Pilot Study on the Feasibility of Low Dose Radiotherapy for SARS-Cov-2 Pneumonitis (COVID-19 Low Dose Radiotherapy - COLOR 19)

BACKGROUND

Since the first case of Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) infection and its subsequent clinical manifestation (COronaVIrus Disease 19, COVID-19) in the city of Wuhan (Hubei, China) in December 2019, contagion abruptly spread to different regions of China and, subsequently, to all continents. To date, 1 521 252 cases have been confirmed worldwide. With the first case ascertained in Lombardy at the end of February 2020, Italy soon became the first European country to face the exponential growth in the number of infected people (to date -May 3, 2020-210,717 total cases, currently positive 100,179).The disease turned into an actual health emergency due to the rapid spread and the need of hospitalization and respiratory function support in Intensive Care Unit (ICU) for a significant fraction of the patients. However, the clinical presentation of COVID-19 is non-specific and extremely heterogeneous. Many patients are asymptomatic or exhibit mild symptoms, which include cough, fever, general malaise with myalgias, anosmia and ageusia. The most common changes in blood tests include lymphopenia, thrombocytopenia and increased C-reactive protein and ferritin.

As emerged by clinical data, the viral infection could be divided into three different phases: stage I, asymptomatic incubation period with little or undetectable viral load; stage II, mild symptomatic period with considerable and detectable viral load; stage III, severe symptomatic period with high viral load.

The definitive diagnosis requires a positive molecular test with Real Time PCR (RT-PCR) method for SARS-CoV-2 on nasopharyngeal swab. However, this technique suffers from sub-optimal sensitivity, which may require repetition on bronchoalveolar lavage. The execution of chest CT is therefore essential, as it is characterized by high sensitivity and can detect highly suggestive findings even in patients with negative RT-PCR.

Although the majority of infections resolve spontaneously without the need for specific therapy, up to 20% of patients can develop severe clinical pictures with pneumonia characterized by dyspnea, tachypnea and hypoxemia that requires treatment in a hospital setting. Pulmonary involvement is typically bilateral, peripheral and basal in most cases, presenting on CT scan with multifocal ground glass opacities and interstitial infiltrations; complete resolution usually takes several weeks. Despite active treatment, about 5-10% of cases can precipitate, often suddenly, into critical conditions including respiratory failure, ARDS and multi-organ dysfunction that require ICU admission and are burdened with high mortality.