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Objective: To determine which early‐stage variables best predicted the deterioration of coronavirus disease 2019 (COVID‐19) among community‐isolated people infected with severe acute respiratory syndrome coronavirus 2 and to test the performance of prediction using only inexpensive‐to‐measure variables. Methods: Medical records of 3145 people isolated in two Fangcang shelter hospitals (large‐scale community isolation centers) from February to March 2020 were accessed. Two complementary methods—machine learning algorithms and competing risk survival analyses—were used to test potential predictors, including age, gender, severity upon admission, symptoms (general symptoms, respiratory symptoms, and gastrointestinal symptoms), computed tomography (CT) signs, and comorbid chronic diseases. All variables were measured upon (or shortly after) admission. The outcome was deterioration versus recovery of COVID‐19. Results: More than a quarter of the 3145 people did not present any symptoms, while one‐third ended isolation due to deterioration. Machine learning models identified moderate severity upon admission, old age, and CT ground‐glass opacity as the most important predictors of deterioration. Removing CT signs did not degrade the performance of models. Competing risk models identified age ≥ 35 years, male gender, moderate severity upon admission, cough, expectoration, CT patchy opacity, CT consolidation, comorbid diabetes, and comorbid cardiovascular or cerebrovascular diseases as significant predictors of deterioration, while a stuffy or runny nose as a predictor of recovery. Conclusions: Early‐stage prediction of COVID‐19 deterioration can be made with inexpensive‐to‐measure variables, such as demographic characteristics, severity upon admission, observable symptoms, and self‐reported comorbid diseases, among asymptomatic people and mildly to moderately symptomatic patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-17A, IL-22 and IL-10 have been implicated in the development of chronic obstructive pulmonary disease (COPD), but their expression in COPD is uncertain. Here we investigate the expression of IL-17A, IL-22 and IL-10 in the serum and sputum of COPD patients. Blood samples and induced sputum samples were collected from 94 patients with COPD, 23 healthy smokers, and 22 healthy control non-smokers. IL-17A, IL-22 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). We found that: 1) serum and sputum IL-17A were higher in COPD compared to healthy smokers and non-smokers; 2) serum IL-17A increased with COPD stages, it was inversely correlated with percentage of forced expiratory volume in the first second (FEV1%) reference and positively correlated with C-reactive protein (CRP), Sputum IL-17A levels in the severe COPD patients were positively correlated with sputum neutrophils, and reversely correlated with sputum macraphages ( p < 0.01); 3) serum and sputum IL-22 were significantly higher in COPD and healthy smokers than those in the non-smoker group, sputum IL-22 was similar in severe COPD (stage III and IV), which were higher than those in the other groups ( p < 0.05); and, 4) serum and sputum IL-10 were similiar in COPD and healthy smokers, which were decreased compared to non-smokers. These data suggest that the increased level of IL-17A in serum and sputum plays important roles in the pathogenesis of COPD. The increased sputum IL-22 might also play important roles in the pathogenesis of COPD, while IL-10 secretion might be not only affected by COPD but also by cigarette smoke. [ABSTRACT FROM AUTHOR]

Invasive lung myofibroblasts are the main cause of tissue remodeling in idiopathic pulmonary fibrosis (IPF). A key mechanism contributing to this important feature is aberrant crosstalk between the abnormal/injured lung epithelium and pulmonary fibroblasts. Here, we demonstrate that lungs from patients with IPF and from mice with bleomycin (BLM)-induced pulmonary fibrosis (PF) are characterized by the induction of human epididymis protein 4 (HE4) overexpression in epithelial cells. HE4 knockdown primarily in epithelial cells attenuates BLM-induced PF in mice, whereas the administration of recombinant mouse HE4 exacerbates fibrosis after BLM stimulation. Mechanistic analysis shows that HE4 and annexin II (ANXA2) specific binding enhances the profibrotic phenotype in epithelial cells, and directly promotes lung fibroblast activation, leading to aberrant epithelial-fibroblast crosstalk and the persistent myofibroblast phenotype. The HE4 and ANXA2 binding site is located after the 30th amino acid at the N terminus of the HE4 molecule. Finally, intratracheal administration of HE4 shRNA lentivirus protects mice against BLM-induced PF. These data suggest that HE4 can serve as a potential therapeutic target in the treatment of IPF. HE4 and ANXA2 specific binding enhances the profibrotic phenotype in epithelial cells, and directly promotes lung fibroblast activation, leading to aberrant epithelial-fibroblast crosstalk in pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Center‐based rehabilitation is limited by COVID‐19 infectivity and social distancing policy. We hypothesized that discharged patients benefit from 8‐week home‐based tele‐rehabilitation (tele‐PR) using mobile phones and low‐cost instruments. Methods: The TERCOV (Tele‐rehabilitation in COVID‐19 survivors) is an investigator‐initiated, prospective, multi‐center, real‐world study. After proper assessment, 186 discharge patients received tele‐PR by smartphone, including breathing exercise, respiratory muscle training, aerobic exercise, and resistance training. Physicians, physiotherapists, and nurses provided guidance through smartphone applications. The primary outcome was six‐minute walk distance (6MWD). The secondary outcomes included hand grip, short physical performance battery, maximal inspiratory pressure, maximal expiratory pressure, self‐rating anxiety/depression scale (SAS/SDS), 36‐item short‐form health survey (SF‐36) and international physical activity questionnaire. Results: Dyspnea subgroups were more functionally impaired. After tele‐PR, improvements were observed in exercise capacity(∆6MWD: 16.80 m, 95% CI 1.18–32.42, p < 0.0001), limb muscle function (∆SPPB 0.25 points, 95% CI 0.05–0.46), respiratory muscle strength (∆MIP 16.50 cm H2O, 95% CI 9.22–23.78, p < 0.0001; ∆MEP: 12.09 cm H2O, 95% CI 3.48–20.70, p = 0.0002), health‐related quality of life (∆SF‐36 49.85, 95% CI: 21.01–78.69, p < 0.0001), physical activity(∆HEPA 13.01%, p = 0.0029). Anxiety reduced in patients with mMRC ≥ 2 (∆SAS = −4.19 points, CI −8.16 to −0.22, p = 0.03). Greater change was seen in dyspnea patients. Implications on Physiotherapy Practice: Supervised/semi‐supervised tele‐PR is a promising option during the pandemic. Patients with Dyspnea benefit more. [ABSTRACT FROM AUTHOR]

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. • Ribavirin targets lung cancer cell while sparing normal cells. • Ribavirin potently inhibits lung tumor angiogenesis. • Ribavirin acts on lung cancer via suppressing eIF4E. • Ribavirin augments in vitro and in vivo efficacy of paclitaxel. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. Recently, increasing evidence supports activated inflammation and gasdermin D (GSDMD)-mediated pyroptosis in macrophage are closely associated with ALI. Basic helix-loop-helix family member e40 (Bhlhe40) is a transcription factor that is comprehensively involved in inflammation. However, there is little experimental evidence connecting Bhlhe40 and GSDMD-driven pyroptosis. The study sought to verify the hypothesis that Bhlhe40 is required for GSDMD-mediated pyroptosis in lipopolysaccharide (LPS)-induced inflammatory injury. Method: We performed studies using Bhlhe40-knockout (Bhlhe40 −/−) mice, small interfering RNA (siRNA) targeting Bhlhe40 and pyroptosis inhibitor disulfiram to investigate the potential roles of Bhlhe40 on LPS-induced ALI and the underlying mechanisms. Results: Bhlhe40 was highly expressed in total lung tissues and macrophages of LPS-induced mice. Bhlhe40−/− mice showed alleviative lung pathological injury and inflammatory response upon LPS stimulation. Meanwhile, we found that Bhlhe40 deficiency significantly suppressed GSDMD-mediated pyroptosis in macrophage in vivo and in vitro. By further mechanistic analysis, we demonstrated that Bhlhe40 deficiency inhibited GSDMD-mediated pyroptosis and subsequent ALI by repressing canonical (caspase-1-mediated) and non-canonical (caspase-11-mediated) signaling pathways in vivo and in vitro. Conclusion: These results indicate Bhlhe40 is required for LPS-induced ALI. Bhlhe40 deficiency can inhibit GSDMD-mediated pyroptosis and therefore alleviate ALI. Targeting Bhlhe40 may be a potential therapeutic strategy for LPS-induced ALI. [ABSTRACT FROM AUTHOR]

Few biomarkers distinguish connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF). Latent transforming growth factor-β binding protein-2 (LTBP2), a secreted extracellular matrix protein, is involved in pulmonary fibrosis. However, the role of LTBP2 in differentially diagnosing CTD-ILD and IPF is unclear. In this study, enzyme-linked immunosorbent assays quantified plasma LTBP2 concentrations in 200 individuals (35 healthy controls, 42 CTD patients without ILD, 89 CTD-ILD patients, and 34 IPF patients). CTD-ILD and IPF were further classified based on chest imaging pattern and pulmonary function test results. Plasma LTBP2 levels were significantly elevated in the IPF group compared with the CTD-ILD group. ROC analysis further suggested the possible value of LTBP2 in differentially diagnosing CTD-ILD and IPF. Additionally, CTD-ILD patients with progressive lung fibrosis had higher plasma LTBP2 concentrations than those who did not. Similarly, patients with IPF developing acute exacerbation showed higher plasma LTBP2 levels than those with stable IPF. This is the first study showing that LTBP2 was closely associated with the usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated ILD (RA-ILD). Moreover, the optimal cutoff values of LTBP2 for distinguishing IPF from CTD-UIP/RA-UIP were 33.75 and 38.33 ng/mL with an AUC of 0.682 and 0.681, respectively. Our findings suggest that plasma LTBP2 levels may differentially diagnose CTD-ILD and IPF, and assess their fibrotic activity. Additionally, clinical LTBP2 evaluation may be a great aid to identifying the presence of the UIP pattern in RA-ILD and to discriminating IPF from CTD-UIP, particularly RA-UIP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The balance between M1 and M2 macrophage polarization is involved in the regulation of pulmonary inflammation. Nuclear factor erythroid-derived 2-like 2 (Nfe2l2, also known as Nrf2), a nuclear transcription factor, is reported to play protective roles in acute lung injury (ALI) and inflammation, and increasing evidence indicates that the protective effects of Nrf2 are closely related to autophagy. This study aimed to explore whether Nrf2 is involved in sepsis-induced acute pulmonary injury and inflammation and in the role of macrophage polarization in the process. In the present study, sepsis patients, an Nrf2 knockout mouse that underwent cecal ligation and puncture (CLP), and lipopolysaccharide (LPS)-treated macrophage cell lines were employed to investigate the potential functions of Nrf2 in sepsis-induced lung injury and the underlying mechanisms. Clinical studies showed that the NRF2 mRNA level was inversely correlated with pulmonary inflammation and disease severity in patients with sepsis. Analyses in a CLP-treated Nrf2 knockout mouse model indicated that an Nrf2 deficiency promoted a CLP-induced increase in M1 macrophage polarization and apoptosis and inhibited CLP-induced upregulation of the autophagy level in lung tissues. Experiments in RAW264.7 cells revealed that Nrf2 overexpression inhibited M1 macrophage polarization but promoted M2 macrophage polarization by improving the autophagy, and Nrf2 overexpression promoted PPARγ but inhibited NF-κB nuclear translocation. In conclusion, these results indicate that Nrf2 plays a protective role in sepsis-induced pulmonary injury and inflammation through the regulation of autophagy- and NF-κB/PPARγ-mediated macrophage polarization. [ABSTRACT FROM AUTHOR]

Objectives: To explore the diagnostic value of radiomics in differentiating between lung adenocarcinomas appearing as ground‐glass opacity nodules (GGO) with high‐ and low Ki‐67 expression levels. Materials and Methods: From January 2018 to January 2021, patients with pulmonary GGO who received lung resection were evaluated for potential enrollment. The included GGOs were then randomly divided into a training cohort and a validation cohort with a ratio of 7:3. Logistic regression (LR), decision tree (DT), support vector machines (SVM), and adaboost (AB) were applied for radiomic model construction. Area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the established models. Results: Seven hundred and sixty‐nine patients with 769 GGOs were included in this study. Two hundred and forty‐five GGOs were confirmed to be of high Ki‐67 labeling index (LI). In the training cohort, gender, age, spiculation sign, pleural indentation sign, bubble sign, and maximum 2D diameter of the nodule were found to be significantly different between high‐ and low Ki‐67 LI groups (p < 0.05), and spiculation sign and maximum 2D diameter of the nodule were further confirmed to be risk factors for Ki‐67 LI. The radiomic model established using SVM exhibited an AUC of 0.731 in the validation cohort, which was higher than that of the clinical‐radiographic model (AUC = 0.675). Moreover, radiomic model combining both intra‐ and peri‐nodular features showed better diagnostic efficacy than using intra‐nodular features alone (AUC = 0.731 and 0.720, respectively). Conclusions: The established radiomic model exhibited good diagnostic efficacy in differentiating between lung adenocarcinoma GGOs with high and low Ki‐67 LI, which was higher than the clinical‐radiographic model. Peri‐nodular radiomic features showed added benefits to the radiomic model. As a novel noninvasive method, radiomics have the potential to be applied in the preliminary classification of Ki‐67 expression level in lung adenocarcinoma GGOs. [ABSTRACT FROM AUTHOR]

• Polymyxin-associated nephrotoxicity remains a major concern in the clinical setting • The overall incidence of AKI was 33.5% among 14 Chinese teaching hospitals • Loading dose and use of multiple nephrotoxic drugs are independent risk factors for AKI • Severity of AKI may be higher in patients with elevated baseline creatinine levels This study aimed to assess the current incidence and risk factors for polymyxin B-associated acute kidney injury (AKI) in Chinese hospitals for a more effective clinical use for polymyxin B. This multicenter, retrospective cohort study included patients from 14 Chinese teaching hospitals who received polymyxin B therapy. Univariate and multivariate logistic regression models were used to determine the factors associated with polymyxin B-associated incident AKI. Furthermore, a multivariate logistic regression model was used to identify the independent risk factors for AKI. A total of 251 patients were included in the analysis. The overall incidence of AKI was 33.5%. A multivariate logistic regression model identified the loading dose (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.01–3.38; P = 0.0491) and the use of two or more nephrotoxic drugs (HR, 3.56; 95% CI, 1.55–8.18; P = 0.0029) as independent risk factors for the occurrence of AKI. Meanwhile, the estimated glomerular filtration rate had a protective effect (HR, 0.99; 95% CI, 0.98–0.99; P = 0.0006) on the occurrence of AKI. The daily dose, cumulative dose, and treatment duration of polymyxin B did not affect the occurrence of AKI. The use of polymyxin B loading doses and the combined use of multiple nephrotoxic drugs are independent risk factors for polymyxin B-associated AKI. The severity of AKI may be higher in patients with elevated baseline creatinine levels. [ABSTRACT FROM AUTHOR]

Background Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. Methods In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. Results Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P <.05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P <.05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P <.05). Conclusion In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to describe the use of masks among health care personnel (HCP) exposed to index cases of coronavirus disease 2019 (COVID-19), and to evaluate any association with infection rate.Methods: We did a retrospective, observational study of HCP at Zhongnan Hospital of Wuhan University for the management of COVID-19 (before person-to-person transmission was official confirmed, no additional protection was provided). A questionnaire was given to all staff listed on the roster in the clinical regions providing care for index patients with COVID-19. All participants were surveyed regarding hand-washing and use of surgical masks and gloves and were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were analysed (Student's t test and Pearson χ2 test) for an association between infection and use of personal protective equipment.Results: Exposure of a total of 299 non-infected and 30 infected staff was confirmed. None of the 149 staff who reported use of all three preventative measures (hand-washing and use of gloves and masks) became infect-ed. In contrast, all 30 of the staff who became infected had omitted at least one of the measures. Fewer staff who wore surgical masks (P=0.000003) became infected compared with those who did not. Infections rates were significantly lower in HCP from the internal medicine departments, as these personnel generally wore masks.Conclusion: An association was found between SARS-CoV-2 infection of HCP and the non-use of masks when working with index cases in clinical settings. We recommend that all HCP follow the strict instructions for prevention and treatment of nosocomial infection during intimate contact with COVID-19, especially staff from surgical departments. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

To describe the radiological features of coronavirus disease 19 (COVID-19) and to explore the significant signs that indicate severity of disease. 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. 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 <.001). Multifocal distribution and pure GGOs were observed more frequently in severe cases of pneumonia (p <.05). The dandelion sign was present in 86.4% (89/103) of the mild pneumonia cases, significantly more frequent than those with severe pneumonia (13.0% [10/77], p <.001). The focal crazy paving sign presented in 65.0% (67/103) of the mild pneumonia cases and was significantly more frequent than in severe cases (23.4% [18/77], p <.001). The hospital stay duration of the mild pneumonia group (13.6 ± 7.2 days) was significantly shorter than the severe pneumonia group (26.6 ± 11.7 days, p <.001) Consolidation, pure GGO and multifocal distribution on a CT scan were associated with severe COVID-19. The dandelion and focal crazy paving signs indicate mild COVID-19. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 with ClinicalTrials.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.Funding: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project. [ABSTRACT FROM AUTHOR]

Importance: In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.Objective: To describe the epidemiological and clinical characteristics of NCIP.Design, Setting, and Participants: Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020.Exposures: Documented NCIP.Main Outcomes and Measures: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked.Results: Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0).Conclusions and Relevance: In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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 WHO and 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.Findings: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.Interpretation: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.Funding: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease with poor prognosis. Epithelial-mesenchymal transition (EMT) has been reported to play an important role in IPF. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) cascade, which regulates EMT and oncogenesis, has been implicated in the pathogenesis of IPF. Calpains, Ca2+-dependent cysteine proteinases that mediate controlled proteolysis of many specific substrates including epithelial cell marker E-cadherin, participate in organ fibrosis. Calpain-1 and calpain-2 of calpain family are ubiquitous calpains. ERK1/2 signaling stimulates the ubiquitous calpains activity in cancer development, but whether ERK1/2 signaling mediates the ubiquitous calpains activity in pulmonary fibrosis is unknown. Here we investigated whether inhibition of ERK1/2 signaling and the ubiquitous calpains attenuated experimental pulmonary fibrosis and examined the potential mechanism. Our results showed that inhibition of ERK1/2 signaling and the ubiquitous calpains both attenuated bleomycin (BLM)-induced lung fibrosis in mice. Inhibition of ERK1/2 signaling downregulated the expression of calpain-1 and calpain-2 in vivo and in vitro. We detected decreased E-cadherin expression and increased calpain-1 expression in IPF patients. Inhibition of ERK1/2 signaling and the ubiquitous calpains both suppressed the development of EMT in vivo and in vitro. Our study indicated that inhibition of the ERK1/2-ubiquitous calpains pathway protected pulmonary fibrosis from BLM, possibly via inhibition of EMT. Therefore, targeting ubiquitous calpains may be a potential strategy to attenuate IPF. Image 1 • ERK1/2 signaling regulates the expression of calpain-1 and calpain-2 in pulmonary fibrosis. • Inhibition of the ERK1/2-ubiquitous calpains pathway attenuates BLM-induced pulmonary fibrosis in mice. • Inhibition of the ERK1/2-ubiquitous calpains pathway suppresses the development of EMT in pulmonary fibrosis. [ABSTRACT FROM AUTHOR]