Association between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia and Clotting Activation in COVID-19

Roberto Carnevale; Cristina Nocella; Raffaella Marocco; Paola Zuccalà; Anna Carraro; Vittorio Picchio; Alessandra Oliva; Roberto Cangemi; Maria Claudia Miele; Massimiliano De Angelis; Francesca Cancelli; Giovanni Enrico Casciaro; Luca Cristiano; Pasquale Pignatelli; Giacomo Frati; Mario Venditti; Francesco Pugliese; Claudio Maria Mastroianni; Francesco Violi; Lorenzo Ridola; Cosmo Del Borgo; Silvia Palmerio; Emiliano Valenzi; Rita Carnevale; Domenico Alvaro; Miriam Lichtner; Vincenzo Cardinale

doi:10.20944/preprints202409.2141.v1

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preprints.org > biology and life sciences > life sciences > doi: 10.20944/preprints202409.2141.v1

Preprint Article Version 1 This version is not peer-reviewed

Association between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia and Clotting Activation in COVID-19

^* ,

Massimiliano De Angelis

Francesca Cancelli

Giovanni Enrico Casciaro

Claudio Maria Mastroianni

Version 1 : Received: 26 September 2024 / Approved: 26 September 2024 / Online: 26 September 2024 (16:39:01 CEST)

How to cite: Carnevale, R.; Nocella, C.; Marocco, R.; Zuccalà, P.; Carraro, A.; Picchio, V.; Oliva, A.; Cangemi, R.; Miele, M. C.; De Angelis, M.; Cancelli, F.; Casciaro, G. E.; Cristiano, L.; Pignatelli, P.; Frati, G.; Venditti, M.; Pugliese, F.; Mastroianni, C. M.; Violi, F.; Ridola, L.; Del Borgo, C.; Palmerio, S.; Valenzi, E.; Carnevale, R.; Alvaro, D.; Lichtner, M.; Cardinale, V. Association between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia and Clotting Activation in COVID-19. Preprints 2024, 2024092141. https://doi.org/10.20944/preprints202409.2141.v1 Carnevale, R.; Nocella, C.; Marocco, R.; Zuccalà, P.; Carraro, A.; Picchio, V.; Oliva, A.; Cangemi, R.; Miele, M. C.; De Angelis, M.; Cancelli, F.; Casciaro, G. E.; Cristiano, L.; Pignatelli, P.; Frati, G.; Venditti, M.; Pugliese, F.; Mastroianni, C. M.; Violi, F.; Ridola, L.; Del Borgo, C.; Palmerio, S.; Valenzi, E.; Carnevale, R.; Alvaro, D.; Lichtner, M.; Cardinale, V. Association between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia and Clotting Activation in COVID-19. Preprints 2024, 2024092141. https://doi.org/10.20944/preprints202409.2141.v1

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MDPI and ACS Style

Carnevale, R.; Nocella, C.; Marocco, R.; Zuccalà, P.; Carraro, A.; Picchio, V.; Oliva, A.; Cangemi, R.; Miele, M. C.; De Angelis, M.; Cancelli, F.; Casciaro, G. E.; Cristiano, L.; Pignatelli, P.; Frati, G.; Venditti, M.; Pugliese, F.; Mastroianni, C. M.; Violi, F.; Ridola, L.; Del Borgo, C.; Palmerio, S.; Valenzi, E.; Carnevale, R.; Alvaro, D.; Lichtner, M.; Cardinale, V. Association between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia and Clotting Activation in COVID-19. Preprints 2024, 2024092141. https://doi.org/10.20944/preprints202409.2141.v1

APA Style

Carnevale, R., Nocella, C., Marocco, R., Zuccalà, P., Carraro, A., Picchio, V., Oliva, A., Cangemi, R., Miele, M. C., De Angelis, M., Cancelli, F., Casciaro, G. E., Cristiano, L., Pignatelli, P., Frati, G., Venditti, M., Pugliese, F., Mastroianni, C. M., Violi, F., Ridola, L., Del Borgo, C., Palmerio, S., Valenzi, E., Carnevale, R., Alvaro, D., Lichtner, M., & Cardinale, V. (2024). Association between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia and Clotting Activation in COVID-19. Preprints. https://doi.org/10.20944/preprints202409.2141.v1

Chicago/Turabian Style

Carnevale, R., Miriam Lichtner and Vincenzo Cardinale. 2024 "Association between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia and Clotting Activation in COVID-19" Preprints. https://doi.org/10.20944/preprints202409.2141.v1

Abstract

Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favour thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of the study was to analyse the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with compared with those without ARDS and inversely associated with LPS. In COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp, and LPS and D-Dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/Albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers, that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation and low serum albumin may account for low-grade endotoxemia, and they may be implicated in thrombotic events in COVID-19.

Keywords

oxidative stress; NOX2 activation; albumin; D-dimer; gut permeability; low-grade endotoxemia; thrombosis

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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