Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Purpose Phase 1 clinical trials have established low-dose, whole-lung radiation therapy (LD-RT) as safe for patients with coronavirus disease 2019 (COVID-19)-related pneumonia. By focally dampening cytokine hyperactivation, LD-RT may improve disease outcomes through immunomodulation. Methods and Materials Patients with COVID-19-related pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or until hospital discharge, and compared with age- and comorbidity-matched controls meeting identical disease severity criteria. Eligible patients were hospitalized, severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) positive, had radiographic consolidations, and required supplemental oxygen but had not rapidly declined on admission or before drug therapy or LD-RT. Efficacy endpoints were time to clinical recovery, radiographic improvement, and biomarker response. Results Ten patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared with 10 control patients blindly matched by age and comorbidity. Six controls received COVID-19 drug therapies. Median time to clinical recovery was 12 days in the control cohort compared with 3 days in the LD-RT cohort (hazard ratio 2.9, P = .05). Median time to hospital discharge (20 vs 12 days, P = .19) and intubation rates (40% vs 10%, P = .12) in the control and LD-RT cohorts were compared. Median time from admission to recovery was 10 versus 13 days (P = .13). Hospital duration average was 19 versus 22.6 days (P = .53). Average hospital days on supplemental oxygen of any duration was 13.1 versus 14.7 days (P = .69). Average days with a documented fever was 1 versus 4.3 days (P = .12). Twenty-eight–day overall survival was 90% for both cohorts. The LD-RT cohort trended toward superior rates of improved radiographs (P = .12) and delirium (P Conclusions A prospective cohort of predominantly elderly hospitalized patients with COVID-19-related pneumonia were recovered to room air quicker than age- and comorbidity-matched controls, with trending or significant improvements in delirium, radiographs, and biomarkers, and no significant acute toxicity. Low-dose, whole-lung radiation for patients with COVID-19-related pneumonia appears safe and may be an effective immunomodulatory treatment. Larger prospective randomized trials are needed to define the efficacy of LD-RT for COVID-19.

Immunomodulatory Low-Dose Whole-Lung Radiation for Patients with Coronavirus Disease 2019-Related Pneumonia.

PURPOSE/OBJECTIVE: Phase I clinical trials have established low-dose, whole-lung radiotherapy (LD-RT) as safe for patients with COVID-19-related pneumonia. By focally dampening cytokine hyperactivation, LD-RT may improve disease outcomes through immunomodulation. METHODS AND MATERIALS: Patients with COVID-19-related pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or until hospital discharge, and compared to age- and comorbidity-matched controls meeting identical disease severity criteria. Eligible patients were hospitalized, SARS-CoV-2 positive, had radiographic consolidations, and required supplemental oxygen but had not rapidly declined on admission or prior to drug therapy or LD-RT. Efficacy endpoints were time to clinical recovery (TTCR), radiographic improvement, and biomarker response. RESULTS: Ten patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared to ten control patients blindly matched by age and comorbidity. Six controls received COVID-19 drug therapies. Median TTCR was 12 days in the control cohort compared to 3 days in the LD-RT cohort (HR 2.9, p=0.05). Median time to hospital discharge (20 versus 12 days, p=0.19) and intubation rates (40% versus 10%, p=0.12) in the control and LD-RT cohorts were compared. Median time from admission to recovery was 10 versus 13 days (p=0.13). Hospital duration average was 19 versus 22.6 days (p=0.53). Average hospital days on supplemental oxygen of any duration was 13.1 versus 14.7 days (p=0.69). Average days with a documented fever was 1 versus 4.3 days (p=0.12). 28-day overall survival was 90% for both cohorts. The LD-RT cohort trended towards superior rates of improved radiographs (p=0.12) and delirium (p<0.01). Statistically-significant reductions were observed in numerous hematologic, cardiac, hepatic, and inflammatory markers. CONCLUSIONS: A prospective cohort of predominantly elderly hospitalized patients with COVID-19-related pneumonia were recovered to room air quicker than age- and comorbidity-matched controls, with trending or significant improvements in delirium, radiographs, and biomarkers, and no significant acute toxicity. Low dose whole-lung radiation for patients with COVID-19-related pneumonia appears safe and may be an effective immunomodulatory treatment. Larger prospective randomized trials are needed to define the efficacy of LD-RT for COVID-19.

Immunomodulatory Low-Dose Whole-Lung Radiation for Patients with COVID-19-Related Pneumonia.

To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). Inclusion criteria comprised patients with COVID-19-related moderate–severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X‑ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

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Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

Purpose The respiratory disease COVID-19 reached global pandemic status in 2020. Excessive inflammation is believed to result in the most severe symptoms and death from this disease. Because treatment options for patients with severe COVID-19 related pulmonary symptoms remain limited, whole-lung low-dose radiation therapy is being evaluated as an anti-inflammatory modality. However, there is concern about the long-term risks associated with low-dose pulmonary irradiation. To help quantify the benefit-risk balance of low-dose radiation therapy for COVID-19, we estimated radiation-induced lifetime risks of both lung cancer and heart disease (major coronary events) for patients of different sexes, treated at ages 50 to 85, with and without other relevant risk factors (cigarette smoking and baseline heart disease risk). Methods and Materials These estimates were generated by combining state-of-the-art radiation risk models for lung cancer and for heart disease together with background lung cancer and heart disease risks and age/sex-dependent survival probabilities for the U.S. population. Results Estimated absolute radiation-induced risks were generally higher for lung cancer compared with major coronary events. The highest estimated lifetime radiation-induced lung cancer risks were approximately 6% for female smokers treated between ages 50 and 60. The highest estimated radiation-induced heart disease risks were approximately 3% for males or females with high heart disease risk factors and treated between ages 50 and 60. Conclusions The estimated summed lifetime risk of lung cancer and major coronary events reached up to 9% in patients with high baseline risk factors. Predicted lung cancer and heart disease risks were lowest in older nonsmoking patients and patients with few cardiac risk factors. These long-term risk estimates, along with consideration of possible acute reactions, should be useful in assessing the benefit-risk balance for low-dose radiation therapy to treat severe COVID-19 pulmonary symptoms, and suggest that background risk factors, particularly smoking, should be taken into account in such assessments.

Lung Cancer and Heart Disease Risks Associated with Low-Dose Pulmonary Radiotherapy to COVID-19 Patients with Different Background Risks.

Recently, low dose radiotherapy delivered to the whole lung has been proposed as treatment for the pneumonia due to COVID-19. Although there is biological plausibility for its use, the evidence sup...

The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case.

This letter is a response to the letter to the editor written by Bevelacqua et al. regarding: "The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19...

Reply to: regarding: 'the risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case'.

Raissa Renata Dos Santos Weber

Papers

The risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case.

Reply to: regarding: 'the risk of induced cancer and ischemic heart disease following low dose lung irradiation for COVID-19: estimation based on a virtual case'.