ReviewAgeing research reviews2020
Does eNOS derived nitric oxide protect the young from severe COVID-19 complications?
Review in Ageing research reviews, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 52 citations in OpenAlex.
- Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial.Critical care (London, England) · 2022Trial
- Impact of Nitric Oxide Metabolites On Early Perioperative Biochemical Changes and Postoperative Complications in High-BMI Patients Undergoing On-Pump CABG: an Exploratory Observational Cohort Study.Cardiovascular drugs and therapy · 2026Article
- Association of Endothelial Nitric Oxide Synthase Polymorphisms with Clinical Severity in Patients with COVID-19.Journal of clinical medicine · 2025Article
- The role of NOS3-rs1799983 and NOS3- rs2070744 SNP in occurrence of avascular necrosis as a post COVID-19 complication.BMC medical genomics · 2024Article
- The association between blood vitamin E and blood pressure in an adult population with and without diabetes mellitus.Frontiers in endocrinology · 2024Article
- Hydroxytyrosol and Arginine as Antioxidant, Anti-Inflammatory and Immunostimulant Dietary Supplements for COVID-19 and Long COVID.Foods (Basel, Switzerland) · 2023Review
- NOS3 (rs61722009) gene variants testing in prediction of COVID-19 pneumonia severity.Nitric oxide : biology and chemistry · 2023Article
- The Renin-Angiotensin-Aldosterone System, Nitric Oxide, and Hydrogen Sulfide at the Crossroads of Hypertension and COVID-19: Racial Disparities and Outcomes.International journal of molecular sciences · 2022Review
- Ginkgo biloba in the management of the COVID-19 severity.Archiv der Pharmazie · 2022Review
- Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review.Antioxidants (Basel, Switzerland) · 2022Review
- Angiotensin II Exaggerates SARS-CoV-2 Specific T-Cell Response in Convalescent Individuals following COVID-19.International journal of molecular sciences · 2022Article
- Recent advances on endogenous gasotransmitters in inflammatory dermatological disorders.Journal of advanced research · 2022Review
- Investigation ofPathogens and global health · 2022Article
- Thrombocytopenia in COVID‑19 and vaccine‑induced thrombotic thrombocytopenia.International journal of molecular medicine · 2022Article
- Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Nrf2 activator PB125® as a carnosic acid-based therapeutic agent against respiratory viral diseases, including COVID-19.Free radical biology & medicine · 2021Review
- GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism.Trends in endocrinology and metabolism: TEM · 2021Review
- Soluble Angiotensin Converting Enzyme 2 (ACE2) Is Upregulated and Soluble Endothelial Nitric Oxide Synthase (eNOS) Is Downregulated in COVID-19-induced Acute Respiratory Distress Syndrome (ARDS).Pharmaceuticals (Basel, Switzerland) · 2021Article
- COVID-19 Disease Severity and Death in Relation to Vitamin D Status among SARS-CoV-2-Positive UAE Residents.Nutrients · 2021Observational
- Kinins and chymase: the forgotten components of the renin-angiotensin system and their implications in COVID-19 disease.American journal of physiology. Lung cellular and molecular physiology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The COVID-19 pandemic poses an imminent threat to humanity, especially to the elderly. The molecular mechanisms underpinning the age-dependent disparity for disease progression is not clear. COVID-19 is both a respiratory and a vascular disease in severe patients. The damage endothelial system provides a good explanation for the various complications seen in COVID-19 patients. These observations lead us to suspect that endothelial cells are a barrier that must be breached before progression to severe disease. Endothelial intracellular defences are largely dependent of the activation of the interferon (IFN) system. Nevertheless, low type I and III IFNs are generally observed in COVID-19 patients suggesting that other intracellular viral defence systems are also activated to protect the young. Intriguingly, Nitric oxide (NO), which is the main intracellular antiviral defence, has been shown to inhibit a wide array of viruses, including SARS-CoV-1. Additionally, the increased risk of death with diseases that have underlying endothelial dysfunction suggest that endothelial NOS-derived nitric oxide could be the main defence mechanism. NO decreases dramatically in the elderly, the hyperglycaemic and the patients with low levels of vitamin D. However, eNOS derived NO occurs at low levels, unless it is during inflammation and co-stimulated by bradykinin. Regrettably, the bradykinin-induced vasodilation also progressively declines with age, thereby decreasing anti-viral NO production as well. Intriguingly, the inverse correlation between the percentage of WT eNOS haplotype and death per 100K population could potentially explain the disparity of COVID-19 mortality between Asian and non-Asian countries. These changes with age, low bradykinin and NO, may be the fundamental reasons that intracellular innate immunity declines with age leading to more severe COVID-19 complications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.