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Understanding the epidemiological and clinical characteristics of fatal cases infected with SARS-CoV-2 is import to develop appropriate preventable intervention programs in hospitals. Demographic data, clinical symptoms, clinical course, co-morbidities, laboratory findings, CT scans, treatments and complications of 162 fatal cases were retrieved from electric medical records in 5 hospitals of Wuhan, China. The median age was 69.5 years old (IQR: 63.0-77.25; range: 29-96). 112 (69.1%) cases were men. Hypertension (45.1%) was the most common co-morbidity, but 59 (36.4%) cases had no co-morbidity. At admission, 131 (81.9%) cases were assessed as severe or critical. However, 39 (18.1%) were assessed as moderate. Moderate cases had a higher prevalence of hypertension and chronic lung disease comparing with severe or critical cases (P

Supplemental Digital Content is available in the text., Rationale: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55–68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57–69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19–0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15–0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12–0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. Conclusions: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

Background A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. Methods A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. Results A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57–70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5–17) days, and the duration from onset of symptoms to the study date was 31 (24–36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2–8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. Conclusions Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4

Paraquat is a quaternary nitrogen herbicide evoking mitochondrial damage and heart failure with little therapeutic remedies available. Recent reports depicted a role for unchecked autophagy in paraquat-induced cardiotoxicity. This study was designed to examine the role of the mitophagy receptor protein FUNDC1 in paraquat-induced cardiac contractile and mitochondrial injury using a murine model of FUNDC1 knockout (FUNDC1

The objective is to explore the mind map communication mode used in the emergency department combined with the SBAR standard to reduce the occurrence of handover defects and adverse events. 180 cases of emergency treatment and patient observation from January to June 2021 were selected and studied. According to the time of admission, the selected patients were divided into observation group and control group (90 cases). The control group adopts the traditional handover mode, and the observation group thinks. The map is combined with the SBAR standard communication mode to handover; compared; and observed the two groups of nurse’s handover quality scores, handover problems and adverse events, handover defects, mastery of the patient’s condition and understanding of critical illness, and nursing satisfaction. The quality scores of nurses in the control group were significantly higher than those in the observation group; the incidence of adverse events in the observation group was 8.9%, and the incidence of handover problems was 2.2%, which was significantly lower than that of the control group. The mastery score of the observation group was significantly higher than that of the control group; the nursing satisfaction of the observation group was 90% significantly higher than that of the control group. The handover defect rate of 56.7% in the control group was significantly higher than that in the observation group. The nurses in the observation group had a 98.9% understanding of the critically ill patients’ condition than in the control group. All the above items are statistically significant, P

Background: To assess the effect of methylprednisolone on the prognosis of patients with novel coronavirus pneumonia.Methods: Patients with confirmed novel coronavirus pneumonia discharged from Wuhan Third Hospital Guanggu Campus, Shouyi Campus, and Lei Shen Shan Hospital from January 31, 2020, to March 4, 2020, were included. The patients were divided into treatment and control groups according to whether methylprednisolone was used during hospitalization. Propensity score (PS) matching analysis was used to assess in-hospital mortality as the primary outcome and trends in the changes in lymphocytes and the C-reactive protein, creatinine and transaminase levels 7 days after admission (secondary outcomes).Results: A total of 2,062 patients with confirmed novel coronavirus pneumonia were included in this study. Univariate Cox regression analysis suggested that methylprednisolone treatment was associated with increased in-hospital mortality (hazard ratio (HR) 3.70, 95% confidence interval (CI) 2.62-5.23, P9/L. Kaplan-Meier survival curve analysis showed that methylprednisolone treatment reduced the risk of in-hospital death in patients with lymphocyte counts less than 0.9×109/L (P=0.022). In contrast, in the normal lymphocyte group, methylprednisolone treatment was not associated with in-hospital mortality (p=0.88).Conclusion: Treatment with methylprednisolone may be associated with reduced in-hospital mortality in coronavirus disease (COVID) patients with low lymphocyte counts.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic is a global threat caused by the severe acute respiratory syndrome coronavirus-2. AIM: To develop and validate a risk stratification tool for the early prediction of intensive care unit (ICU) admission among COVID-19 patients at hospital admission. METHODS: The training cohort included COVID-19 patients admitted to the Wuhan Third Hospital. We selected 13 of 65 baseline laboratory results to assess ICU admission risk, which were used to develop a risk prediction model with the random forest (RF) algorithm. A nomogram for the logistic regression model was built based on six selected variables. The predicted models were carefully calibrated, and the predictive performance was evaluated and compared with two previously published models. RESULTS: There were 681 and 296 patients in the training and validation cohorts, respectively. The patients in the training cohort were older than those in the validation cohort (median age: 63.0 vs 49.0 years, P < 0.001), and the percentages of male gender were similar (49.6% vs 49.3%, P = 0.958). The top predictors selected in the RF model were neutrophil-to-lymphocyte ratio, age, lactate dehydrogenase, C-reactive protein, creatinine, D-dimer, albumin, procalcitonin, glucose, platelet, total bilirubin, lactate and creatine kinase. The accuracy, sensitivity and specificity for the RF model were 91%, 88% and 93%, respectively, higher than those for the logistic regression model. The area under the receiver operating characteristic curve of our model was much better than those of two other published methods (0.90 vs 0.82 and 0.75). Model A underestimated risk of ICU admission in patients with a predicted risk less than 30%, whereas the RF risk score demonstrated excellent ability to categorize patients into different risk strata. Our predictive model provided a larger standardized net benefit across the major high-risk range compared with model A. CONCLUSION: Our model can identify ICU admission risk in COVID-19 patients at admission, who can then receive prompt care, thus improving medical resource allocation.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies.Methods: The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days).Results: A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3–27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy.Conclusions: In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.

BACKGROUND The widespread coronavirus disease 2019 (COVID-19) has led to high morbidity and mortality. Therefore, early risk identification of critically ill patients remains crucial. AIM To develop predictive rules at the time of admission to identify COVID-19 patients who might require intensive care unit (ICU) care. METHODS This retrospective study included a total of 361 patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction between January 19, 2020, and March 14, 2020 in Shenzhen Third People's Hospital. Multivariate logistic regression was applied to develop the predictive model. The performance of the predictive model was externally validated and evaluated based on a dataset involving 126 patients from the Wuhan Asia General Hospital between December 2019 and March 2020, by area under the receiver operating curve (AUROC), goodness-of-fit and the performance matrix including the sensitivity, specificity, and precision. A nomogram was also used to visualize the model. RESULTS Among the patients in the derivation and validation datasets, 38 and 9 participants (10.5% and 2.54%, respectively) developed severe COVID-19, respectively. In univariate analysis, 21 parameters such as age, sex (male), smoker, body mass index (BMI), time from onset to admission (> 5 d), asthenia, dry cough, expectoration, shortness of breath, asthenia, and Rox index < 18 (pulse oxygen saturation, SpO2)/(FiO2 × respiratory rate, RR) showed positive correlations with severe COVID-19. In multivariate logistic regression analysis, only six parameters including BMI [odds ratio (OR) 3.939; 95% confidence interval (CI): 1.409-11.015; P = 0.009], time from onset to admission (≥ 5 d) (OR 7.107; 95%CI: 1.449-34.849; P = 0.016), fever (OR 6.794; 95%CI: 1.401-32.951; P = 0.017), Charlson index (OR 2.917; 95%CI: 1.279-6.654; P = 0.011), PaO2/FiO2 ratio (OR 17.570; 95%CI: 1.117-276.383; P = 0.041), and neutrophil/lymphocyte ratio (OR 3.574; 95%CI: 1.048-12.191; P = 0.042) were found to be independent predictors of COVID-19. These factors were found to be significant risk factors for severe patients confirmed with COVID-19. The AUROC was 0.941 (95%CI: 0.901-0.981) and 0.936 (95%CI: 0.886-0.987) in both datasets. The calibration properties were good. CONCLUSION The proposed predictive model had great potential in severity prediction of COVID-19 in the ICU. It assisted the ICU clinicians in making timely decisions for the target population.

Background and aims Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. Approach and results We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. Conclusion The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.

Background The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. Methods Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. Results Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6–81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3–36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. Conclusions Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

Background:No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods:We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered withClinicalTrials.gov,NCT04257656. Findings:Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation:In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.

Background Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. Discussion This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. Trial registration ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.

Background and objectives Previous reports on the outbreak of coronavirus disease 2019 were on the basis of data from the general population. Our study aimed to investigate the clinical features of patients on maintenance hemodialysis. Design, setting, participants, & measurements In this retrospective, single-center study, we included 49 hospitalized patients on maintenance hemodialysis and 52 hospitalized patients without kidney failure (controls) with confirmed coronavirus disease 2019 at Tongren Hospital of Wuhan University from January 30, 2020 to March 10, 2020. Demographic, clinical, laboratory, and radiologic characteristics and treatment and outcomes data were analyzed. The final date of follow-up was March 19, 2020. Results The median age of 101 patients was 62 years (interquartile range, 49–72). All patients were local residents of Wuhan. In terms of common symptoms, there were differences between patients on hemodialysis and controls (fatigue [59% versus 83%], dry cough [49% versus 71%], and fever [47% versus 90%]). Lymphocyte counts were decreased (0.8×109/L [patients on hemodialysis] versus 0.9×109/L [controls], P=0.02). Comparing patients on hemodialysis with controls, creatine kinase–muscle and brain type, myoglobin, hypersensitive troponin I, B-type natriuretic peptide, and procalcitonin were increased, and the percentage of abnormalities in bilateral lung was higher in computed tomographic scan (82% versus 69%, P=0.15) and unilateral lung was lower (10% versus 27%, P=0.03). Common complications including shock, acute respiratory distress syndrome, arrhythmia, and acute cardiac injury in patients on hemodialysis were significantly higher. Compared with controls, more patients on hemodialysis received noninvasive ventilation (25% versus 6%, P=0.008). As of March 19, 2020, three patients on hemodialysis (6%) were transferred to the intensive care unit and received invasive ventilation. Seven patients on hemodialysis (14%) had died. Conclusions The main symptoms of coronavirus disease 2019 pneumonia, including fever and cough, were less common in patients on hemodialysis. Patients on hemodialysis with coronavirus disease 2019 were at higher risk of death.

Background: While 2019-nCoV nucleic acid swab tests has high false positives rate, How to diagnose 2019-nCoV pneumonia and predict prognosis by CT is very important. Methods: In this retrospective single-center study, we consecutively included suspected 2019-nCoV pneumonia critical cases in the intensive care unit of Wuhan third hospital from January 31, 2020 to February 16, 2020. The cases were confirmed by real-time RT-PCR, and all patients were evaluated with CT, cutoff values were obtained according to the Yoden index, and were divided into high CT score group and low CT score group. Epidemiological, demographic, clinical, and laboratory data were collected. Results: The major imaging feature of 2019-nCoV pneumonia is the ground glass opacity (GGO). Multivariate regression analysis found that CT score and absolute count of lymphocytes were independent risk factor for death, and CT score predicted mortality AUC-ROC =0.7, cutoff=1.45. When the absolute count of lymphocytes decreased, the patient's CT also deteriorated. Conclusion: CT score and absolute count of lymphocytes were independent risk factor for death, and patients with high CT score may have a worse prognosis. Lower absolute count of lymphocytes may indicated the patient's CT also deteriorated.

Background and purpose Chronic alcohol consumption contributes to contractile dysfunction and unfavourable geometric changes in myocardium, accompanied by altered autophagy and disturbed mitochondrial homeostasis. The E3 ubiquitin ligase Parkin encoded by PARK2 gene maintains a fundamental role in regulating mitophagy and mitochondrial homeostasis, although little is known of its role in the aetiology of alcoholic cardiomyopathy. Here we assessed the effects of Parkin deletion in chronic alcohol-evoked cardiotoxicity. Experimental approach Following alcohol (4%) or control diet intake for 8 weeks, adult male wild-type (WT) and PARK2 knockout (Parkin-/- ) mice were examined using echocardiography. Cardiomyocyte mechanical properties, morphology of myocardium, and mitochondrial damage were also evaluated. Autophagy and mitophagy levels were assessed by LC3B and GFP-LC3 puncta, and lysosome-dependent autophagic flux was scrutinized using GFP-mRFP-LC3 puncta and Bafilomycin A1 treatment. Key results Chronic alcohol exposure provoked unfavourable geometric changes in myocardium and led to mitochondrial dysfunction and cardiac contractile defects, effects further exacerbated by Parkin knockout. Chronic alcohol exposure provoked autophagy and PINK1/Parkin-mediated mitophagy without affecting lysosome-dependent autophagic flux, the effects of which were diminished by Parkin deletion. Parkin adenovirus infection in neonatal rat cardiomyocytes further increased autophagy and protected against alcohol-induced myocardial injury, effects blocked by siRNA for Ambra1 (Autophagy and Beclin1 regulator 1). Immunofluorescence staining and co-immunoprecipitation assays showed interactions between Parkin and Ambra1. Conclusions and implications Parkin was essential for cardiac homeostasis in alcohol challenge, accompanied by increased autophagy/mitophagy and maintenance of mitochondrial integrity through its interaction with Ambra1.

Background: A novel coronavirus emerged in Wuhan, Hubei Province, China towards the end of 2019 (SARS-CoV-2 or COVID-19 virus). Large scale spread within China and internationally led the World Health Organisation to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including highkly pathogenic MERS-CoV and SARS-CoV, in in-vitro and in-vivo experiments. It is also inhibitory against COVID-19 virus in-vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe pneumonia caused by COVID-19 virus infection.Methods: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥18 years) with laboratory confirmed COVID-19 virus infection, and severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenous remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death). One interim analysis for efficacy and futility will be conducted once half of the total number of events required had been observed.Discussion: This is the first randomized, placebo-controlled trial in 2019-nCoV. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020.

Background: Considering the current situation of the novel coronavirus disease (COVID-19) epidemic control, it is highly likely that COVID-19 and influenza may coincide during the approaching winter season. However, there is no available tool that can rapidly and precisely distinguish between these two diseases in the absence of laboratory evidence of specific pathogens. Methods: Laboratory confirmed COVID-19 and influenza patients from Zhongnan Hospital of Wuhan University (ZHWU) and Wuhan No.1 Hospital (WNH) between December 1, 2019 and February 29, 2020, were included for analysis. A machine learning-based decision model was developed using the XGBoost algorithms. The specificity, sensitivity, positive and negative predictive values (PPV/NPV), accuracy and area under the receiver operating characteristic curve (AUC) were calculated to evaluate the model performance. Findings: The data from 357 COVID-19 and 1893 influenza patients from ZHWU were divided into a training and a testing set in the ratio 7:3. The external test used the data of 308 COVID-19 and 312 influenza patients from WNH. In the training and testing sets, the model achieved good performance in identifying COVID-19 from influenza with an accuracy of 0.968 (AUC, 0.943 (95%CI 0.925, 0.962)) and 0.960 (AUC, 0.928 (95%CI 0.897, 0.959)), respectively. Our decision tree suggested that older age (>16 years), higher hsCRP (>14.2 mg/L) and lower monocyte (≤0.68×109/L) drive the prediction towards COVID-19. In addition, the external test determined a COVID-19 prediction accuracy of 0.839 (AUC, 0.839 (95%CI: 0.811, 0.868). Interpretation: Machine learning provides a tool that can rapidly and accurately distinguish between COVID-19 and influenza cases. This finding would be particularly useful in regions having massive COVID-19 and influenza cases while limited resources for laboratory test of specific pathogens. Funding: National Natural Science Foundation of China (81900097) and the Emergency Response Project of Hubei Science and Technology Department (2020FCA002, 2020FCA023). Declaration of Interests: None reported. Ethics Approval Statement: This study was approved by the Medical Ethics Committee, Zhongnan Hospital of Wuhan University (Clinical Ethical Approval No. 2020020).

Additional file 1: S1. Symptoms of 239 critically ill patients with COVID-19.

Background: Influenza co-circulates with coronavirus disease 2019 (COVID-19) in the space and time Given the current situation of COVID-19 pandemic and influen

Parkinson's disease is a degenerative central nervous system disorder that often impairs motor skills, speech and other functions. We discovered a large Chinese family showing primarily parkinsonism symptoms with autosomal dominant inheritance. Six affected individuals in the family showed typical parkinsonism symptoms, including pill-rolling tremor. Two other affected individuals showed cerebellar ataxia symptoms. A whole-genome scan using the 50K single nucleotide polymorphism array with three different linkage methods detected two positive regions on chromosome 12q24.1 and 5q13.3. The ATXN2 gene, responsible for spinocerebellar ataxia type 2 (SCA2) was located precisely in the center of the positive region on chromosome 12. Further analysis of SCA2 revealed heterozygous pathological CAG expansions in the family. The affected individuals' symptoms were typical of parkinsonism, but complex. Inverse correlation between CAG repeat size and age of onset is not obvious in this pedigree. This parkinsonism-predominant SCA2 family shared the same disease gene locus with other 'standard' SCA2 families, but it is possible that variations in one or more modifier genes might account for the parkinsonism-predominant SCA2 predisposition observed in this pedigree.