ReviewRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2021
Nrf2 activation putatively mediates clinical benefits of low-dose radiotherapy in COVID-19 pneumonia and acute respiratory distress syndrome (ARDS): Novel mechanistic considerations.
Review in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 3 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- A Systematic Review and Meta-Analysis of Low Dose Radiation Therapy for COVID-19 Pneumonia: Learnings of 4 Years Since Pandemic.Clinical and translational science · 2025Pooled it
- Low-Dose Whole Lung Irradiation for Treatment of COVID-19 Pneumonia: A Systematic Review and Meta-Analysis.International journal of radiation oncology, biology, physics · 2022Pooled it
- Effectiveness of low-dose radiation therapy in COVID-19 patients globally: A systematic review.F1000Research · 2022Pooled it
- Nonlinear Redox-Immune Coupling Under Low-Dose-Rate Radiation: A Compartment-Specific Framework for Biological Responses-A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
- Bronchoalveolar lavage single-cell transcriptomics reveals immune dysregulations driving COVID-19 severity.PloS one · 2025Article
- Cytokine storm in individuals with severe COVID-19 decreases endothelial cell antioxidant defense via downregulation of the Nrf2 transcriptional factor.American journal of physiology. Heart and circulatory physiology · 2023Article
- Low-dose radiotherapy for COVID-19 pneumonia and cancer: summary of a recent symposium and future perspectives.International journal of radiation biology · 2023Article
- Role of the redox state of the Pirin-bound cofactor on interaction with the master regulators of inflammation and other pathways.PloS one · 2023Article
- Comments on "Whole lung irradiation as a novel treatment for COVID-19: Final results of the prospective randomized trial (WINCOVID trial)".Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2022Article
- SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities.Cytokine & growth factor reviews · 2022Review
- Alzheimer's Disease at a Crossroad: Time to Part from Amyloid to More Promising Aspects-Atherosclerosis for a Start.Journal of Alzheimer's disease : JAD · 2022Article
- Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease.Frontiers in microbiology · 2022Review
- COVID-19 and low-dose radiation therapy.Radiation medicine and protection · 2021Review
- Low-dose radiation therapy (LDRT) for COVID-19 and its deadlier variants.Archives of toxicology · 2021Article
- Attenuation of clinical and immunological outcomes during SARS-CoV-2 infection by ivermectin.EMBO molecular medicine · 2021Article
- An Update on the Role of Nrf2 in Respiratory Disease: Molecular Mechanisms and Therapeutic Approaches.International journal of molecular sciences · 2021Review
- The Good and Bad of Nrf2: An Update in Cancer and New Perspectives in COVID-19.International journal of molecular sciences · 2021Review
- Vaccination of cancer patients against COVID-19: towards the end of a dilemma.Medical oncology (Northwood, London, England) · 2021Review
- What Would Become of Nuclear Risk if Governments Changed Their Regulations to Recognize the Evidence of Radiation's Beneficial Health Effects for Exposures That Are Below the Thresholds for Detrimental Effects?Dose-response : a publication of International Hormesis SocietyArticle
- Effect of Low-Dose Gamma Radiation and Lipoic Acid on High- Radiation-Dose Induced Rat Brain Injuries.Dose-response : a publication of International Hormesis SocietyArticle
Corrections and comments
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Authors and funding
6 authors at 6 institutions in 3 countries.
Funding
Abstract
Novel mechanistic insights are discussed herein that link a single, nontoxic, low-dose radiotherapy (LDRT) treatment (0.5-1.0 Gy) to (1) beneficial subcellular effects mediated by the activation of nuclear factor erythroid 2-related transcription factor (Nrf2) and to (2) favorable clinical outcomes for COVID-19 pneumonia patients displaying symptoms of acute respiratory distress syndrome (ARDS). We posit that the favorable clinical outcomes following LDRT result from potent Nrf2-mediated antioxidant responses that rebalance the oxidatively skewed redox states of immunological cells, driving them toward anti-inflammatory phenotypes. Activation of Nrf2 by ionizing radiation is highly dose dependent and conforms to the features of a biphasic (hormetic) dose-response. At the cellular and subcellular levels, hormetic doses of <1.0 Gy induce polarization shifts in the predominant population of lung macrophages, from an M1 pro-inflammatory to an M2 anti-inflammatory phenotype. Together, the Nrf2-mediated antioxidant responses and the subsequent shifts to anti-inflammatory phenotypes have the capacity to suppress cytokine storms, resolve inflammation, promote tissue repair, and prevent COVID-19-related mortality. Given these mechanistic considerations-and the historical clinical success of LDRT early in the 20th century-we opine that LDRT should be regarded as safe and effective for use at almost any stage of COVID-19 infection. In theory, however, optimal life-saving potential is thought to occur when LDRT is applied prior to the cytokine storms and before the patients are placed on mechanical oxygen ventilators. The administration of LDRT either as an intervention of last resort or too early in the disease progression may be far less effective in saving the lives of ARDS patients.
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Registered trials
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