVID-19 was an indicator of both clinical illness severity and plasma viral load. Plasma sRAGE in the highest quartile was associated with a lower likelihood of sustained recovery and higher unadjusted risk of death. These findings, which we believe to be novel, indicate that plasma sRAGE may be a promising biomarker for COVID-19 prognostication and clinical trial enrichment.Trial RegistrationClinicalTrials.gov NCT04501978.FundingNIH (5T32GM008440-24, 18X107CF6, HHSN261201500003I, R35HL140026, and OT2HL156812).

KW - Antibodies, Monoclonal, Humanized

KW - Antibodies, Neutralizing

KW - Biomarkers

KW - COVID-19

KW - Humans

KW - Interleukin-6

KW - Prognosis

KW - Receptor for Advanced Glycation End Products

UR - http://www.scopus.com/inward/record.url?scp=85129971354&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.157499

DO - 10.1172/jci.insight.157499

M3 - Journal article

C2 - 35298440

VL - 7

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 9

M1 - e157499

ER -

ID: 75683339