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 Table of Contents  
EDITORIAL
Year : 2020  |  Volume : 11  |  Issue : 1  |  Page : 1-2

Stalling cytokine storm in patients with COVID-19 infection with low-dose radiation


Chief Radiation Oncologist, Advanced Center for Radiation Oncology, Dr. Balabhai Nanavati Hospital, S. V. Road, Vile Parle (W), Mumbai, India

Date of Submission11-May-2020
Date of Acceptance12-May-2020
Date of Web Publication04-Jun-2020

Correspondence Address:
Dr. Nagraj Gururaj Huilgol
Chief Radiation Oncologist, Advanced Center for Radiation Oncology, Dr. Balabhai Nanavati Hospital, S. V. Road, Vile Parle (W), Mumbai - 400 056
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrcr.jrcr_23_20

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How to cite this article:
Huilgol NG. Stalling cytokine storm in patients with COVID-19 infection with low-dose radiation. J Radiat Cancer Res 2020;11:1-2

How to cite this URL:
Huilgol NG. Stalling cytokine storm in patients with COVID-19 infection with low-dose radiation. J Radiat Cancer Res [serial online] 2020 [cited 2022 Aug 17];11:1-2. Available from: https://www.journalrcr.org/text.asp?2020/11/1/1/285986



The novel coronavirus, now named COVID-19, is known to cause lower respiratory tract-related changes including pneumonia. In severe cases, patients develop acute respiratory syndrome (ARDS) and multiple organ failure. Even though lung is the primary organ which gets affected, it is now assumed that the infection with COVID-19 is a systematic disease. Overexpression of pro-inflammatory cytokines, for example interleukin (IL)-1β, IL-6, interferon-γ, interferon-inducible protein-10, monocyte chemoattractant protein-1 (MNP-1), granulocyte colony-stimulating factor, macrophage inflammatory protein-1 (MIP-12), and tumour necrosis protein (TNP), is seen in patients with ARDS. This overexpression of cytokines and chemokines is called “cytokine storm.” This overexpression of pro-inflammatory cytokines is at the heart of the significant morbidity and mortality in patients with ARDS with or without cardiac toxicity.[1]

The pathophysiology of COVID-19 infection is marked by aggressive inflammatory response leading to airway damage. Viral infection of lower respiratory lining and destruction of lung cells trigger local immune response, recruiting macrophages and monocytes that respond to infection. Release of cytokines and prime adaptive T and B cell immune response follows. Generally, this immune response that is mounted following infection helps the host to resolve the infection. In an event of dysregulation and an overdrive of the immune response, ARDS and cardiac events follow.[2]

Effective measures to stall the cytokine storm may help in preventing ARDS and cardiac toxicity. Steroid, oxygen therapy, anti-inflammatory and supportive treatment are administrated to treat COVID-19 infection. The fatality rate is still very high once ARDS sets in. Any novel approach to mitigate ARDS needs exploration as mortality in the elderly and those with co-morbidities remains a challenge.[3]

Charles Kirkby and Marc Mackneries in a letter to the editor of Radiotherapy and Oncology Journal, has proposed administration of low-dose radiotherapy as a potential treatment for COVID-19-related pneumonia. The proposal is to deliver 70–100 cGy or 0.07–2 Gy to the chest region. The inspiration for this proposal comes from the historical use of ionizing radiation for pneumonia.

Historically, Powel E.V. in 1936 and Oppenhimer A in 1943 reported favorable outcome following radiation of chest. The dose was expressed in skin erythema dose. The practice of radiation therapy for pneumonia did not find favour once sulphonamides were used in the management of pneumonia.[4]

Calabrese in his review of low-dose irradiation for pneumonia (LDR) has reported a beneficial effect in 85%of patients. This was a complication of 15 studies. Patients on an average received 50 R. The proposed mechanism of action (LDR) is induction of anti-inflammatory phenotype, which facilitates reversal of clinical symptom and disease resolution.

Radiation for immunosuppression has been reported earlier in the literature. Local radiation of grafted kidney and occasionally of the heart was practiced to prevent or treat acute or hyperacute rejection. A low dose of 100–600 rads was delivered daily or on alternate days. A success rate of 36% was reported by Levitt et al. in preventing rejection.[5] Whan Clayton and Hess have initiated Phase I/II study at Emory Winship Cancer Institute. As of April 54, 2020, two patients were recruited. outcomes are awaited.

Biphasic response to radiation or drugs is a less appreciated phenomenon. Radiophobia following nuking of Japan led to the suppression of low-dose radiation for therapeutic purposes. The linear no-threshold model (LNT) fails to acknowledge a differential effect of radiation at various dose levels. It overlooks the biphasic nature of response. It is based on the assumption of proportionality of dose, and dose response, across the spectrum of 0.001–100 Gy of radiation. It is premised on the hypothesis that double-strand breaks have a linear relation at all dose levels for inducing cell transformation and mutations, besides the induction of cancer. The proponents of non-LNT model propose a two-step dose response. That is proposing a threshold below which biological responses to radiation are distinct from higher dose of radiation. For instance, radiation at lower doses is anti-inflammatory, whereas it is pro-inclinatory at higher doses. Low-dose radiation with its anti-inflammatory effect may prevent the emergence of ARDS and reduce the chances of mortality. The forthcoming phase trial initiated by Magrini and Tomasini has started recruiting patients for Phase I study. It is a pilot study on the feasibility of low-dose radiotherapy of SARS-COV-2 pneumonitis (COVID-19-low-dose radiotherapy – COLOR-19). The estimated date of completion is July 2020. The study aims to look at the feasibility of low-dose radiation and reduction of intensive care admissions. The secondary endpoints are variations in the Brescia Respiratory COVID-19 Severity -Scale after low dose radiation on 3, 6, and 10 days. Evaluation of safety and tolerance of low-dose radiation therapy and variation of the chest X-ray radiological findings according to Brixia scoring system. This important trial will not only help patients with COVID-19, but also establish a biphasic response to radiation as an important biological phenomenon.



 
  References Top

1.
Wansili Q, Fans LV, Zhang X, Guo Lang C, Xiao Q, Xiok Y, et al. Characteristics of lymphocyte response and cytokine profiles in the peripheral blood of SARS- COV- 2 infected patients. Med Review 2020.02.16. 20023671; 2020.  Back to cited text no. 1
    
2.
Tay MZ, Poh CM, Rénia L, Mac Ary PA, Ng L7P. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-020-0311-8.  Back to cited text no. 2
    
3.
Kirkby C, Mackenzie M. -Is low dose radiation therapy a potential treatment for COVID-19 pneumonia?, Radiotherapy and Oncology, https://doi.org/10.1016/j.radonc.2020.04.004.  Back to cited text no. 3
    
4.
Calabrese EJ, Dhawan G. How radiotherapy was historically used to treat pneumonia: Could it be used today? Yale Y Biol Med 2013;86:555-70.  Back to cited text no. 4
    
5.
Levitt SH, Royster RL, O'Foughludha FT, Wolf JS, Lower RR, King ER, et al. Radiation for immunosuppression in human organ transplantation. II. Clinical experience. Acta Radiol Ther Phys Biol 1971;10:329-40.  Back to cited text no. 5
    




 

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