Oxidative stress-induced endothelial dysfunction and decreased vascular nitric oxide in COVID-19 patients.

Adult COVID-19 Endothelial Cells Humans Nitric Oxide Oxidative Stress SARS-CoV-2

Angiotensin II Endothelial dysfunction Microvascular thrombosis Nitric oxide Oxidative stress SARS-CoV-2

Journal

EBioMedicine

ISSN: 2352-3964

Titre abrégé: EBioMedicine

Pays: Netherlands

ID NLM: 101647039

Informations de publication

Date de publication:
Mar 2022

Historique:

received: 10 09 2021

revised: 10 01 2022

accepted: 08 02 2022

pubmed: 27 2 2022

medline: 1 4 2022

entrez: 26 2 2022

Statut: ppublish

Résumé

SARS-CoV-2 targets endothelial cells through the angiotensin-converting enzyme 2 receptor. The resulting endothelial injury induces widespread thrombosis and microangiopathy. Nevertheless, early specific markers of endothelial dysfunction and vascular redox status in COVID-19 patients are currently missing. Observational study including ICU and non-ICU adult COVID-19 patients admitted in hospital for acute respiratory failure, compared with control subjects matched for cardiovascular risk factors similar to ICU COVID-19 patients, and ICU septic shock patients unrelated to COVID-19. Early SARS-CoV-2 infection was associated with an imbalance between an exacerbated oxidative stress (plasma peroxides levels in ICU patients vs. controls: 1456.0 ± 400.2 vs 436 ± 272.1 mmol/L; P < 0.05) and a reduced nitric oxide bioavailability proportional to disease severity (5-α-nitrosyl-hemoglobin, HbNO in ICU patients vs. controls: 116.1 ± 62.1 vs. 163.3 ± 46.7 nmol/L; P < 0.05). HbNO levels correlated with oxygenation parameters (PaO Endothelial oxidative stress with ensuing decreased NO bioavailability appears as a likely pathogenic factor of endothelial dysfunction in ICU COVID-19 patients. A correlation between NO bioavailability and oxygenation parameters is observed in hospitalized COVID-19 patients. These results highlight an urgent need for oriented research leading to a better understanding of the specific endothelial oxidative stress that occurs during SARS-CoV-2. Stated in the acknowledgments section.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

Observational study including ICU and non-ICU adult COVID-19 patients admitted in hospital for acute respiratory failure, compared with control subjects matched for cardiovascular risk factors similar to ICU COVID-19 patients, and ICU septic shock patients unrelated to COVID-19.

FINDINGS RESULTS

Early SARS-CoV-2 infection was associated with an imbalance between an exacerbated oxidative stress (plasma peroxides levels in ICU patients vs. controls: 1456.0 ± 400.2 vs 436 ± 272.1 mmol/L; P < 0.05) and a reduced nitric oxide bioavailability proportional to disease severity (5-α-nitrosyl-hemoglobin, HbNO in ICU patients vs. controls: 116.1 ± 62.1 vs. 163.3 ± 46.7 nmol/L; P < 0.05). HbNO levels correlated with oxygenation parameters (PaO

INTERPRETATION CONCLUSIONS

Endothelial oxidative stress with ensuing decreased NO bioavailability appears as a likely pathogenic factor of endothelial dysfunction in ICU COVID-19 patients. A correlation between NO bioavailability and oxygenation parameters is observed in hospitalized COVID-19 patients. These results highlight an urgent need for oriented research leading to a better understanding of the specific endothelial oxidative stress that occurs during SARS-CoV-2.

FUNDING BACKGROUND

Stated in the acknowledgments section.

Identifiants

DOI: 10.1016/j.ebiom.2022.103893 PMID: 35219085 PMC: PMC8865837

pubmed: 35219085

pii: S2352-3964(22)00077-9

doi: 10.1016/j.ebiom.2022.103893

pmc: PMC8865837

pii:

doi:

Substances chimiques

Nitric Oxide 31C4KY9ESH

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

Pagination

103893

Commentaires et corrections

Type : CommentIn

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests Marc Derive is a co-founder and employee of Inotrem Company, a drug development company that is developing anti-TREM-1 approaches in septic shock and COVID-19. The other authors have disclosed that they do not have any potential conflicts of interest.