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Background Persistent immunosuppression characterized by immune cells apoptosis and T- lymphocyte subsets imbalance, occurs in septic patients with poor outcomes. Recent studies reported that Esmolol improved survival in septic shock via modulating immune responses. We hypothesized Esmolol alleviate sepsis-induced immunosuppression by regulating immune cell apoptosis and differentiation and sought to investigate the potential mechanisms and optimal dose. Methods Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (Esmolol:5mg.kg− 1.h− 1) and CLP + E-18 (Esmolol:18mg.kg− 1.h− 1) group. Another 8 rats were under sham operation. 18 hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and circulating T-lymphocyte subsets counts were determined by flow cytometry, protein expressions of p-Akt, Bcl-2, cleaved Caspase-3 and p-Erk1/2 were determined by western blot and immunohistochemistry. mRNA and protein expressions of β1-adrenoreceptors were evaluated by quantitative real-time PCR and immunohistochemistry. Results CLP induced tachycardia, hypotension, hyperlactatemia and multiple organ injuries. Infusion of Esmolol at 5mg.kg− 1.h− 1 didn't reduce heart rate, but improved mean arterial pressure, lactatemia and multiple organ injuries, decreased circulating T-lymphocyte apoptosis and the ratio of T help 2 cells and T help 1 cells, unregulated p-Akt and Bcl-2 expression and down-regulated cleaved Caspase-3 and p-Erk1/2 expression. Conclusions Esmolol without heart rate reduction attenuated sepsis-induced immunosuppression by preventing T-lymphocytes from apoptosis through regulating Akt/Bcl-2/Caspase-3 pathway and reducing naive CD4+ T cells differentiation to T help 2 cell through inhibiting Erk1/2 activation. Esmolol may be a potential immune regulator in septic shock.

Interstitial lung disease (ILD) is a frequent extra-articular manifestation of rheumatoid arthritis (RA) and increases mortality in patients with RA. Early identification of ILD, especially the usual interstitial pneumonia (UIP) pattern with a poor prognosis, is important for guiding treatment of RA-ILD and preventing damage resulting from a delay in diagnosis. Interleukin-36 (IL-36) cytokines are involved in connective tissue diseases. However, IL-36 expression in RA-ILD is unknown. In this study, the clinical relevance of plasma IL-36 cytokines was evaluated in 39 patients with RA-ILD and three other groups (30 healthy controls [HCs], 35 RA patients without ILD, and 27 patients with idiopathic pulmonary fibrosis [IPF]) in the Chinese population. Plasma IL-36α and IL-36γ concentrations were elevated in patients with RA-ILD compared with those in HCs and patients with RA. RA-ILD patients with UIP pattern had higher plasma IL-36γ concentrations than those with RA-ILD without UIP, but these were lower than those in patients with IPF. Receiver operating curve analysis suggested that IL-36α and IL-36γ were potential biomarkers for identifying ILD in patients with RA. Additionally, the optimal cutoff value of IL-36γ for distinguishing RA-ILD with the UIP pattern from RA-ILD without UIP was 555.40 pg/mL and that for distinguishing RA-ILD from IPF was 655.10 pg/mL. No significant difference in plasma IL-36β or IL-36Ra concentrations was found between patients with RA-ILD and the three other groups. We also found that the lungs originating from different types of patients with PF, including RA-ILD and IPF, and those from mice following bleomycin-induced PF were characterized by increased IL-36γ expression. Our findings suggest that using IL-36 cytokines to identify patients with RA for further ILD workups may provide additional diagnostic value to the current clinically available assays. Moreover, IL-36γ may help to identify the presence of the UIP pattern in patients with RA-ILD and to discriminate RA-ILD from IPF.

[Background] Co-infection of multiple pathogens into one host is a great threat to public health, for it exacerbates symptoms and leads to worse outcomes compared to single pathogen infection. Both Mycobacterium tuberculosis (Mtb) and microsporidia are wide spread pathogens world-widely. However, the co-infection of Mycobacterium tuberculosis with microsporidia has long been underestimated. [Methods] Current study recruited Mtb-positive pulmonary patients and Mtb-negative patients yet immune-suppressed due to various causes. Stool samples were collected from these two groups of individuals and the total DNAs were isolated. Quantitative PCR (qPCR) assay was used to detect the presence of microsporidia in these samples. [Results] The results showed that infection rates of microsporidia are 39.6% (23/58) in Mtb-positive group and 50% (4/8) in Mtb-negative yet immune-suppressed group. Sequencing of the positive further revealed that the infected microsporidia species include all four common human-infecting microsporidia which are Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon cuniculi and Encephalitozoon hellem. [Conclusion] Our report is the first to investigate and compare the influences of Mtb-infection and host immune state in microsporidia infection. Our findings demonstrated that microsporidia have high co-infection incidence with Mtb, and the host immune state has profound influence on infection of microsporidia. [Trial Registration] N/A.

Objectives The outbreak of the 2019 coronavirus disease (COVID-19) pandemic in Wuhan, China, has subsided after being hard hit by the disease and subsequent city lockdown. Information on the number of people involved in Wuhan is still inadequate. This study aimed to describe the screening results of 61 437 community members in Wuchang District, Wuhan. Methods In mid-May 2020, Wuhan launched a population-scale city-wide SARS-CoV-2 testing campaign, which aimed to perform nucleic acid and viral antibody testing for citizens in Wuhan. Here we show the screening results of cluster sampling of 61 437 residents in Wuchang District, Wuhan, China. Results A total of 1470 (2.39%, 95% CI 2.27–2.52) individuals were detected positive for at least one antiviral antibody. Among the positive individuals, 324 (0.53%, 95% CI 0.47–0.59) and 1200 (1.95%, 95% CI 1.85–2.07) were positive for immunoglobulin IgM and IgG, respectively, and 54 (0.08%, 95% CI 0.07–0.12) were positive for both antibodies. The positive rate of female carriers of antibodies was higher than those of male counterparts (male-to-female ratio of 0.75), especially in elderly citizens (ratio of 0.18 in 90+ age subgroup), indicating a sexual discrepancy in seroprevalence. In addition, viral nucleic acid detection using real-time PCR had showed 8 (0.013%, 95% CI 0.006–0.026) asymptomatic virus carriers. Discussion The seroprevalence of SARS-CoV-2 in Wuhan was low. Most Wuhan residents are still susceptible to this virus. Precautions, such as wearing mask, frequent hand hygiene and proper social distance, are necessary before an effective vaccine or antiviral treatments are available.

The poor outcomes in advanced non-small-cell lung cancer (NSCLC) necessitate new treatments. Recent studies emphasize anisomycin as a promising anti-cancer drug candidate. In this work, we systematically investigated the efficacy of anisomycin alone and its combination with the standard-of-care drugs in NSCLC. We showed that anisomycin inhibited growth, migration, and survival in NSCLC cells regardless of genetic mutation status, and to a greater extent than in normal lung epithelial cells. Isobologram analysis showed that the combination of anisomycin with cisplatin, paclitaxel, or gefitinib was synergistic in NSCLC but not normal lung cells. We further demonstrated that anisomycin inhibited NSCLC growth in mice. The combination of anisomycin with cisplatin was more effective than cisplatin alone and completely arrested NSCLC growth throughout the whole duration of treatment. JNK and p38 MAPK were not required for anisomycin's action. In contrast, anisomycin inhibits PI3K/Akt/mTOR pathway. Overexpression of constitutively active Akt reversed the pro-apoptotic effect of anisomycin. Our work demonstrates the selective anti-NSCLC activity of anisomycin via suppressing PI3K/Akt/mTOR. Our findings provide preclinical evidence to initialize the clinical trial of using anisomycin to sensitize NSCLC to current therapy.

Summary Background Globally, there have been many cases of coronavirus disease 2019 (COVID-19) among medical staff; however, the main factors associated with the infection are not well understood. Aim To identify the super-factors causing COVID-19 infection in medical staff in China. Methods A cross-sectional study was conducted between January 1st and February 30th, 2020, in which front-line members of medical staff who took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. Findings A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree: 572; closeness: 25; betweenness centrality: 3.23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree: 370; closeness: 29; betweenness centrality: 0.37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree: 201; closeness: 28; betweenness centrality: 5.64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. Conclusion High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor contributing to COVID-19 infections among medical staff was touching the cheek, nose, and mouth while working.

Although the introduction of immune- and targeted-therapy has improved the clinical response and outcomes, lung cancer remains a therapeutic challenge. Developing new therapeutics is necessary to improve the treatment of lung cancer. Here, we show that ribavirin, a clinically available anti-viral drug, is an attractive candidate for lung cancer treatment. We show that ribavirin is active against a panel of lung cancer cell lines regardless of molecular and cellular heterogeneity. Notably, the effective concentrations of ribavirin are clinically achievable, display minimal toxicity to normal cells and synergistic effect with paclitaxel. Its potent efficacy and synergism with chemotherapy on cancer cell, and minimal toxicity on normal cells are observed in lung xenograft mouse model. Ribavirin is also an angiogenesis inhibitor as it inhibits capillary network formation, growth and survival of human lung tumor-associated endothelial cell (HLT-EC). The mechanism studies demonstrate that ribavirin acts on lung cancer cells via suppressing eIF4E and mTOR signaling, leading to the subsequent inhibition of eIF4E-mediated protein translation. Our work suggests that ribavirin has advantage than many anti-cancer agents by targeting both tumor cells and angiogenesis. Our work also highlights the therapeutic potential of ribavirin for the treatment of lung cancer.

Cross-sectional studies are observational studies that analyze data from a population at a single point in time. They are often used to measure the prevalence of health outcomes, understand determinants of health, and describe features of a population. Unlike other types of observational studies, cross-sectional studies do not follow individuals up over time. They are usually inexpensive and easy to conduct. They are useful for establishing preliminary evidence in planning a future advanced study. This article reviews the essential characteristics, describes strengths and weaknesses, discusses methodological issues, and gives our recommendations on design and statistical analysis for cross-sectional studies in pulmonary and critical care medicine. A list of considerations for reviewers is also provided.

Introduction: Severe acute respiratory viral infections are frequency accompanied by multiple organ dysfunction, including acute kidney injury (AKI). In December 2019, the coronavirus disease 2019 (COVID-19) outbreak began in Wuhan, Hubei Province, China, and rapidly spread worldwide. While diffuse alveolar damage and acute respiratory failure are the main features of COVID-19, other organs may be involved, and the incidence of AKI is not well described. We assessed the incidence and clinical characteristics of AKI in patients with laboratory-confirmed COVID-19 and its effects on clinical outcomes. Methods: We conducted a multicenter, retrospective, observational study of patients with COVID-19 admitted to two general hospitals in Wuhan from 5 January 2020 to 21 March 2020. Demographic data and information on organ dysfunction were collected daily. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 72 h after admission or after 72 h, respectively. Results: Of the 116 patients, AKI developed in 21 (18.1%) patients. Among them, early and late AKI were found in 13 (11.2%) and 8 (6.9%) patients, respectively. Compared with patients without AKI, patients with AKI had more severe organ dysfunction, as indicated by a higher level of disease severity status, higher sequential organ failure assessment (SOFA) score on admission, an increased prevalence of shock, and a higher level of respiratory support. Patients with AKI had a higher SOFA score on admission (4.5 ± 2.1 vs. 2.8 ± 1.4, OR 1.498, 95% CI 1.047–2.143 ) and greater hospital mortality (57.1% vs. 12.6%, OR 3.998, 95% CI 1.088–14.613) than patients without AKI in both the univariate and multivariate analyses. Patients with late AKI, but not those with early AKI, had a significantly prolonged length of stay (19.6 vs. 9.6 days, p = 0.015). Conclusion: Our findings show that admission SOFA score was an independent risk factor for AKI in COVID-19 patients, and patients with AKI had higher in-hospital mortality. Moreover, AKI development after 72 h of admission was related to prolonged hospitalization time.

A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.

It is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs).We conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors.A total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group (The appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistant

BackgroundElderliness is known risk factor for severe progression of COVID-19 due to compromised immunity, however aberrant hyperactive immune response including autoimmunity might be responsible for younger patients.Methods162 patients tested with autoimmunological detections were enrolled, and study of “Severe” cases and “Non-severe” controls was retrospectively analyzed. ResultsMultivariable analysis involving antinuclear autoimmunity manifests correlation of disease severity with middle age and attenuates the risk of age older than 65. Middle age (45≤age≤65) and female turn out to be the risk factors after hierarchical cluster analysis, before which however sex was not correlated. We find antinuclear autoimmunity to be strongly correlated with severity for the middle-aged (OR= 21.000, 95% CI 4.893- 90.126, p< 0.001) and female (OR= 16.044, 95% CI 4.717- 54.568, p< 0.001), especially for the middle-aged female (Pearson R= 0.770, p< 0.001). Incidence of symptoms fever and chest distress, and complication myocardial injury are statistically more frequent in patients with positive antinuclear antibody, compared with those negative. Severe patients with positive antinuclear antibody possess significantly shorter onset of symptoms to severity time (p= 0.021), indicating quicker progression, and interestingly, present more incidence (21%) of post-remission aggravation, compared with those negative (6%). ConclusionsThe presence of antinuclear autoimmunity potentially makes COVID-19 prone to severe progression, especially for the middle-aged and female, probably even quicker.

Background Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD‐ILD) has not been determined. Methods A two‐stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD‐ILD cases, and 225 controls). Results We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212–4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376–4.128, p = 0.002 in stage two). However, we did not observe this association in CTD‐ILD (OR = 1.401, 95% CI = 0.790–2.485, p = 0.248). Conclusion Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD‐ILD., A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis (IPF) (p = 0.002 in allele‐model) but not connective tissue diseases related interstitial lung disease (CTD‐ILD) (p = 0.181 in allele‐model) in Southern Han Chinese.

BACKGROUND: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. METHODS: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma‐related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next‐generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). RESULTS: First, we identified 18 potentially functional rare loss‐of‐function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p

Following publication of the original article [1], we were notified that a funding note needs to be added to the Funding section: "Ministry of Science and Technology of the People’s Republic of China (Grant No 2020YFC0845500) " The original paper has been corrected © 2021, The Author(s)

Since the coronavirus disease 2019 (COVID-19) identified in Wuhan, Hubei, China in December 2019, it has been characterized as a pandemic by World Health Organization (WHO). It was reported that asymptomatic persons are potential sources of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present an outbreak among health-care workers incited by a doctor who cared a patient with COVID-19 in a Hospital in Wuhan, Hubei, China, which indicates existence of super-spreader even during incubation period.

Purpose To describe the radiological features of coronavirus disease 19 (COVID-19) and to explore the significant signs that indicate severity of disease. Materials and methods We collected data retrospectively of 180 cases of COVID-19, from 15 January 2020 to 31 March 2020, from both the Wuhan Zhongnan and Beijing Ditan Hospitals, including 103 cases of mild and 77 cases of severe pneumonia. All patients had their first chest computed tomography scan within five days of symptom onset. The dandelion sign was defined by a focal ground glass opacity (GGO) with a central thickening of the airway wall, and the focal crazy paving sign was defined by a focal GGO with thickening of the interlobular septa. Results Consolidation presented in only 4.9% (5/103) of the mild pneumonia cases, which was significantly lower than that in severe pneumonia cases (70.1% 54/77), p

BACKGROUND Different states in the United States had different nonpharmaceutical public health interventions during the COVID-19 pandemic. The effects of those interventions on hospital use have not been systematically evaluated. The investigation could provide data-driven evidence to potentially improve the implementation of public health interventions in the future. OBJECTIVE We aim to study two representative areas in the United States and one area in China (New York State, Ohio State, and Hubei Province), and investigate the effects of their public health interventions by time periods according to key interventions. METHODS This observational study evaluated the numbers of infected, hospitalized, and death cases in New York and Ohio from March 16 through September 14, 2020, and Hubei from January 26 to March 31, 2020. We developed novel Bayesian generalized compartmental models. The clinical stages of COVID-19 were stratified in the models, and the effects of public health interventions were modeled through piecewise exponential functions. Time-dependent transmission rates and effective reproduction numbers were estimated. The associations of interventions and the numbers of required hospital and intensive care unit beds were studied. RESULTS The interventions of social distancing, home confinement, and wearing masks significantly decreased (in a Bayesian sense) the case incidence and reduced the demand for beds in all areas. Ohio’s transmission rates declined before the state’s “stay at home” order, which provided evidence that early intervention is important. Wearing masks was significantly associated with reducing the transmission rates after reopening, when comparing New York and Ohio. The centralized quarantine intervention in Hubei played a significant role in further preventing and controlling the disease in that area. The estimated rates that cured patients become susceptible in all areas were small ( CONCLUSIONS The series of public health interventions in three areas were temporally associated with the burden of COVID-19–attributed hospital use. Social distancing and the use of face masks should continue to prevent the next peak of the pandemic.

COVID-19 has been widely spreading. We aimed to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding. 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n = 37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison (HC). Compared with PA patients, PP patients had much improved laboratory findings. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. Persistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.

Background. Chest CT findings have the potential to guide management in hospitalized patients with COVID-19. Objective. To explore a CT visual severity score in hospitalized patients with COVID-19, with attention to temporal changes in the score and the role of the score in a model for predicting in-hospital complications. Methods. This retrospective study included 161 inpatients with COVID-19 from three hospitals in China who underwent serial chest CT scans during hospitalization. CT examinations were evaluated using a visual severity scoring system. The temporal pattern of the CT visual severity score across serial CT examinations during hospitalization was characterized using a generalized spline regression model. A prognostic model to predict major complications, including in-hospital mortality, was created using the CT visual severity score and clinical variables. External model validation was performed in a cohort of 135 patients from a different hospital, evaluated by two independent radiologists. Results. The cohort included 91 survivors with non-severe disease, 55 survivors with severe disease, and 15 patients who died during hospitalization. Median CT visual lung severity score in the first week of hospitalization was 2.0 in survivors with non-severe disease, 4.0 in survivors with severe disease, and 11.0 in non-survivors. CT visual severity score peaked on hospitalization day 9 and 12 in survivors with non-severe and severe disease, respectively, and progressively decreased in subsequent hospitalization weeks in both groups. In the prognostic model, in-hospital complications were independently associated with a severe CT score (odds ratio [OR] 31.28), moderate CT score (OR 5.86), age (OR 1.09 per year increase), and lymphocyte count (OR 0.03 per 1*10^9/L increase). In the validation cohort, the two readers achieved C-index of 0.92-0.95, accuracy 85.2%-86.7%, sensitivity 70.7%-75.6%, and specificity 91.4%-91.5% for predicting in-hospital complications. Conclusion. A CT visual severity score is associated with clinical disease severity and evolves in a characteristic fashion during hospitalization for COVID-19. A prognostic model based on the CT visual severity score and clinical variables has strong performance in predicting in-hospital complications. Clinical Impact. The prognostic model using the CT visual severity score may help identify patients at highest risk of poor outcomes and guide early intervention.

OBJECTIVES: An ongoing outbreak of coronavirus disease 2019 is spreading globally. Acute hypoxemic respiratory failure is the most common complication of coronavirus disease 2019. However, the clinical effectiveness of early high-flow nasal oxygen treatment in patients with coronavirus disease 2019 with acute hypoxemic respiratory failure has not been explored. This study aimed to analyze the effectiveness of high-flow nasal oxygen treatment and to identify the variables predicting high-flow nasal oxygen treatment failure in coronavirus disease 2019 patients with acute hypoxemic respiratory failure. DESIGN: A multicenter, retrospective cohort study. SETTING: Three tertiary hospitals in Wuhan, China. PATIENTS: Forty-three confirmed coronavirus disease 2019 adult patients with acute hypoxemic respiratory failure treated with high-flow nasal oxygen. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age of the enrolled patients was 63.0 ± 9.7 years; female patients accounted for 41.9%. High-flow nasal oxygen failure (defined as upgrading respiratory support to positive pressure ventilation or death) was observed in 20 patients (46.5%), of which 13 (30.2%) required endotracheal intubation. Patients with high-flow nasal oxygen success had a higher median oxygen saturation (96.0% vs 93.0%; p < 0.001) at admission than those with high-flow nasal oxygen failure. High-flow nasal oxygen failure was more likely in patients who were older (p = 0.030) and male (p = 0.037), had a significant increase in respiratory rate and a significant decrease in the ratio of oxygen saturation/FIO2 to respiratory rate index within 3 days of high-flow nasal oxygen treatment. In a multivariate logistic regression analysis model, male and lower oxygen saturation at admission remained independent predictors of high-flow nasal oxygen failure. The hospital mortality rate of the cohort was 32.5%; however, the hospital mortality rate in patients with high-flow nasal oxygen failure was 65%. CONCLUSIONS: High-flow nasal oxygen may be effective for treating coronavirus disease 2019 patients with mild to moderate acute hypoxemic respiratory failure. However, high-flow nasal oxygen failure was associated with a poor prognosis. Male and lower oxygenation at admission were the two strong predictors of high-flow nasal oxygen failure.

Background: Current information is not enough to recognize the risk factors of clinical deterioration and to make medical decisions in COVID-19 patients. Methods: A retrospective study was performed, with collecting data from medical records of COVID-19 patients in three designated hospitals from January 8, 2020 to May 6, 2020. Clinical data were analyzed between the deteriorated and the non-deteriorated patients, which was defined as either a increase of 2 categories on the modified 6-category ordinal scale, or a decline of PaO2-to-FIO2 ratio more than 100mmHg. Results: Total 238 patients with COVID-19 were selected, where 31 were deteriorated and 207 were non-deteriorated. In the deterioration group, the case fatality rate was up to 41.9%. Compared with non-deteriorated patients, the deteriorated were older (65.8[IQR 54.3-72.3] vs 54.4[41.0-66.1], p=0.004) and were more likely to have chronic medical illnesses (17[54.8%]) vs 92[44.4%]). Multivariable regression showed that three variables, neutrophil-lymphocyte ratio (NLR)≥3.66 (OR, 9.85; 95% CI, 1.68-57.57), hyponatremia (OR, 8.35; 95% CI, 1.74-40.16), and presence of ground-glass opacities with consolidation (OR, 5.84; 95% CI, 1.24-27.49) were associated with increased odds of clinical deterioration. The variable that inspiring air or traditional oxygen therapy only within 72 hours after admission, indicated a decreased odd of illness progression (OR, 0.075; 95% CI, 0.012–0.465).Conclusions: COVID-19 patients with clinical deterioration had more common extra-pulmonary organ impair in early stage and high case fatality rate. Three factors, NLR ≥3.66, hyponatremia and presence of ground-glass opacities with consolidation were determined as high risk factors in deterioration.

From December 25, 2019 to January 31, 2020, 33 cases of the coronavirus disease 2019 (COVID-19) were identified in the Department of Respiratory and Critical Care Medicine of Zhongnan Hospital of Wuhan University, China, yet none of the affiliated HCWs was infected. Here we analyzed the infection control measures used in three different departments in the Zhongnan Hospital of Wuhan University and correlated the measures with the corresponding infection data of HCWs affiliated with these departments. We found that three infection control measures, namely the isolation of the presumed positive patients, the use of facemasks and intensified hand hygiene play important roles in preventing nosocomial transmission of COVID-19.

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) is an emerging infectious disease that first manifested in humans in Wuhan, Hubei Province, China, in December 2019, and has subsequently spread worldwide. Methods We conducted a retrospective, single-center case series of the seven maintenance hemodialysis (HD) patients infected with COVID-19 at Zhongnan Hospital of Wuhan University from 13 January to 7 April 2020 and a proactive search of potential cases by chest computed tomography (CT) scans. Results Of 202 HD patients, 7 (3.5%) were diagnosed with COVID-19. Five were diagnosed by reverse transcription polymerase chain reaction (RT-PCR) because of compatible symptoms, while two were diagnosed by RT-PCR as a result of screening 197 HD patients without respiratory symptoms by chest CT. Thirteen of 197 patients had positive chest CT features and, of these, 2 (15%) were confirmed to have COVID-19. In COVID-19 patients, the most common features at admission were fatigue, fever and diarrhea [5/7 (71%) had all these]. Common laboratory features included lymphocytopenia [6/7 (86%)], elevated lactate dehydrogenase [3/4 (75%)], D-dimer [5/6 (83%)], high-sensitivity C-reactive protein [4/4 (100%)] and procalcitonin [5/5 (100%)]. Chest CT showed bilateral patchy shadows or ground-glass opacity in the lungs of all patients. Four of seven (57%) received oxygen therapy, one (14%) received noninvasive and invasive mechanical ventilation, five (71%) received antiviral and antibacterial drugs, three (43%) recieved glucocorticoid therapy and one (14%) received continuous renal replacement therapy. As the last follow-up, four of the seven patients (57%) had been discharged and three patients were dead. Conclusions Chest CT may identify COVID-19 patients without clear symptoms, but the specificity is low. The mortality of COVID-19 patients on HD was high.

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.

SummaryBackgroundCoronavirus disease 2019 (COVID-19) is an emerging infectious disease.It was first reported in Wuhan, China, and then broke out on a large scale around the world.This study aimed to assess the clinical significance of two different nutritional indices in 245 patients with COVID-19.MethodsIn this retrospective single-center study, we finally included 245 consecutive patients who confirmed COVID-19 in Wuhan University Zhongnan Hospital from January 1 to February 29. Cases were classified as either discharged or dead. Demographic, clinical and laboratory datas were registered, two different nutritional indices were calculated: (i)the Controlling nutritional status (CONUT) score; (ii) prognostic nutritional index (PNI). We used univariate and multivariate logistic regression analysis to explore the relationship between nutritional indices and hospital death.Results212 of them were discharged and 33 of them died. In-hospital mortality was signifcantly higher in the severe group of PNI than in the moderate and normal groups. It was also significantly worse in the severe-CONUT group than in the moderate-, mild-, and normal-CONUT groups. Multivariate logistic regression analysis showed the CONUT score (odds ratio3.371,95%CI (1.124–10.106), p = 0.030) and PNI(odds ratio 0.721,95% CI (0.581–0.896), P=0.003) were independent predictors of all-cause death at an early stage; Multivariate logistic regression analysis also showed that the severe group of PNI was the independent risk predictor of in-hospital death(odds ratio 24.225, 95% CI(2.147–273.327), p=0.010).The CONUT score cutoff value was 5.5 (56.00 and 80.81%; AUC 0.753; 95% CI (0.644–0.862); respectively). The PNI cutoff value was 40.58 (81.80 and 66.20%; AUC 0.778; 95% CI (0.686–0.809); respectively). We use PNI and the COUNT score to assess malnutrition, which can have a prognosis effect of COVID-19patients.ConclusionThe CONUT score and PNI could be a reliable prognostic marker of all-cause deathin patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently spread worldwide partly through environmental and airborne contamination. The number of patients requiring intensive care unit (ICU)-based healthcare services exceeds the available negative-pressure isolation ICU room capacity. Some general wards of Wuhan hospitals have been temporarily converted into COVID-19 ICU wards and pose safety concerns. We explored the safety of these temporary COVID-19 ICU wards.Methods: Fifteen air samples and 128 environmental surface swabs were collected from 14 patients in 4 departments with temporary COVID-19 ICU wards. Quantitative real-time PCR (RT-PCR) methods confirmed the existence of COVID-19 pathogens.Results: Four of the 15 air samples were obtained during aerosol-generating medical procedures (1 tracheostomy, 1 high-flow nasal cannula [HFNC], 1 HFNC+nebulization, 1 non-invasive positive pressure ventilation). Five patients were administered invasive positive pressure ventilation through tracheostomy. All air samples tested negative for SARS-CoV-2 by RT-PCR. Viruses were detected on the surface of a patient’s gastric tube, and an anal tube swab tested positive. Five days later, the anal swab of the patient remained positive, although viral RNA of the nasopharyngeal swap turned negative.Conclusions: Establishing temporary isolation COVID-19 ICU wards is a safe and effective method to increase surge capacity in a hospital. SARS-CoV-2 sheds from the enteric canal after viral clearance in the respiratory tract. Reinforcing disinfection of tubes and circuits given to the patients is essential in COVID-19 isolation wards to decrease nosocomial transmission.

Importance WHO has made the assessment that coronavirus disease 2019 (COVID-19) can be characterized as a pandemic. So far, there is no clinically proven effective antiviral drug for COVID-19. Objective To compare the efficacy and safety of favipiravir and arbidol to treat COVID-19 patients on clinical recovery rate of day 7. Design Prospective, multicenter, open-label, randomized superiority trial in February, 2020. Setting Multicenter study. Participants Patients with confirmed COVID-19 admitted to 3 hospitals from Feb. 20, 2020 to Mar. 12, 2020. Interventions Conventional therapy + favipiravir or arbidol. Main Outcomes and Measures The primary outcome was clinical recovery rate of day 7. Duration of fever, cough relief time and auxiliary oxygen therapy or noninvasive mechanical ventilation rate were the secondary outcomes. The patients with chest CT imaging and laboratory-confirmed COVID-19 infection, aged 18 years or older were randomly assigned to receive favipiravir or arbidol. Safety data were collected for further follow-up for a week. Results 120 patients were assigned to favipiravir group (116 assessed) and 120 to arbidol group (120 assessed). In full analysis set (FAS) cohort, for moderate patients with COVID-19, clinical recovery rate of day 7 was 55.86% in the arbidol group and 71.43% in the favipiravir group (P=0.0199). For moderate COVID-19 patients and COVID-19 patients with hypertension and/or diabetes, the latency to fever reduction and cough relief in favipiravir group was significantly shorter than that in arbidol group (both P 0.05). The most frequently observed treatment-associated adverse events were abnormal LFT, psychiatric symptom reactions, digestive tract reactions and raised serum uric acid (3 [2.50%] in arbidol group vs 16 [13.79%] in favipiravir group, P Conclusions and Relevance In moderate COVID-19 patients untreated with antiviral previously, favipiravir can be considered as a preferred treatment compared to arbidol because of superior clinical recovery rate of day 7 and more effectively reduced incidence of fever, cough besides some manageable antiviral-associated adverse effects. Trial Registration This study is registered with Chictr.org.cn, number ChiCTR2000030254. Key points Question How about the efficacy and safety of favipiravir to treat COVID-19 patients? Findings Compared to arbidol, in moderate COVID-19 patients untreated with antiviral previously, favipiravir shown superior efficacy in terms of clinical recovery rate of day 7 and reduced incidence of fever, cough with manageable antiviral-associated adverse effects. Meaning Favipiravir can be considered as a preferred treatment approach to moderate COVID-19 pneumonia.