Early-stage predictors of deterioration among 3145 nonsevere SARS-CoV-2-infected people community-isolated in Wuhan, China: A combination of machine learning algorithms and competing risk survival analyses.

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.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown ß-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Latent Transforming Growth Factor-ß Binding Protein-2 Regulates Lung Fibroblast-to-Myofibroblast Differentiation in Pulmonary Fibrosis via NF-κB Signaling.

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. The aberrantly activated lung myofibroblasts, predominantly emerging through fibroblast-to-myofibroblast differentiation, are considered to be the key cells in PF, resulting in excessive accumulation of extracellular matrix (ECM). Latent transforming growth factor-ß (TGFß) binding protein-2 (LTBP2) has been suggested as playing a critical role in modulating the structural integrity of the ECM. However, its function in PF remains unclear. Here, we demonstrated that lungs originating from different types of patients with PF, including idiopathic PF and rheumatoid arthritis-associated interstitial lung disease, and from mice following bleomycin (BLM)-induced PF were characterized by increased LTBP2 expression in activated lung fibroblasts/myofibroblasts. Moreover, serum LTBP2 was also elevated in patients with COVID-19-related PF. LTBP2 silencing by lentiviral shRNA transfection protected against BLM-induced PF and suppressed fibroblast-to-myofibroblast differentiation in vivo and in vitro. More importantly, LTBP2 overexpression was able to induce differentiation of lung fibroblasts to myofibroblasts in vitro, even in the absence of TGFß1. By further mechanistic analysis, we demonstrated that LTBP2 silencing prevented fibroblast-to-myofibroblast differentiation and subsequent PF by suppressing the phosphorylation and nuclear translocation of NF-κB signaling. LTBP2 overexpression-induced fibroblast-to-myofibroblast differentiation depended on the activation of NF-κB signaling in vitro. Therefore, our data indicate that intervention to silence LTBP2 may represent a promising therapy for PF.

Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China.

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.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial.

Background: In addition to supportive therapy, antiviral therapy is an effective treatment for coronavirus disease 2019 (COVID-19). Objective: To compare the efficacy and safety of favipiravir and umifenovir (Arbidol) to treat COVID-19 patients. Methods: We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Enrolled patients with initial symptoms within 12 days were randomly assigned in a 1:1 ratio to receive conventional therapy plus Arbidol (200 mg*3/day) or favipiravir (1600 mg*2/first day followed by 600 mg*2/day) for 7 days. The primary outcome was the clinical recovery rate at day 7 of drug administration (relief for pyrexia and cough, respiratory frequency ≤24 times/min; oxygen saturation ≥98%). Latency to relief for pyrexia and cough and the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV)/mechanical ventilation (MV) were the secondary outcomes. Safety data were collected for 17 days. Results: A total of 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive favipiravir (116 assessed), and 120 patients were assigned to receive Arbidol (120 assessed). The clinical recovery rate at day 7 of drug administration did not significantly differ between the favipiravir group (71/116) and Arbidol group (62/120) (p = 0.1396, difference in recovery rate: 0.0954; 95% CI: -0.0305∼0.2213). Favipiravir contributed to relief for both pyrexia (difference: 1.70 days, p < 0.0001) and cough (difference: 1.75 days, p < 0.0001). No difference was observed in the AOT or NMV/MV rate (both p > 0.05). The most frequently observed favipiravir-associated adverse event was increased serum uric acid (16/116, OR: 5.52, p = 0.0014). Conclusion: Among patients with COVID-19, favipiravir, compared to Arbidol, did not significantly improve the clinical recovery rate at day 7. Favipiravir significantly improved the latency to relieve pyrexia and cough. Adverse effects caused by favipiravir are mild and manageable.

Surgical Masks for Protection of Health Care Personnel Against Covid-19: Results from an Observational Study.

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.

Multicenter Study of Temporal Changes and Prognostic Value of a CT Visual Severity Score in Hospitalized Patients With Coronavirus Disease (COVID-19).

BACKGROUND. Chest CT findings have the potential to guide treatment of hospitalized patients with coronavirus disease (COVID-19). OBJECTIVE. The purpose of this study was to assess 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 evaluated by two independent radiologists in a cohort of 135 patients from a different hospital. RESULTS. The cohort included 91 survivors with nonsevere 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 nonsurvivors. CT visual severity score peaked approximately 9 and 12 days after symptom onset in survivors with nonsevere 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 1-year increase), and lymphocyte count (OR, 0.03 per 1 × 109/L increase). In the validation cohort, the two readers achieved C-index values of 0.92-0.95, accuracy of 85.2-86.7%, sensitivity of 70.7-75.6%, and specificity of 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 shows 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.

Clinical outcomes of hemodialysis patients infected with severe acute respiratory syndrome coronavirus 2 and impact of proactive chest computed tomography scans.

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.

Public Health Interventions' Effect on Hospital Use in Patients With COVID-19: Comparative Study.

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 (<0.0001), which indicates that they have little chance to get the infection again. 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.

A super-spreader of SARS-CoV-2 in incubation period among health-care workers.

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.

Dandelion and focal crazy paving signs: the lung CT based predictors for evaluation of the severity of coronavirus disease.

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 < .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). CONCLUSIONS: 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.

Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients.

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.

Seroprevalence of SARS-CoV-2 immunoglobulin antibodies in Wuhan, China: part of the city-wide massive testing campaign.

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.

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.

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.

High-Flow Nasal Oxygen in Coronavirus Disease 2019 Patients With Acute Hypoxemic Respiratory Failure: A Multicenter, Retrospective Cohort Study.

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.

Acute Kidney Injury in Patients with the Coronavirus Disease 2019: A Multicenter Study.

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.

The role of isolation rooms, facemasks and intensified hand hygiene in the prevention of nosocomial COVID-19 transmission in a pulmonary clinical setting.

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.