Background: The coronavirus disease 2019 outbreak is evolving rapidly worldwide. Objective: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. Methods: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. Results: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. Conclusion: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes. This article has supplementary material available from

Please cite this article as: Liang W-hua, Guan W-jie, Li C-chen, et al. Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicenter) and outside Hubei (non-epicenter): A Nationwide Analysis of China. Eur Respir J 2020; in press (https://doi.Abstract BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China has been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS:Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalized COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients in and outside of Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicenter as well the administrative center of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS:Upon data cut-off (Jan 31st, 2020), 1,590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597/647, 92.3%) were older (mean: 49.7 vs. 44.9 years), had more cases with comorbidity (32.9% vs. 19.7%), higher symptomatic burden, abnormal radiologic manifestations, and, especially, a longer waiting time between symptom onset and admission (5.7 vs. 4.5 days) compared with patients outside Hubei. Patients in Hubei [severe event rate 23.0% vs. 11.1%, death rate 7.3% vs. 0.3%, hazards ratio (HR) for critical illness 1.59, 95%CI 1.05-2.41] have a poorer prognosis compared with patients outside of Hubei after adjusting for age and comorbidity. However, among patients outside of Hubei, the duration from symptom onset to hospitalization (mean: 4.4 vs. 4.7 days) and prognosis (HR 0.84, were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR 1.05, 1.01-1.08).CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalization in the epicenter. Future studies to determine the reason for delaying hospitalization are warranted.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

In this work, the fluid flow and mass transfer due to the presence of an electric field in a rectangular channel is examined. We consider a mixture of water or another neutral solvent and a salt compound, such as sodium chloride, for which the ionic species are entirely dissociated. Results are produced for the case in which the channel height is much greater than the electric double layer (EDL) (microchannel) and for the case in which the channel height is of the order of the width of the EDL (nanochannel). Both symmetric and nonsymmetric velocity, potential, and mole fraction distributions are considered, unlike previous work on this problem. At small electrolyte concentrations, the Debeye-Huckel picture of the electric double layer is recovered; at larger concentrations, the Gouy-Chapman picture of the electric double emerges naturally. The numerical results presented here agree with analytical solutions of a singular perturbation analysis, which is valid as the channel height increases. In the symmetric case for the electroosmotic flow so induced, the velocity field and the potential are similar. In the asymmetric case corresponding to different wall potentials, the velocity and potential can be vastly different. The fluid is assumed to behave as a continuum, and the volume flow rate is observed to vary linearly with channel height for electrically driven flow, in contrast to pressure-driven flow, which varies as height cubed. This means that very large pressure drops are required to drive flows in small channels. However, useful volume flow rates may be obtained at a very low driving voltage.

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Experimental studies were carried out on fully developed and steady electro-osmotic flow in a rectangular channel where the channel height $h$ is comparable to its width and the thickness of the electric double layer characterized by the Debye length is much less than $h$. The nano-particle image velocimetry technique was used to measure the two components of the velocity field parallel to and within about 100 nm of the channel wall for $h\,{\leq}\,25\,\umu$m. The mobility of the particle tracers was calculated from averaged velocity data for various electric field strengths. The experimentally determined mobility values are compared with analytical predictions for dilute aqueous solutions of sodium tetraborate.

COVID-19 is a widespread and highly contagious disease in the human population.

Hepatitis C virus (HCV) infection is a serious and rising global healthcare problem. One critical challenge to tackle this disease is the lack of adequate diagnosis. Here, we develop a multiplex microfluidic paper-based immunoassay, as a novel diagnostic approach, to detect human IgG antibody against HCV (anti-HCV). The paper substrate, highly flammable nitrocellulose (NC), is patterned under ambient temperature by craft punch patterning (CPP) to generate multiple test zones. On the basis of superior merits of patterned paper, this new diagnostic approach demonstrates the key novelty to unprecedentedly combine segmented diagnostic assays into a single multiplex test. The generated diagnostic results are not only informative but can be rapidly and cost-effectively delivered. It would significantly transform the clinical pathway for unwitting individuals with HCV infection. This work highlights the promising role of microfluidic paper-based immunoassays in tackling the diagnostic challenge for the HCV pandemic as well as other diseases.