Low-Dose Radiation Therapy in COVID-19 Pneumonia

Low-dose radiation therapy (LDRT) has re-emerged as a potential treatment for COVID-19 pneumonia by harnessing its anti-inflammatory properties to mitigate severe pulmonary injury. Historically applied in the early 20th century for bacterial and viral pneumonias, LDRT at single-fraction doses below 1 Gy appears to interrupt the self-amplifying cycle of pro-inflammatory cytokine release, vascular leakage and alveolar damage that underpins acute respiratory distress syndrome (ARDS). Preclinical models have shown that targeted low doses induce early production of immunoregulatory mediators—most notably transforming growth factor-β (TGF-β)—promoting alternative (M2) macrophage activation, reducing neutrophil infiltration and lowering levels of interleukin-6 and tumour necrosis factor. Early-phase clinical experiences, predominantly in elderly or comorbid cohorts unsuited to intensive care, report rapid improvements in oxygenation, declines in C-reactive protein and interleukin-6, and acceptable short-term safety profiles. While these signals of efficacy and tolerability have stimulated global interest, critical questions remain regarding optimal dose, timing relative to disease onset, selection criteria and potential late effects. Well-designed randomised trials are under way to define the role of LDRT within the broader therapeutic arsenal against COVID-19 pneumonia.

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Low-Dose Radiation Therapy in COVID-19 Pneumonia publication trend

The graph below shows the total number of articles in low-dose radiation therapy in covid-19 pneumonia across all publications each year (not limited to Nature Index journals).

Technical terms

Low-dose radiation therapy (LDRT): Delivery of ionising radiation at total doses below 1 Gy per fraction to modulate inflammatory processes rather than to ablate tissue.

Cytokine storm: An excessive and dysregulated release of pro-inflammatory cytokines that can lead to widespread tissue damage and organ dysfunction.

Acute respiratory distress syndrome (ARDS): A severe form of respiratory failure characterised by diffuse alveolar damage, hypoxaemia and reduced lung compliance.

Transforming growth factor-β (TGF-β): A multifunctional cytokine that suppresses pro-inflammatory signals, promotes tissue repair and drives alternative macrophage activation.

M2 macrophages: Alternatively activated macrophages that support resolution of inflammation, tissue remodelling and repair.

Paraoxonase-1 (PON1): An antioxidant enzyme associated with high-density lipoprotein that protects against oxidative stress and modulates inflammatory responses.

References

1. Low-dose radiation therapy suppresses viral pneumonia by enhancing broad-spectrum anti-inflammatory responses via transforming growth factor-β production. Frontiers in Immunology (2023).
2. Low-Dose Radiotherapy for Patients with Pneumonia Due to COVID-19: A Single-Institution Prospective Study. Biomedicines (2023).
3. Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia. Antioxidants (2022).