Low dose radiation therapy as a potential life saving treatment for COVID-19-induced acute respiratory distress syndrome (ARDS)

Gaurav Dhawan, Rachna Kapoor, Rajiv Dhawan, Ravinder Singh, Bharat Monga, James Giordano, Edward J Calabrese, Gaurav Dhawan, Rachna Kapoor, Rajiv Dhawan, Ravinder Singh, Bharat Monga, James Giordano, Edward J Calabrese

Abstract

The new coronavirus COVID-19 disease caused by SARS-CoV-2 was declared a global public health emergency by WHO on Jan 30, 2020. Despite massive efforts from various governmental, health and medical organizations, the disease continues to spread globally with increasing fatality rates. Several experimental drugs have been approved by FDA with unknown efficacy and potential adverse effects. The exponentially spreading pandemic of COVID-19 deserves prime public health attention to evaluate yet unexplored arenas of management. We opine that one of these treatment options is low dose radiation therapy for severe and most critical cases. There is evidence in literature that low dose radiation induces an anti-inflammatory phenotype that can potentially afford therapeutic benefit against COVID-19-related complications that are associated with significant morbidity and mortality. Herein, we review the effects and putative mechanisms of low dose radiation that may be viable, useful and of value in counter-acting the acute inflammatory state induced by critical stage COVID-19.

Keywords: Acute Respiratory Distress Syndrome (ARDS); Anti-inflammatory phenotype; COVID-19; Cytokine storm; Hormesis; Low dose radiotherapy.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
Radiation dose and macrophage polarization (adapted from: Genard et al. , Calabrese et al. , Pinto et al. [38]).

References

    1. Cascella M, Rajnik M, Cuomo A, et al. Features, Evaluation and Treatment Coronavirus (COVID-19) [Updated 2020 Mar 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Available from: .
    1. Zhou L, Zhang M, Wang J, Gao J. Sars-Cov-2: Underestimated damage to the nervous system. Tropical Medicine and Infectious Disease (101642) (2020). Available from: 10.1016/j.tmaid.2020.101642.
    1. American Thoracic Society, Chapter 2 Acute Respiratory Distress Syndrome .
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Yang P., Wang X. COVID-19: a new challenge for human beings. Cell Mol Immunol. 2020 doi: 10.1038/s41423-020-0407-x.
    1. Hussin A Rothan, Siddappa N Byrareddy. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmunity (2020), 102433, ISSN 0896-8411, .
    1. Yonggang Zhou, Binqing Fu, Xiaohu Zheng, Dongsheng Wang, Changcheng Zhao, Yingjie qi, Rui Sun, Zhigang Tian, Xiaoling Xu, Haiming Wei, Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients, National Science Review, nwaa041, .
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 doi: 10.1001/jama.2020.1585.
    1. Shi Y., Wang Y., Shao C. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020 doi: 10.1038/s41418-020-0530-3.
    1. Vaduganathan M., Vardeny O., Michel T. Renin–angiotensin–aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020
    1. Hamming I., Timens W., Bulthuis M.L., Lely A.T., Navis G., van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–637.
    1. Cheng Y., Luo R., Wang K. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 doi: 10.1016/j.kint.2020.03.005.
    1. Madsbad S. COVID-19 Infection in people with diabetes. Touch Endocrinol (2020). .
    1. Siddiqi H.K. COVID-19 illness in native and immunosuppressed states: a clinical–therapeutic staging proposal. J Heart Lung Transplant. 2020;39 doi: 10.1016/j.healun.2020.03.012.
    1. Calabrese E.J., Dhawan G. How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med. 2013;86:555–570.
    1. Calabrese E.J., Dhawan G., Kapoor R. The use of X-rays in the treatment of bronchial asthma: a historical assessment. Radiat Res. 2015;184:180–192.
    1. Calabrese E.J., Dhawan G., Kapoor R., Kozumbo W.J. Radiotherapy treatment of human inflammatory diseases and conditions: optimal dose. Hum Exp Toxicol. 2019;38:888–898.
    1. Hildebrandt G., Seed M.P., Freemantle C.N., Alam C.A.S., Colville-Nash P.R., Trott K.R. Mechanisms of the anti-inflammatory activity of low-dose radiation therapy. Int J Radiat Biol. 1998;74:367–378.
    1. Schaue D., Jahns J., Hildebrandt G., Trott K.R. Radiation treatment of acute inflammation in mice. Int J Radiat Biol. 2005;81:657–667.
    1. Nakatsukasa H., Tsukimoto M., Ohshima Y., Tago F., Masada A., Kojima S. Suppressing effect of low-dose gamma-ray irradiation on collagen-induced arthritis. J Radiat Res. 2008;49:381–389.
    1. Kern P., Keilholz L., Forster C., Seegenschmiedt M.H., Sauer R. In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol. 1999;75:995–1003.
    1. Huynh M.L.N., Fadok V.A., Henson P.M. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-β1 secretion and the resolution of inflammation. J Clin Invest. 2002;109:41–50.
    1. Ren Y., Xie Y., Jiang G., Fan J., Yeung J., Li W. Apoptotic cells protect mice against lipopolysaccharide-induced shock. J Immunol. 2008;180:4978–4985.
    1. DosReis G.A., Lopes M.F. The importance of apoptosis for immune regulation in Chagas disease. Mem Inst Oswaldo Cruz. 2009;104(Suppl 1):259–262.
    1. Ferri L.A., Maugeri N., Rovere-Querini P., Calabrese A., Ammirati E., Cianflone D. Anti-inflammatory action of apoptotic cells in patients with acute coronary syndromes. Artherosclerosis. 2009;205:391–395.
    1. Perruche S., Saas P., Chen W. Apoptotic cellmediated suppression of streptococcal cell wall-induced arthritis is associated with alteration of macrophage function and local regulatory T-cell increase: a potential cellbased therapy? Arthritis Res Ther. 2009;11(4):R104.
    1. Esmann L., Idel C., Sarkar A., Hellberg L., Behnen M., Möller S. Phagocytosis of apoptotic cells by neutrophil granulocytes: diminished proinflammatory neutrophil functions in the presence of apoptotic cells. J Immunol. 2010;184:391–400.
    1. Nakatsukasa H., Tsukimoto M., Tokunaga A., Kojima S. Repeated y irradiation attenuates collagen-induced arthritis via up-regulation of regulatory T cells but not by damaging lymphocytes directly. Radiat Res. 2010;174:313–324.
    1. Weng L., Williams R.U., Vieira P.L., Screaton G., Feldmann M., Dazzi F. The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity. Ann Rheum Dis. 2010;69:1519–1526.
    1. Arenas M., Gil F., Gironella M., Hernandez V., Jorcano S., Biete A. Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice. Int J Radiat Oncol Biol Phys. 2006;66:560–567.
    1. Arenas M., Gil F., Gironella M., Hernández V., Biete A., Pique J.M. Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-β1 expression. Radiother Oncol. 2008;86:399–406.
    1. Frey B., Gaipl U.S., Sarter K., Zaiss M.M., Stillkrieg W., Rödel F. Whole body low dose irradiation improves the course of beginning polyarthritis in human TNF-transgenic mice. Autoimmunity. 2009;42:346–348.
    1. Calabrese E.J., Calabrese V. Reduction of arthritic symptoms by low dose radiation therapy (LD-RT) is associated with an anti-inflammatory phenotype. Int J Radiat Biol. 2013;89:278–286.
    1. Abd El-fatah H.A.E., Ezz M.K., El-kabany H.A. Reduction of some extra-articular complications associated with arthritis development in rats by low dose γ-irradiation. Arab J Nucl Sci Appl. 2020;53:172–181.
    1. Genard G., Lucas S., Michiels C. Reprogramming of tumor-associated macrophages with anticancer therapies: Radiotherapy versus chemo- and Immunotherapies. Front Immunol. 2017;8:828.
    1. Klug F., Prakash H., Huber P. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell. 2013;24:589–602.
    1. Calabrese E.J., Giordano J.J., Kozumbo W.J. Hormesis mediates dose sensitive shifts in macrophage activation patterns. Pharm Res. 2018;137:236–249.
    1. Pinto A.T., Pinto M.L., Cardoso A.P. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities. Sci Rep. 2016;6:18765.
    1. Calabrese E.J., Dhawan G. The role of x-rays in the treatment of gas gangrene: a historical assessment. Dose-Response. 2012;10:626–643.
    1. Calabrese E.J., Dhawan G. The historical use of radiotherapy in the treatment of sinus infections. Dose Res. 2013;11:469–479.
    1. Calabrese E.J., Dhawan G. Historical use of x-rays: treatment of inner ear infections and prevention of deafness. Hum Exper Toxicol. 2014;33(5):542–553.
    1. Calabrese E.J., Dhawan G., Kapoor R. Use of X-rays to treat shoulder tendonitis/bursitis: a historical assessment. Arch Toxicol. 2014;88:1503–1517.
    1. Calabrese E.J., Dhawan G., Kapoor R. Radiotherapy for pertussis: an historical assessment. Dose Response. 2017;15(2):1–9. doi: 10.1177/1559325817704760.
    1. Dhawan G., Kapoor R., Dhamija A., Singh R., Monga B., Calabrese E.J. Necrotizing fasciitis: low-dose radiotherapy as a potential adjunct treatment. Dose-Response. 2019;17:1–6.
    1. Calabrese E.J. X-ray treatment of carbuncles and furuncles (boils): a historical assessment. Hum Exper Toxicol. 2013;32:817–827.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe