Effectiveness of Regdanvimab in Patients With Mild-to-moderate COVID-19: A Retrospective Cohort Study

BackgroundMonoclonal antibodies are a treatment option for patients with mild-to-moderate coronavirus disease (COVID-19). We investigated the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody approved in South Korea, in the treatment of patients with mild-to-moderate COVID-19. MethodsMedical records of mild-to-moderate COVID-19 patients admitted to a COVID-19 designated hospital were reviewed to assess baseline characteristics (age, gender, BMI, and comorbidities) and clinical outcomes such as supplemental oxygen requirements, mortality, and length of hospitalization.ResultsFour hundred seventy-four COVID-19 patients were included in the study, and 66 of them were administered regdanvimab. The proportion of patients requiring supplemental oxygen was significantly lower in the regdanvimab group than in control group without statistical significance (6.1% vs. 22.8%, P = 0.001). There was no significant difference in mortality (0% vs 1.2%, P > 0.999) and the length of hospitalization (median: 10.5 days vs. 7.5 days, P = 0.067) between both groups. Increasing age, male sex, chest X-ray abnormality, underlying chronic kidney disease and administration of regdanvimab were found to have a significant univariate association with oxygen requirement. The multivariate analysis demonstrated that increasing age (OR: 1.03, 95% CI: 1.01-1.05, P < 0.001) and chest X-ray abnormality (OR: 4.40, 95% CI: 2.49-8.21, P < 0.001) were independently associated with higher requirement of oxygen and administration of regdanvimab was independently associated with lower oxygen supplement (OR: 0.17, 95% CI: 0.05-0.47, P < 0.002). ConclusionsRegdanvimab reduced the need for supplemental oxygen and fatalities in mild-to-moderate COVID-19 patients who matching the indications for administration of regdanvimab.

220 Electrocardiographic findings and mortality in COVID-19 patients hospitalized in different clinical settings

Aims 12-lead electrocardiogram (ECG) still represents the first line approach for cardiovascular assessment even in patients with COVID-19. We therefore sought to describe and compare ECG findings in three different hospital settings: intensive care unit (ICU) (invasive ventilatory support), respiratory care unit (RCU) (non-invasive ventilatory support) and Covid-19 dedicated internal medicine unit (IMU) (oxygen supplement with or without high flow). Methods and results We retrospectively analysed the 12-lead ECGs of 1124 consecutive patients hospitalized for respiratory distress and COVID-19 in a single III level hospital. Age, gender, main clinical data and in-hospital survival were recorded. 548 patients were hospitalized in IMU, 361 in RCU, 215 in ICU. Arrhythmias in general were less frequently found in RCU (16% vs. 26%, P &lt; 0.001). Deaths occurred more frequently in ICU patients (43% vs. 20–21%, P &lt; 0.001). After pooling predictors of mortality (age, intensity of care setting, heart rate, ST-elevation, QTc prolongation, Q-waves, right bundle branch block, and atrial fibrillation), the risk of in-hospital death can be estimated by using a derived score. Three zones of mortality risk can be thus identified: &lt;5%, score &lt;5 points; 5–50% score 5–10, and &gt;50%, score &gt;10 points. The accuracy of the score assessed at ROC curve analysis was 0.791. Conclusions ECG differences at admission con be found in COVID-19 patients according to different clinical settings and intensity of care. A simplified score derived from few clinical and ECG variables may predict in-hospital mortality with a good accuracy.

Effectiveness of Chest Physiotherapy on Cardio-Respiratory Signs & Symptoms in COVID-19 Positive Patients

Introduction: Covid-19 is considered as world pandemic disease in which patient suffers from several respiratory impairments along with weakness which affects overall body functions, thus aim of this review is to highlight role of chest physiotherapy in improving respiratory signs/symptoms of Covid-19 positive patients. Method: The interventional study, convenient sampling with sample size of 41 subjects. Subjects of 35-80 years both male and female diagnosed with covid-19 positive were included in study. The exclusion criteria were any recent fracture, any medically diagnosed mental illness, neurological disorders and post covid-19 patients. The subjects are assessed of respiratory signs and symptoms like vital-signs, cough, dyspnea by American thoracic society grading of breathlessness, 1 minute sit to stand test, external oxygen supplement on the 1st day and again on 14th day physiotherapy administration for data analysis. The symptomatic chest physiotherapy was administered to each patient from day of reference until the discharge, 2 times in a day and 7 days/week. Results: There was decrease in mean ATS dyspnea scoring, respiratory rate, cough and oxygen supplement and increase in mean 1 minute sit to stand repetition, oxygen saturation (spo2) from 1st day to 14th day of physiotherapy treatment which is statistically significant comparing within groups. There was no significant difference noted in pre and post heart rate values comparing within groups. Conclusion: The study concluded that chest physiotherapy proved to be effective in improving the respiratory signs and symptoms and overall health of covid-19 positive patients. Key words: Covid-19 positive, chest physiotherapy, cough, dyspnea, oxygen supplement.

COVID-19 Outcome Prediction and Monitoring Solution for Military Hospitals in South Korea: Development and Evaluation of an Application

Background COVID-19 has officially been declared as a pandemic, and the spread of the virus is placing sustained demands on public health systems. There are speculations that the COVID-19 mortality differences between regions are due to the disparities in the availability of medical resources. Therefore, the selection of patients for diagnosis and treatment is essential in this situation. Military personnel are especially at risk for infectious diseases; thus, patient selection with an evidence-based prognostic model is critical for them. Objective This study aims to assess the usability of a novel platform used in the military hospitals in Korea to gather data and deploy patient selection solutions for COVID-19. Methods The platform’s structure was developed to provide users with prediction results and to use the data to enhance the prediction models. Two applications were developed: a patient’s application and a physician’s application. The primary outcome was requiring an oxygen supplement. The outcome prediction model was developed with patients from four centers. A Cox proportional hazards model was developed. The outcome of the model for the patient’s application was the length of time from the date of hospitalization to the date of the first oxygen supplement use. The demographic characteristics, past history, patient symptoms, social history, and body temperature were considered as risk factors. A usability study with the Post-Study System Usability Questionnaire (PSSUQ) was conducted on the physician’s application on 50 physicians. Results The patient’s application and physician’s application were deployed on the web for wider availability. A total of 246 patients from four centers were used to develop the outcome prediction model. A small percentage (n=18, 7.32%) of the patients needed professional care. The variables included in the developed prediction model were age; body temperature; predisease physical status; history of cardiovascular disease; hypertension; visit to a region with an outbreak; and symptoms of chills, feverishness, dyspnea, and lethargy. The overall C statistic was 0.963 (95% CI 0.936-0.99), and the time-dependent area under the receiver operating characteristic curve ranged from 0.976 at day 3 to 0.979 at day 9. The usability of the physician’s application was good, with an overall average of the responses to the PSSUQ being 2.2 (SD 1.1). Conclusions The platform introduced in this study enables evidence-based patient selection in an effortless and timely manner, which is critical in the military. With a well-designed user experience and an accurate prediction model, this platform may help save lives and contain the spread of the novel virus, COVID-19.

HFD and HFD-provoked hepatic hypoxia act as reciprocal causation for NAFLD via HIF-independent signaling

Background The occurrence of non-alcoholic fatty liver disease (NAFLD) is found to be higher in patients with obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia. Activation of hypoxia-inducible factors has been shown in the development and progression of NAFLD, implying a cause and effects relationship between NAFLD and hypoxia. The present study was designed to investigate the interaction of lipotoxicity and hypoxia in the pathogenesis of NAFLD using mice model with high-fat diet (HFD) feeding or hypoxic treatment. Methods NAFLD model was induced in mice by HFD feeding, and in cultured primary hepatocytes by administration of palmitate acid. Mouse hypoxic model was produced by placing the mice in a Animal incubator with oxygen concentration at 75% followed by a 21% oxygen supplement. Hypoxic condition was mimicked by treating the hepatocytes with cobalt chloride (CoCl2) or 1% oxygen supply. Pimonidazole assay was conducted to evaluate hypoxia. Lipid metabolic genes were measured by real-time polymerase-chain reaction. HIF-1α and HIF-2α genes were silenced by siRNA. Results HFD feeding and palmitate acid treatment provoked severe hepatic hypoxia along with TG accumulation in mice and in cultured primary hepatocytes respectively. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured primary hepatocytes. Hypoxic treatment inhibited the expression of lipolytic genes, while increased the expression of lipogenicgenes in mice. Although both lipotoxicity and hypoxia could activate hepatic hypoxia-induced factor 1α and 2α, while neither lipotoxicity- nor hypoxia- induced hepatic steatosis was affected when HIF was knocked down. Conclusions HFD resulted in hepatic TG accumulation and concomitant hypoxia. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured heptocytes. Thus lipotoxicity and hypoxia might work as reciprocal causation and orchestrate to promote the development of NAFLD.

Comparative Study on the Effect of Cidofovir Treatment for Severe Adenovirus Pneumonia

Background: Adenovirus infection can cause severe pneumonia even in immunocompetent adults. However, there is limited data on the benefits of cidofovir treatment in severe adenovirus pneumonia. The objective of this study was to evaluate the association of cidofovir treatment with clinical improvement in immunocompetent adult patients with severe adenovirus pneumonia. Methods: We evaluated 22 male patients who admitted to intensive care unit (ICU) with severe adenovirus pneumonia between January 2014 and December 2019. The patients were divided into 2 groups, patients treated with cidofovir or not. Clinical outcomes including time to defervescence and stopping of oxygen supplement, length of stay in ICU and hospital, and the need for mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) were compared between the 2 groups. Results: Among 22 patients, 13 patients (59%) were treated with cidofovir and 9 (41%) were not. The difference in mean time (95% confidence interval [CI]) to defervescence and stopping of oxygen supplement between cidofovir group and no cidofovir group was 2.1 (−5.7 to 10.0) and 1.0 (−14.9 to 16.8) days, respectively. The difference in mean length of stay (95% CI) in ICU and hospital between the 2 groups was 0.2 (−7.1 to 7.5) and −0.4 (−18.3 to 17.5) days, respectively. The differences in proportion of patients requiring MV and ECMO between the 2 groups was 28.2 (−17.4 to 73.8) % and −10.3 (−52.2 to 31.7) %, respectively. Conclusions: The treatment with cidofovir for severe adenovirus pneumonia in immunocompetent patients did not improve clinical outcomes. Further studies with larger samples with prospective design are warranted.

COVID-19 Outcome Prediction and Monitoring Solution for Military Hospitals in South Korea: Development and Evaluation of an Application (Preprint)

BACKGROUND COVID-19 has officially been declared as a pandemic, and the spread of the virus is placing sustained demands on public health systems. There are speculations that the COVID-19 mortality differences between regions are due to the disparities in the availability of medical resources. Therefore, the selection of patients for diagnosis and treatment is essential in this situation. Military personnel are especially at risk for infectious diseases; thus, patient selection with an evidence-based prognostic model is critical for them. OBJECTIVE This study aims to assess the usability of a novel platform used in the military hospitals in Korea to gather data and deploy patient selection solutions for COVID-19. METHODS The platform’s structure was developed to provide users with prediction results and to use the data to enhance the prediction models. Two applications were developed: a patient’s application and a physician’s application. The primary outcome was requiring an oxygen supplement. The outcome prediction model was developed with patients from four centers. A Cox proportional hazards model was developed. The outcome of the model for the patient’s application was the length of time from the date of hospitalization to the date of the first oxygen supplement use. The demographic characteristics, past history, patient symptoms, social history, and body temperature were considered as risk factors. A usability study with the Post-Study System Usability Questionnaire (PSSUQ) was conducted on the physician’s application on 50 physicians. RESULTS The patient’s application and physician’s application were deployed on the web for wider availability. A total of 246 patients from four centers were used to develop the outcome prediction model. A small percentage (n=18, 7.32%) of the patients needed professional care. The variables included in the developed prediction model were age; body temperature; predisease physical status; history of cardiovascular disease; hypertension; visit to a region with an outbreak; and symptoms of chills, feverishness, dyspnea, and lethargy. The overall C statistic was 0.963 (95% CI 0.936-0.99), and the time-dependent area under the receiver operating characteristic curve ranged from 0.976 at day 3 to 0.979 at day 9. The usability of the physician’s application was good, with an overall average of the responses to the PSSUQ being 2.2 (SD 1.1). CONCLUSIONS The platform introduced in this study enables evidence-based patient selection in an effortless and timely manner, which is critical in the military. With a well-designed user experience and an accurate prediction model, this platform may help save lives and contain the spread of the novel virus, COVID-19.

Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study

While the recent study on the compassionate use of remdesivir for COVID-19 patients has shown a 68% clinical improvement7 it is a one-arm study that renders the evaluation of the efficacy in reducing death and the length of stay of hospitalization intractable due to a lacking of the control group. We came up with a two-arm controlled study design to simulate the treated and the untreated (control group) group by applying two respective transition models to the empirical data on dynamics of the disease severity (Figure 2 of the original article7) that are classified into low- (no and low oxygen supplement), medium- (non-invasive ventilator and high oxygen supplement), and high-(ECMO and invasive ventilator) from enrolment until discharge, death or the end of follow-up. By using a simulated two-arm controlled study, the remdesivir treatment group as opposed to the control group led to a statistically significantly 29% (95% CI: 22-35%) reduction of death from COVID-19. The treated group also revealed a 33% (95% CI 28-38%) significantly higher odds of discharge than the control group. The median time to discharge for the treated group (5.5 days, 16.5 days, and 29.5 days for low-, medium-, and high-risk state, respectively) was around half of those of the control arm. Our results with a simulated two-arm controlled study have not only corroborated the efficacy of remdesivir but also made great contribution to designing a further large-scale randomized controlled trial. They have significant implications for reducing transmission probability and infectious time of COVID-19 patients when contacting with susceptible health care workers during hospitalization.Key PointsQuestionWhat is the efficacy of remdesivir in reducing advanced disease state or death from COVID-19 and the length of stay of hospitalization?FindingsRemdesivir treatment results in a 33% significantly higher odds of discharge, a 29% significantly lower risk of death, and a 39% significantly lower risk for the combined endpoint of severe status and death. The median time to discharge for the remdesivir treated group was around half of the median time-to-discharge compared with the control arm.MeaningRemdesivir is effective in treating COVID-19 patients in terms of enhancing recovery and accelerating discharge.

Design of a Sandwich Hierarchically Porous Membrane with Oxygen Supplement Function for Implantable Glucose Sensor

This study aims to develop an oxygen regeneration layer sandwiched between multiple porous polyurethanes (PU) to improve the performance of implantable glucose sensors. Sensors were prepared by coating electrodes with platinum nanoparticles, Nafion, glucose oxidase and sandwich hierarchically porous membrane with an oxygen supplement function (SHPM-OS). The SHPM-OS consisted of a hierarchically porous structure synthesized by polyethylene glycol and PU and a catalase (Cat) layer that was coated between hierarchical membranes and used to balance the sensitivity and linearity of glucose sensors, as well as reduce the influence of oxygen deficiency during monitoring. Compared with the sensitivity and linearity of traditional non-porous (NO-P) sensors (35.95 nA/mM, 0.9987, respectively) and single porous (SGL-P) sensors (45.3 nA /mM, 0.9610, respectively), the sensitivity and linearity of the SHPM-OS sensor was 98.45 nA/mM and 0.9989, respectively, which was more sensitive with higher linearity. The sensor showed a response speed of five seconds and a relative sensitivity of 90% in the first 10 days and remained 78% on day 20. This sensor coated with SHPM-OS achieved rapid responses to changes of glucose concentration while maintaining high linearity for long monitoring times. Thus, it may reduce the difficulty of back-end hardware module development and assist with effective glucose self-management for people with diabetes.