ArticleAmerican journal of physiology. Heart and circulatory physiology2023
Cytokine storm in individuals with severe COVID-19 decreases endothelial cell antioxidant defense via downregulation of the Nrf2 transcriptional factor.
Article in American journal of physiology. Heart and circulatory physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- The association between Helicobacter pylori infection and diabetes mellitus: an updated meta-analysis of 45 case-control studies.Journal of health, population, and nutrition · 2025Pooled it
- Adipose-derived stem cells-conditioned medium (ADMSCs-CM) improves testicular function and sperm DNA damage via Nrf2 antioxidant signaling pathways in rat unilateral varicocele.Stem cell research & therapy · 2026Article
- Retinal microvascular alterations consistent with endothelial dysregulation in paediatric post-COVID-19 syndrome: A prospective matched-cohort study.Scientific reports · 2026Article
- Convergent innate immune and regulated cell-death pathways in selected myopathies.Frontiers in immunology · 2026Review
- Systemic Immune-Inflammation Index and Risk of Diabetes and Prediabetes Two Years Post-COVID-19: A Retrospective Cohort Study.Medical journal of the Islamic Republic of Iran · 2026Article
- Involvement of oxidative stress in post-acute sequelae of COVID-19: clinical implications.Redox report : communications in free radical research · 2025Article
- Endothelial cell source dictates the expression and release of fibrinolytic markers in a proinflammatory environment.Research and practice in thrombosis and haemostasis · 2025Article
- Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review.Frontiers in immunology · 2025Review
- The fibrin-derived peptide FX06 protects human pulmonary endothelial cells against the COVID-19-triggered cytokine storm.Frontiers in immunology · 2025Article
- A narrative review on lung injury: mechanisms, biomarkers, and monitoring.Critical care (London, England) · 2024Review
- Immunity and Coagulation in COVID-19.International journal of molecular sciences · 2024Review
- Anti-Inflammatory Therapeutic Mechanisms of Isothiocyanates: Insights from Sulforaphane.Biomedicines · 2024Review
- Selective Impact of Selenium Compounds on Two Cytokine Storm Players.Journal of personalized medicine · 2023Article
- Article
- Host mitochondria: more than an organelle in SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The cytokine storm in SARS-CoV-2 infection contributes to the onset of inflammation and target-organ damage. The endothelium is a key player in COVID-19 pathophysiology and it is an important target for cytokines. Considering that cytokines trigger oxidative stress and negatively impact endothelial cell function, we sought to determine whether serum from individuals with severe COVID-19 decreases endothelial cells' main antioxidant defense, i.e., the antioxidant transcriptional factor Nrf2. Human umbilical vein endothelial cells (HUVECs) were incubated with serum from patients with severe COVID-19 at different time points and the effects on redox balance and Nrf2 activity were determined. Serum from individuals with COVID-19 increased oxidant species, as indicated by higher DHE (dihydroethydine) oxidation, increased protein carbonylation, and induced mitochondrial reactive oxygen species (ROS) generation and dysfunction. Serum from patients with COVID-19, but not serum from healthy individuals, induced cell death and diminished nitric oxide (NO) bioavailability. In parallel, Nrf2 nuclear accumulation and the expression of Nrf2-targeted genes were decreased in endothelial cells exposed to serum from individuals with COVID-19. In addition, these cells exhibited higher expression of Bach-1, a negative regulator of Nrf2 that competes for DNA binding. All events were prevented by tocilizumab, an IL-6 receptor blocker, indicating that IL-6 is key to the impairment of endothelial antioxidant defense. In conclusion, endothelial dysfunction related to SARS-CoV-2 infection is linked to decreased endothelial antioxidant defense via IL-6-dependent mechanisms. Pharmacological activation of Nrf2 may decrease endothelial cell damage in individuals with severe COVID-19.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.