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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.

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.

In December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, and has spread globally. However, the transmission route of SARS-CoV-2 has not been fully understood. In this study, we aimed to investigate SARS-CoV-2 shedding in the excreta of COVID-19 patients. Electronical medical records, including demographics, clinical characteristics, laboratory and radiological findings of enrolled patients were extracted and analyzed. Pharyngeal swab, stool, and urine specimens were collected and tested for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Viral shedding at multiple time points in specimens was recorded, and its correlation analyzed with clinical manifestations and the severity of illness. A total of 42 laboratory-confirmed patients were enrolled, 8 (19.05%) of whom had gastrointestinal symptoms. A total of 28 (66.67%) patients tested positive for SARS-CoV-2 RNA in stool specimens, and this was not associated with the presence of gastrointestinal symptoms and the severity of illness. Among them, 18 (64.29%) patients remained positive for viral RNA in the feces after the pharyngeal swabs turned negative. The duration of viral shedding from the feces after negative conversion in pharyngeal swabs was 7 (6-10) days, regardless of COVID-19 severity. The demographics, clinical characteristics, laboratory and radiologic findings did not differ between patients who tested positive and negative for SARS-CoV-2 RNA in the feces. Viral RNA was not detectable in urine specimens from 10 patients. Our results demonstrated the presence of SARS-CoV-2 RNA in the feces of COVID-19 patients and suggested the possibility of SARS-CoV-2 transmission via the fecal-oral route., (© 2020 Wiley Periodicals, Inc.)

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 30 th 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 6 th February 2020., Trial Registration: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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%.

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (© 2020 The Author(s) Published by S. Karger AG, Basel.)