Decreased plasma H<sub>2</sub>O<sub>2</sub> levels are associated with the pathogenesis leading to COVID-19 worsening and mortality

Cavalcanti, Liara Freitas; Silva, Isabela Chagas; Nascimento, Thiago Henrique Daniel do; Melo, Jôse de; Grion, Cíntia Magalhães Carvalho; Cecchini, Alessandra Lourenço; Cecchini, Rúbens

doi:10.1080/10715762.2023.2174021

Cited by 3 publications

(2 citation statements)

References 46 publications

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“…Serum levels of SOD, CAT, GSH, and GPx are significantly altered in COVID-19 patients 560 , 561 . The depleted total antioxidant capacity (in blood) of SARS-CoV-2 infected individuals serves as a predictive marker for COVID-19 severity 562 .…”

Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 96%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

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SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

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Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 96%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

View full text Add to dashboard Cite

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“…As a result of albumin oxidation, the formation of dimeric disulfides is not excluded [ 54 ] during the generation of sulfenic acid as an intermediate in redox modulation. Cavalcanti et al [ 55 ] note the role of OS in the pathogenesis of COVID-19. They unravel the role of H 2 O 2 in critically ill COVID-19 patients and its conversion to highly reactive ROS.…”

Section: Discussionmentioning

confidence: 99%

Direct Application of 3-Maleimido-PROXYL for Proving Hypoalbuminemia in Cases of SARS-CoV-2 Infection: The Potential Diagnostic Method of Determining Albumin Instability and Oxidized Protein Level in Severe COVID-19

Georgieva

Atanasov

Kostandieva

et al. 2023

IJMS

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Oxidative stress and the albumin oxidized form can lead to hypoalbuminemia, which is a predisposing factor for reduced treatment effectiveness and an increased mortality rate in severe COVID-19 patients. The aim of the study is to evaluate the application of free radical 3-Maleimido-PROXYL and SDSL-EPR spectroscopy in the in vitro determination of ox/red HSA in serum samples from patients with SARS-CoV-2 infection. Venous blood was collected from patients intubated (pO2 < 90%) with a positive PCR test for SARS-CoV-2 and controls. At the 120th minute after the incubation of the serum samples from both groups with the 3-Maleimido-PROXYL, the EPR measurement was started. The high levels of free radicals were determined through the nitroxide radical TEMPOL, which probably led to increased oxidation of HSA and hypoalbuminemia in severe COVID-19. The double-integrated spectra of 3-Maleimido-PROXYL radical showed a low degree of connectivity due to high levels of oxidized albumin in COVID-19 patients. The low concentrations of reduced albumin in serum samples partially inhibit spin-label rotation, with Amax values and ΔH0 spectral parameters comparable to those of 3-Maleimido-PROXYL/DMSO. Based on the obtained results, we suggest that the stable nitroxide radical 3-Maleimido-PROXYL can be successfully used as a marker to study oxidized albumin levels in COVID-19.

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Stable Nitroxide as Diagnostic Tools for Monitoring of Oxidative Stress and Hypoalbuminemia in the Context of COVID-19

Georgieva,

Ananiev,

Yovchev

et al. 2024

IJMS

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Oxidative stress is a major source of ROS-mediated damage to macromolecules, tissues, and the whole body. It is an important marker in the severe picture of pathological conditions. The discovery of free radicals in biological systems gives a “start” to studying various pathological processes related to the development and progression of many diseases. From this moment on, the enrichment of knowledge about the participation of free radicals and free-radical processes in the pathogenesis of cardiovascular, neurodegenerative, and endocrine diseases, inflammatory conditions, and infections, including COVID-19, is increasing exponentially. Excessive inflammatory responses and abnormal reactive oxygen species (ROS) levels may disrupt mitochondrial dynamics, increasing the risk of cell damage. In addition, low serum albumin levels and changes in the normal physiological balance between reduced and oxidized albumin can be a serious prerequisite for impaired antioxidant capacity of the body, worsening the condition in patients. This review presents the interrelationship between oxidative stress, inflammation, and low albumin levels, which are hallmarks of COVID-19.

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Decreased plasma H₂O₂ levels are associated with the pathogenesis leading to COVID-19 worsening and mortality

Cited by 3 publications

References 46 publications

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Direct Application of 3-Maleimido-PROXYL for Proving Hypoalbuminemia in Cases of SARS-CoV-2 Infection: The Potential Diagnostic Method of Determining Albumin Instability and Oxidized Protein Level in Severe COVID-19

Stable Nitroxide as Diagnostic Tools for Monitoring of Oxidative Stress and Hypoalbuminemia in the Context of COVID-19

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Decreased plasma H2O2 levels are associated with the pathogenesis leading to COVID-19 worsening and mortality

Cited by 3 publications

References 46 publications

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Direct Application of 3-Maleimido-PROXYL for Proving Hypoalbuminemia in Cases of SARS-CoV-2 Infection: The Potential Diagnostic Method of Determining Albumin Instability and Oxidized Protein Level in Severe COVID-19

Stable Nitroxide as Diagnostic Tools for Monitoring of Oxidative Stress and Hypoalbuminemia in the Context of COVID-19

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Decreased plasma H₂O₂ levels are associated with the pathogenesis leading to COVID-19 worsening and mortality