High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis

Abstract The severe acute respiratory syndrome coronavirus 2, the agent of the ongoing coronavirus disease 2019 (COVID‐19) pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan, China. Since then, progress in pathogenesis linked severity of this systemic disease to t...

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Main Authors: Amanda Roberta Revoredo Vicentino, Vanderlei da Silva Fraga‐Junior, Matheus Palazzo, Natalia Recardo Amorim Tasmo, Danielle A. S. Rodrigues, Shana Priscila Coutinho Barroso, Sâmila Natiane Ferreira, Anna Cristina Neves‐Borges, Diego Allonso, Marcelo Rosado Fantappié, Julio Scharfstein, Ana Carolina Oliveira, Rosane Vianna‐Jorge, André Macedo Vale, Robson Coutinho‐Silva, Luiz Eduardo Baggio Savio, Claudio Canetti, Claudia Farias Benjamim
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:Clinical and Translational Science
Online Access:https://doi.org/10.1111/cts.13475
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author Amanda Roberta Revoredo Vicentino
Vanderlei da Silva Fraga‐Junior
Matheus Palazzo
Natalia Recardo Amorim Tasmo
Danielle A. S. Rodrigues
Shana Priscila Coutinho Barroso
Sâmila Natiane Ferreira
Anna Cristina Neves‐Borges
Diego Allonso
Marcelo Rosado Fantappié
Julio Scharfstein
Ana Carolina Oliveira
Rosane Vianna‐Jorge
André Macedo Vale
Robson Coutinho‐Silva
Luiz Eduardo Baggio Savio
Claudio Canetti
Claudia Farias Benjamim
author_facet Amanda Roberta Revoredo Vicentino
Vanderlei da Silva Fraga‐Junior
Matheus Palazzo
Natalia Recardo Amorim Tasmo
Danielle A. S. Rodrigues
Shana Priscila Coutinho Barroso
Sâmila Natiane Ferreira
Anna Cristina Neves‐Borges
Diego Allonso
Marcelo Rosado Fantappié
Julio Scharfstein
Ana Carolina Oliveira
Rosane Vianna‐Jorge
André Macedo Vale
Robson Coutinho‐Silva
Luiz Eduardo Baggio Savio
Claudio Canetti
Claudia Farias Benjamim
author_sort Amanda Roberta Revoredo Vicentino
collection DOAJ
description Abstract The severe acute respiratory syndrome coronavirus 2, the agent of the ongoing coronavirus disease 2019 (COVID‐19) pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan, China. Since then, progress in pathogenesis linked severity of this systemic disease to the hyperactivation of network of cytokine‐driven pro‐inflammatory cascades. Here, we aimed to identify molecular biomarkers of disease severity by measuring the serum levels of inflammatory mediators in a Brazilian cohort of patients with COVID‐19 and healthy controls (HCs). Critically ill patients in the intensive care unit were defined as such by dependence on oxygen supplementation (93% intubated and 7% face mask), and computed tomography profiles showing ground‐glass opacity pneumonia associated to and high levels of D‐dimer. Our panel of mediators included HMGB1, ATP, tissue factor, PGE2, LTB4, and cys‐LTs. Follow‐up studies showed increased serum levels of every inflammatory mediator in patients with COVID‐19 as compared to HCs. Originally acting as a transcription factor, HMGB1 acquires pro‐inflammatory functions following secretion by activated leukocytes or necrotic tissues. Serum levels of HMGB1 were positively correlated with cys‐LTs, D‐dimer, aspartate aminotransferase, and alanine aminotransferase. Notably, the levels of the classical alarmin HMGB1 were higher in deceased patients, allowing their discrimination from patients that had been discharged at the early pulmonary and hyperinflammatory phase of COVID‐19. In particular, we verified that HMGB1 levels above 125.4 ng/ml is the cutoff that distinguishes patients that are at higher risk of death. In conclusion, we propose the use of serum levels of HMGB1 as a biomarker of severe prognosis of COVID‐19.
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spelling doaj.art-0d44ed7490b24374acc447aaa243ed8c2023-04-11T09:22:04ZengWileyClinical and Translational Science1752-80541752-80622023-04-0116463164610.1111/cts.13475High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosisAmanda Roberta Revoredo Vicentino0Vanderlei da Silva Fraga‐Junior1Matheus Palazzo2Natalia Recardo Amorim Tasmo3Danielle A. S. Rodrigues4Shana Priscila Coutinho Barroso5Sâmila Natiane Ferreira6Anna Cristina Neves‐Borges7Diego Allonso8Marcelo Rosado Fantappié9Julio Scharfstein10Ana Carolina Oliveira11Rosane Vianna‐Jorge12André Macedo Vale13Robson Coutinho‐Silva14Luiz Eduardo Baggio Savio15Claudio Canetti16Claudia Farias Benjamim17Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilMolecular Biology Laboratory Laboratório de Biologia Molecular, Instituto de Pesquisas Biomédicas, Hospital Naval Marcílio Dias Rio de Janeiro BrazilMolecular Biology Laboratory Laboratório de Biologia Molecular, Instituto de Pesquisas Biomédicas, Hospital Naval Marcílio Dias Rio de Janeiro BrazilDepartment of Botanic Departamento de Botânica, Instituto de Biociências, Universidade Federal do Estado do Rio de Janeiro Rio de Janeiro BrazilDepartamento de Biotecnologia Farmacêutica, Faculdade de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Biologia Molecular e Biotecnologia, Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilPrograma de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro Rio de Janeiro BrazilAbstract The severe acute respiratory syndrome coronavirus 2, the agent of the ongoing coronavirus disease 2019 (COVID‐19) pandemic, has spread worldwide since it was first identified in November 2019 in Wuhan, China. Since then, progress in pathogenesis linked severity of this systemic disease to the hyperactivation of network of cytokine‐driven pro‐inflammatory cascades. Here, we aimed to identify molecular biomarkers of disease severity by measuring the serum levels of inflammatory mediators in a Brazilian cohort of patients with COVID‐19 and healthy controls (HCs). Critically ill patients in the intensive care unit were defined as such by dependence on oxygen supplementation (93% intubated and 7% face mask), and computed tomography profiles showing ground‐glass opacity pneumonia associated to and high levels of D‐dimer. Our panel of mediators included HMGB1, ATP, tissue factor, PGE2, LTB4, and cys‐LTs. Follow‐up studies showed increased serum levels of every inflammatory mediator in patients with COVID‐19 as compared to HCs. Originally acting as a transcription factor, HMGB1 acquires pro‐inflammatory functions following secretion by activated leukocytes or necrotic tissues. Serum levels of HMGB1 were positively correlated with cys‐LTs, D‐dimer, aspartate aminotransferase, and alanine aminotransferase. Notably, the levels of the classical alarmin HMGB1 were higher in deceased patients, allowing their discrimination from patients that had been discharged at the early pulmonary and hyperinflammatory phase of COVID‐19. In particular, we verified that HMGB1 levels above 125.4 ng/ml is the cutoff that distinguishes patients that are at higher risk of death. In conclusion, we propose the use of serum levels of HMGB1 as a biomarker of severe prognosis of COVID‐19.https://doi.org/10.1111/cts.13475
spellingShingle Amanda Roberta Revoredo Vicentino
Vanderlei da Silva Fraga‐Junior
Matheus Palazzo
Natalia Recardo Amorim Tasmo
Danielle A. S. Rodrigues
Shana Priscila Coutinho Barroso
Sâmila Natiane Ferreira
Anna Cristina Neves‐Borges
Diego Allonso
Marcelo Rosado Fantappié
Julio Scharfstein
Ana Carolina Oliveira
Rosane Vianna‐Jorge
André Macedo Vale
Robson Coutinho‐Silva
Luiz Eduardo Baggio Savio
Claudio Canetti
Claudia Farias Benjamim
High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis
Clinical and Translational Science
title High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis
title_full High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis
title_fullStr High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis
title_full_unstemmed High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis
title_short High mobility group box 1, ATP, lipid mediators, and tissue factor are elevated in COVID‐19 patients: HMGB1 as a biomarker of worst prognosis
title_sort high mobility group box 1 atp lipid mediators and tissue factor are elevated in covid 19 patients hmgb1 as a biomarker of worst prognosis
url https://doi.org/10.1111/cts.13475
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