Low Dose Radiation Therapy for Covid-19 Pneumonia

There is no specific antiviral treatment recommended for COVID-19, and no vaccine is
currently available. The treatment is symptomatic, and oxygen therapy represents the major
treatment intervention for patients with severe infection. Mechanical ventilation may be
necessary in cases of respiratory failure refractory to oxygen therapy, whereas hemodynamic
support is essential for managing septic shock. The death rate ranges from 2-15% in different
group of patients.

COVID-19 pandemic is unprecedented in modern history of humankind and it has become
imperative to find novel treatments to mitigate the casualties caused by infection. The
clinical spectrum of COVID-19 varies from mild symptoms to critical conditions requiring
ventilatory support and ICU care. According to Chinese CDC report, 81% patients had mild
disease (non-pneumonia and mild pneumonia), 14% had severe disease and 5% had critical
disease. Based on severity of symptoms, there are several scoring methods which can predict
the outcome of disease. National early warning score (NEWS) is a popular scoring system used
for non-ICU patients suffering from acute illness. This score helps in quickly determining
the degree of illness and intervention required. It also provides likelihood of death or
admission to an ICU. Based on this score any illness can be categorized as mild (Score <4),
moderate (Score 5-6 or individual 3) and severe (Score ≥7). According to this scoring system,
Covid-19 patients having a score of 5-6 will have probability of 15.7% critical events
(HDU/ICU admission or 30-day mortality) and those having score ≥7 will have about 24.1%
critical events.

The pathogenesis of COVID-19 pneumonitis appears to involve a cytokine storm with elevated
pro- inflammatory cytokines such as IL-6 and TNFα among many others, leading to an onslaught
of neutrophils and macrophages, diffuse alveolar damage and respiratory failure. This is
where a potential opportunity for low-dose radiation therapy (LDRT) emerges. LDRT is a
potential treatment for COVID-19 pneumonia since it has an anti-inflammatory action.
Successful management of worsening pneumonia will reduce the development of ARDS and thereby
preventing deaths.

Availability of megavoltage beam in modern times has improved our dosimetry in treating deep
targets. Radiotherapy which can penetrate lobar and interstitial space can help in preventing
both lobar as well as interstitial pneumonia. In the absence of any effective drug and,
historical data suggests that low dose of 0.5 to 1 Gy radiotherapy to whole lung can possibly
prevent cytokine storm and critical events (ICU admission, mechanical ventilation or death).

The initial use of X-rays to treat patients with pneumonia was reported in 1907. This report
offered a new mechanistic insight founded on the dose response, proposing that low doses of
X-rays would affect disease resolution. It was observed that not only did the X-ray treatment
has lifesaving potential, but it was also effective when other treatments had reached their
therapeutic limits as seen in cases of chronic bronchopneumonia, which could be resolved with
a single administration of X-rays. Subsequent reports suggested that LDRT was successful in
decreasing the mortality rate in untreated patients from about 30% to 5-10%.

Rationale for the Study: It is reasonable to try an LDRT treatment of 30 to 100 cGy to the
lungs of a patient with COVID-19 pneumonia as it could reduce the inflammation and relieve
the life-threatening symptoms. The recent emerging literature indicates that the efficacy of
thoracic LDRT must be investigated as it would present a negligible risk to COVID-19
pneumonia patients, and have the potential to reduce the fatality rates.

Study Design: Interventional, Clinical, Single arm, Pilot study Number of patients: 10
Treatment: Patient will be treated as per COVID-19 standard management protocol of the
treating institute along with intervention of Low Dose Radiotherapy (LDRT) 70cGy in single
fraction.

Treatment field- Field adequately covering both the lungs. Beam energy : 6MV X-ray photons
Number of beams- 2 (1 Anterior and 1 posterior field). Prescription point - Midway of
anterior-posterior chest separation. Treatment Workflow: Patients will be maneuvered to lie
down on treatment couch in a supine position, with hands above head. Gantry rotated to 90
degree, a lateral chest X ray portal image will be taken, which will guide in measuring dose
prescription point. Gantry rotated back to 0 degree; an adequate field size will be opened.
Total treatment duration will be about 20-30 minutes.

Response Assessment and statistical analysis: Response will be assessed based on the
symptomatic improvement or deterioration by using the NEWS score. The NEWS score will be
recorded on baseline and then on Day 3 (D-3), Day 7 (D-7) and Day 14 (D-14). To compare the
NEWS score (baseline and post LDRT), student t test (paired) will be used. For statistical
significance, p value of 0.1 will be considered significant. Number of patients requiring ICU
admission or undergoing death following LDRT will also be recorded to assess critical events.