Highlights
- •Recent advances in the pathophysiology of COVID-19 pneumonia provided by autopsies have yielded much more informations as the extensive lung parenchyma damages by the virus, macrophages invasion, some lymphocytes and thrombotic features associated to disseminated life-threatening coagulation disorder.
- •While the hypothetical benefit from a LDR in the treatment symptoms hypotisized by Kirkby C could raise some doubts and disappointed expectations, the propose of the Radiation Induced Lung Injury’s (RILI) model by the Radiotherapy community could contribute to this issue in order to understand the processes and management of this life-threatening disease.
- •Symptoms, radiological CT findings of the chest and histological features occurring in Covid-19 pneumonia seem to mimic the RILI model in all phases of its course. This similarity could help medical community to adopt several effective therapeutic strategies in the treatment of this life-threatening disease.
With regard to the letter written by Kirkby C, investigating a hypothetical benefit of the whole lung low dose radiotherapy (LDRT) to treat COVID-19 pneumonia, several considerations should be examined in light of the recent advances in the pathophysiology of COVID-19 pneumonia provided by autopsies [
[1]
].As a result, a massive lung parenchyma destruction by the virus, macrophages invasion, so lymphocytes and thrombotic features with disseminated life-threatening coagulation disorder have been reported [
[2]
].The Radiotherapy community could contribute to this issue starting from the well established interactions of the immediate cellular-immune system triggered by ionizing radiation as it occurs in the Radiation Induced lung Injury (RILI) model in order to understand the processes and management of this life-threatening disease [
[3]
]. While the hypothetical benefit from LDRT in palliation symptoms could raise some doubts and disappointed expectations.Symptoms, radiological CT findings of the chest and histological features occurring in COVID-19 pneumonia seem to mimic the RILI model in all phases of its course. As in the RILI, a wide variety of CT findings have been reported in COVID-19 pneumonia: ground glass opacities, consolidation, linear opacities and a crazy-paving pattern to the whited out lung according to the severity of lung parenchyma involvement [
[4]
].By postmortem autopsies in affected patients, destruction of lung alveolar structure with exfoliated pneumocystis I-II, giant macrophages, fibrinous exudate in alveolar cavity, thrombosis in micro vessels, pulmonary tissue hemorrhage and interstitial fibrosis as the result of the direct virus injury have been assessed [
[5]
]. Why use the RILI model for this concern?As the virus, radiation disrupts epithelial and endothelial integrity leading to edema, recruitment of leukocytes, resident activated platelets, immature mesenchymal and endothelial cells, neo-angiogenesis, and a cascade of a self-sustaining cycle of inflammation through three main phases of pulmonary radiation response which mimic the COVID-19 pneumonia process [
[6]
].Following radiation exposure, an increased capillary permeability occurs contributing to pulmonary edema. In turn, damage to type I and II pneumocytes leads to loss of surfactant and transudation of serum proteins into the alveoli. Later, cytokines (e.g. Il-1, IL-6, IFNγ, TNF), growth factors (VEGF, FGF) released from damaged lung cells attract inflammatory cells like activated macrophages, resident platelets and mesenchymal lung cells to the alveoli and pulmonary interstitium, inducing an acute pneumonitis which could evolve into ARDS syndrome or fibrosis [
[7]
]. Applying this model to explain the COVID-19 pneumonia development, a targeted therapy and tailored gentler ventilation protocols could be useful to minimize the severity of respiratory failure, as reported in RILI.In the management of RILI, recently drugs directed against the neutrophilis or coagulant activated macrophages and platelets such as sivelestat sodium, nebulized heparin, anti-Cox2, multikinase inhibitors have been tested with promising results [
8
, 9
]. The hypothesis of the potential benefit of LDRT in COVID-19 pneumonia is a fascinating theory but it arises by empirical experiences of the past, while the RILI model has certain established mechanisms and current solutions that can draw the whole medical community’s attention to the fight against COVID-19 pneumonia.Conflict of interest
The authors declare no conflict of interest.
References
- Is low dose radiation therapy a potential treatment for COVID-19 pneumonia?.Radioth Oncol. 2020; 147: 221
- A pathological report of three COVID-19 cases by minimally invasive autopsies.Chin J Path. 2020; 49: E009
- Radiation-induced lung injury assessment and management.Chest. 2019; 156: 150-162
- Chest CT manifestation of new Coronavirus disease (COVID-19): a pictorial review.Eur Radiol. 2020; 19: 1-9
- Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer.J Thorac Oncol. 2020; 20: 30132-30135
- The pathogenesis of radiation-induced lung damage.Lung. 1981; 159: 115-125
- The cellular and molecular mechanism of radiation-induced lung injury.Med Sci Monit. 2017; 23: 3446-3450
- Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.BMC Pulm Med. 2017; 17: 148-156
- Role of heparin in pulmonary cell populations in an in-vitro model of acute lung injury.Resp Res. 2017; 18: 89-100
Article info
Publication history
Published online: May 07, 2020
Accepted:
April 18,
2020
Received:
April 16,
2020
Footnotes
☆The Editors of the Journal, the Publisher and the European Society for Radiotherapy and Oncology (ESTRO) cannot take responsibility for the statements or opinions expressed by the authors of these articles. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. For more information see the editorial “Radiotherapy & Oncology during the COVID-19 pandemic”, Vol. 146, 2020.
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© 2020 Elsevier B.V. All rights reserved.
