No abstract

The COVID-19 outbreak is affecting people worldwide. Many infected patients have respiratory involvement that may progress to acute respiratory distress syndrome. This pilot study aimed to evaluate the clinical efficacy of low-dose whole-lung radiation therapy in patients with COVID-19 pneumonia. Methods and Materials: In this clinical trial, conducted in Iran, we enrolled patients with COVID-19 who were older than 60 years and hospitalized to receive supplementary oxygen for their documented pneumonia. Participants were treated with whole-lung irradiation in a single fraction of 0.5 Gy plus the national protocol for the management of COVID-19. Vital signs (including blood oxygenation and body temperature) and laboratory findings (interleukin-6 and C-reactive peptide) were recorded before and after irradiation. Results: Between May 21, 2020 and June 24, 2020, 5 patients received whole-lung irradiation. They were followed for 5 to 7 days to evaluate the response to treatment and toxicities. The clinical and paraclinical findings of 4 of the 5 patients (patient 4 worsened and died on day 3) improved on the first day of irradiation. Patient 3 opted out of the trial on the third day after irradiation. The mean time to discharge was 6 days for the other 3 patients. No acute radiation-induced toxicity was recorded. Conclusions: With a response rate of 80%, whole-lung irradiation in a single fraction of 0.5 Gy had encouraging results in oxygen-dependent patients with COVID-19 pneumonia.

Introduction Radiotherapy (RT) -commonly employed in cancer management- has been considered as one of the potential treatments for COVID-19 pneumonia. Here, we present the results of the pilot trial evaluating low-dose whole-lung irradiation (LD-WLI) in patients with COVID-19 pneumonia. Methods Ten patients with moderate COVID-19 pneumonia were treated with LD-WLI in a single fraction of 0.5 or 1.0 Gy along with the national protocol. The primary endpoint was the improvement in SpO 2 . The secondary endpoints were the number of hospital/ICU stay days, the number of intubations after RT, 28-day mortality, and changes in biomarkers. The response rate (RR) was defined as a rise in SpO 2 upon RT with a rising or constant trend in the next 2 days, clinical recovery (CR) included patients who were discharged or acquired SpO 2 ≥93% on room air, and 28-day mortality rate was defined based on RT day. Results The median age was 75 years (80% male). Five, 1, and 4 patients received single 0.5Gy, two 0.5Gy, and single 1.0Gy LD-WLI, respectively. The mean improvement in SpO 2 at days 1 and 2 after RT was 2.4% (±4.8%) and 3.6% (±6.1%), respectively, with improvement in 9 patients after 1 day. Five, 1, and 4 patients were discharged, opted out the trial, and died in hospital, respectively. Two of 5 discharged patients died within 3 days at home. Among discharged patients, the SpO 2 at discharge was 81-88% in 3 and 93% in the other 2 patients. Overall, the RR and CR were 63.6% and 55.5%, respectively. The RR, CR, and 28-day mortality of single 0.5Gy- and 1.0Gy-WLI were 71.4 vs. 50% ( p = 0.57), 60 vs. 50% ( p = 0.64), and 50 vs. 75% ( p = 0.57), respectively. Conclusion LD-WLI with a single 0.5 Gy or 1 Gy-fraction is feasible. A randomized trial with patients that do not receive radiation is required to assess efficacy of LD-WLI for COVID-19.

Bronchiolitis obliterans with organizing pneumonia (BOOP) is an infrequently encountered clinical condition that can mimic a number of other pathologic lung processes. The presentation of this treatable condition in cancer patients has not been described in any large series. We conducted a retrospective study of patients with BOOP at Memorial Sloan-Kettering Cancer Center, NewYork, NY, U.S.A. from January 1992 to December 1999. The type and treatment of primary cancer, clinical and radiographic features of initial BOOP presentation, and outcome following therapy were recorded. Forty-three patients with an underlying diagnosis of cancer were found on lung biopsy to have BOOP as an isolated entity. BOOP was encountered in patients with a variety of clinical presentations, and many types of malignancies. The symptom patterns were non-specific, as were the physiological abnormalities. The only clear relationship between the underlying malignancyand the diagnosis of BOOP at presentation was in the chest radiographic findings. Patients with solid organ tumors were more likely to have nodular or mass like radiographic abnormalities (81%) than to have diffuse infiltrates (19%). We observed the opposite pattern in patients with hematologic malignancies (22% vs.67%). The vast majority of patients recovered from this condition. In conclusion, For cancer patients, BOOP represents a treatable cause of lung disease with protean manifestations. BOOP can mimic pulmonary malignancy and pulmonary infection. In cancer patients, the evaluation of new pulmonary symptoms accompanied by radiographic changes should include a consideration of this diagnosis.

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10–5.17, P-value = 0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63–3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI=1.10-5.17, P-value=0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI=0•63-3•16, P-value=0•395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies. Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768)

No abstract

No abstract