Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

Acute phase characteristics and long-term complications of pulmonary embolism in COVID-19 compared to non-COVID-19 cohort: a large single-centre study.

BACKGROUND: To compare the severity of pulmonary embolism (PE) and the long-term complications between patients with and without COVID-19, and to investigate whether the tools for risk stratification of death are valid in this population. METHODS: We retrospectively included hospitalized patients with PE from 1 January 2016 to 31 December 2022. Comparisons for acute episode characteristics, risk stratification of the PE, outcomes, and long-term complications were made between COVID and non-COVID patients. RESULTS: We analyzed 116 (27.5%) COVID patients and 305 (72.4%) non-COVID patients. In patients with COVID-19, the traditional risk factors for PE were absent, and the incidence of deep vein thrombosis was lower. COVID patients showed significantly higher lymphocyte count, lactate dehydrogenase, lactic acid, and D-dimer levels. COVID patients had PE of smaller size (12.3% vs. 25.5% main pulmonary artery, 29.8% vs. 37.1% lobar, 44.7% vs. 29.5% segmental and 13.2% vs. 7.9% subsegmental, respectively; p < 0.001), less right ventricular dysfunction (7.7% vs. 17.7%; p = 0.007) and higher sPESI score (1.66 vs. 1.11; p < 0.001). The need for mechanical ventilation was significantly higher in COVID patients (8.6% vs. 1.3%; p < 0.001); However, the in-hospital death was less (5.2% vs. 10.8%; p = 0.074). The incidence of long-term complications was lower in COVID cohort (p < 0.001). PE severity assessed by high sPESI and intermediate and high-risk categories were independently associated with in-hospital mortality in COVID patients. CONCLUSION: The risk of in-hospital mortality and the incidence of long-term complications were lower in COVID-19. The usual tools for risk stratification of PE are valid in COVID patients.

[Post-COVID-19 severe cholangiopathy: report of 6 cases]

Coronavirus disease 2019 (COVID-19) is a predominantly respiratory tract infection with the capacity to affect other organs. Liver chemistry abnormalities are a frequent manifestation of COVID-19 but are usually transient. We describe the clinical course and most relevant findings of 6 patients who developed a cholangiopathy after severe COVID-19. The mean age of the patients, 4 men and 2 women, was 56 years and the mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 138 days. The features most important were the increase of alkaline phosphatase and destructuring and beading of the intrahepatic bile duct in magnetic resonance imaging. Cholangiopathy after severe COVID-19 constitutes a novel entity with unique features and potential for progressive biliary injury and secondary biliary cirrhosis. Further studies are required to understand this disease.

Male sex is associated with in-hospital death in non-dialysis CKD patients with COVID-19

BACKGROUND AND AIMS: Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) can lead to significant organ injury. CKD has been associated with increased mortality in previous epidemics, and male sex has been correlated with worse outcomes during COVID-19 in the general population. Our aim was to describe the differential effect of sex as a risk factor for in-hospital mortality among non-dialysis CKD subjects. METHOD: Multicenter, observational cohort study including 136 adult patients with CKD and 136 age- and sex-matched controls who required admission for COVID-19 in three academic hospitals in Spain. Viral infection was confirmed by real-time RTqPCR and/or serologic testing in all cases. Disease severity on admission was classified according to the WHO-China Joint Mission Report on COVID-19. The presence of CKD was defined as sustained eGFR <60 and >15 ml/min/1.73m2 within the 6 months prior to COVID-19 hospitalization. Demographic and clinical data were gathered from medical records. Outcomes were recorded during the following 28 days after admission. We applied Cox proportional hazards models, adjusted for age, sex, hypertension, diabetes and severe or critical disease at presentation. RESULTS: Due to the matched design, no differences were found regarding age and sex between cohorts. CKD patients suffered more frequently from hypertension and diabetes and presented higher 28-day mortality after hospital admission due to COVID-19 compared with age- and sex-matched controls (40.4 vs. 24.3%;P=0.004). In adjusted Cox regression analysis among CKD patients, only age (HR: 1.087, 95% CI: 1.047-1.128) and male sex (HR: 1.883, 95% CI: 1.045-3.391) were independent predictors of 28-day mortality. Comparatively, among patients without CKD, only age acted as an independent predictor for 28-day mortality (HR: 1.082, 95% CI: 1.033- 1.133). None of the variables included in adjusted regression was able to predict ICU admission in any of the cohorts. CONCLUSION: Male sex is associated with increased mortality, but not with ICU admission, after hospitalization due to COVID-19 among non-dialysis CKD patients. That effect was not observed among hospitalized controls without CKD.

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: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: 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. RESULTS: 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 X­ray. 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. CONCLUSIONS: 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.

Saving time in the radiotherapy procedures for COVID-19 pneumonia treatment. A single-institution experience.

BACKGROUND: The use of low dose radiotherapy (LD-RT) for the treatment of COVID-19 pneumonia is supported by biological rationale for its immunomodulatory effect. Some institutions have started to treat these patients showing encouraging results. To shorten procedure times is crucial for the comfort of symptomatic patients receiving respiratory support and to optimize institutional facilities. PATIENTS AND METHODS: At our institution, LD-RT is offered to hospitalized patients with COVID-19 pneumonia and signs of early cytokine-released syndrome on behalf of a multicenter study. We designed a coordinated process flow starting from the patient transfer to the simulation CT-scan (first-step), to the end of the LD-RT treatment (last step). The times spent on each step of the process flow were evaluated. RESULTS: Mean age of treated patients was 83 (72-91) years-old. The timing parameters of the first 10 consecutive patients were analyzed. Except for the first (dummy run), patients were managed from the first to the last step in a median of 38 min (25-58, SD 10.67). The most time-consuming sub-process was the contouring of the treatment volumes and dosimetry. CONCLUSIONS: LD-RT is not only an encouraging option for COVID-19 pneumonia patients, but a convenient and feasible procedure if performed in a coordinated way by reducing procedure times.

Alopecia and severity of COVID-19: a cross-sectional study in Peru

The aim of this study was to determine the relationship between COVID-19 severity and androgenic alopecia in patients hospitalized in the Surgery Service of Honorio Delgado Espinoza Hospital in Arequipa, Peru. A cross-sectional study was performed in male patients with a diagnosis of COVID-19. Alopecia, clinical characteristics, treatment, and evolution were collected. In all, 98 patients were included;median age was 55 years old (range 18-89), 32.7% with comorbidities, and 45.9% with androgenic alopecia. The severity of COVID-19 infection was moderate to severe in 13.2% of patients without alopecia, and in 88.9% of patients with alopecia (p>0.001). In the logistic regression model analysis, patients with alopecia had a higher risk of presenting moderate to severe symptoms due to SARS-CoV-2 infection (OR: 80.2;95% CI 16.2-397.7). In conclusion, the severity of infection was statistically significant in patients over 60 years old and those with alopecia.

Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial.

BACKGROUND: COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. STUDY DESIGN AND METHODS: This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.