COVID-19 - a redox disease what a stress pandemic can teach us about resilience and what we may learn from the reactive species interactome about its treatment
COVID-19 - a redox disease what a stress pandemic can teach us about resilience and what we may learn from the reactive species interactome about its treatment
Significance:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), affects every aspect of human life by challenging bodily, socioeconomic, and political systems at unprecedented levels. As vaccines become available, their distribution, safety, and efficacy against emerging variants remain uncertain, and specific treatments are lacking.
Recent Advances:
Initially affecting the lungs, COVID-19 is a complex multisystems disease that disturbs the whole-body redox balance and can be long-lasting (Long-COVID). Numerous risk factors have been identified, but the reasons for variations in susceptibility to infection, disease severity, and outcome are poorly understood. The reactive species interactome (RSI) was recently introduced as a framework to conceptualize how cells and whole organisms sense, integrate, and accommodate stress.
Critical Issues:
We here consider COVID-19 as a redox disease, offering a holistic perspective of its effects on the human body, considering the vulnerability of complex interconnected systems with multiorgan/multilevel interdependencies. Host/viral glycan interactions underpin SARS-CoV-2's extraordinary efficiency in gaining cellular access, crossing the epithelial/endothelial barrier to spread along the vascular/lymphatic endothelium, and evading antiviral/antioxidant defences. An inflammation-driven "oxidative storm" alters the redox landscape, eliciting epithelial, endothelial, mitochondrial, metabolic, and immune dysfunction, and coagulopathy. Concomitantly reduced nitric oxide availability renders the sulfur-based redox circuitry vulnerable to oxidation, with eventual catastrophic failure in redox communication/regulation. Host nutrient limitations are crucial determinants of resilience at the individual and population level.
Future Directions:
While inflicting considerable damage to health and well-being, COVID-19 may provide the ultimate testing ground to improve the diagnosis and treatment of redox-related stress diseases. "Redox phenotyping" of patients to characterize whole-body RSI status as the disease progresses may inform new therapeutic approaches to regain redox balance, reduce mortality in COVID-19 and other redox diseases, and provide opportunities to tackle Long-COVID.
coronavirus, endothelium, glycobiology, nutrition, oxidative stress, redox regulation
1226-1268
Cumpstey, Andrew F
050a389c-f550-4453-a80a-f1a6e57db923
Clark, Anna D
aa64a0c0-e039-4e73-b3bf-a71dcbf7a729
Santolini, Jerome
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Jackson, Alan A
c9a12d7c-b4d6-4c92-820e-890a688379ef
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
13 May 2021
Cumpstey, Andrew F
050a389c-f550-4453-a80a-f1a6e57db923
Clark, Anna D
aa64a0c0-e039-4e73-b3bf-a71dcbf7a729
Santolini, Jerome
2e9403c4-40a3-4e49-bd50-916d01de14da
Jackson, Alan A
c9a12d7c-b4d6-4c92-820e-890a688379ef
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Cumpstey, Andrew F, Clark, Anna D, Santolini, Jerome, Jackson, Alan A and Feelisch, Martin
(2021)
COVID-19 - a redox disease what a stress pandemic can teach us about resilience and what we may learn from the reactive species interactome about its treatment.
Antioxidants & Redox Signaling, 35 (14), .
(doi:10.1089/ars.2021.0017).
Abstract
Significance:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), affects every aspect of human life by challenging bodily, socioeconomic, and political systems at unprecedented levels. As vaccines become available, their distribution, safety, and efficacy against emerging variants remain uncertain, and specific treatments are lacking.
Recent Advances:
Initially affecting the lungs, COVID-19 is a complex multisystems disease that disturbs the whole-body redox balance and can be long-lasting (Long-COVID). Numerous risk factors have been identified, but the reasons for variations in susceptibility to infection, disease severity, and outcome are poorly understood. The reactive species interactome (RSI) was recently introduced as a framework to conceptualize how cells and whole organisms sense, integrate, and accommodate stress.
Critical Issues:
We here consider COVID-19 as a redox disease, offering a holistic perspective of its effects on the human body, considering the vulnerability of complex interconnected systems with multiorgan/multilevel interdependencies. Host/viral glycan interactions underpin SARS-CoV-2's extraordinary efficiency in gaining cellular access, crossing the epithelial/endothelial barrier to spread along the vascular/lymphatic endothelium, and evading antiviral/antioxidant defences. An inflammation-driven "oxidative storm" alters the redox landscape, eliciting epithelial, endothelial, mitochondrial, metabolic, and immune dysfunction, and coagulopathy. Concomitantly reduced nitric oxide availability renders the sulfur-based redox circuitry vulnerable to oxidation, with eventual catastrophic failure in redox communication/regulation. Host nutrient limitations are crucial determinants of resilience at the individual and population level.
Future Directions:
While inflicting considerable damage to health and well-being, COVID-19 may provide the ultimate testing ground to improve the diagnosis and treatment of redox-related stress diseases. "Redox phenotyping" of patients to characterize whole-body RSI status as the disease progresses may inform new therapeutic approaches to regain redox balance, reduce mortality in COVID-19 and other redox diseases, and provide opportunities to tackle Long-COVID.
Text
ars.2021.0017
- Accepted Manuscript
More information
e-pub ahead of print date: 13 May 2021
Published date: 13 May 2021
Additional Information:
Funding Information:
The authors are indebted to their families for their support and stimulating discussions with friends and colleagues during one of the most challenging times of their lifetime. M.F. is grateful for previous research support, which helped shape his thinking, from the U.S. National Institutes of Health, the UK Medical Research Council, and the Wellcome Trust and current funding from The Bill & Melinda Gates Foundation (INV-016631).
Funding Information:
A.D.C. has received funding through the NIHR Academic Foundation Programme. A.F.C. is funded by the National Institute for Health Research Southampton Biomedical Research Centre. No specific funding was received for preparation of this article.
Publisher Copyright:
© Andrew F. Cumpstey et al., 2021; Published by Mary Ann Liebert, Inc. 2021.
Keywords:
coronavirus, endothelium, glycobiology, nutrition, oxidative stress, redox regulation
Identifiers
Local EPrints ID: 449576
URI: http://eprints.soton.ac.uk/id/eprint/449576
ISSN: 1523-0864
PURE UUID: 12af329d-ef49-4785-bf47-0641de8f328a
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Date deposited: 08 Jun 2021 16:31
Last modified: 12 Apr 2024 04:04
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Author:
Andrew F Cumpstey
Author:
Anna D Clark
Author:
Jerome Santolini
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