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Risk factors associated with disease severity and length of hospital stay in COVID-19 patients Dear Editor,We read with interest the article in this journal which revealed the critical role of timely supply of medical resources for COVID-19 patients. 1 The pandemic of COVID-19 has placed an enormous burden on health authorities across the world. The virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously known as 2019-nCoV), causes acute respiratory disease with common signs of infection being respiratory symptoms, fever, cough and breathing difficulties. In more severe cases, infection causes pneumonia, lung failure, septic shock, organ failure and risk of death. The WHO reports that 80% of those infected will develop mild symptoms, 14% severe symptoms and 6% will become critically ill. Given the wide clinical spectrum of COVID-19, a key challenge faced by frontline clinical staff is prioritisation of stretched resources. Thus, there is a critical need for robust risk assessment for clinical management.

Background: The number of coronavirus disease 2019 (COVID-19) cases has rapidly increased all over the world. Specific information about immunity in non-survivors with COVID-19 is scarce. This study aimed to analyse the clinical characteristics and abnormal immunity of the confirmed COVID-19 non-survivors. Methods: In this single-centered, retrospective, observational study, we enrolled 125 patients with COVID-19 who were died between January 13 and March 4, 2020 in Renmin Hospital of Wuhan University. A total of 414 randomly recruited patients with confirmed COVID-19 who were discharged from the same hospital during the same period served as control. The demographic, clinical characteristics and laboratory findings at admission, and treatment used in these patients were collected. The immunity-related risk factors associated with in-hospital death were tested by logistic regression models and Receiver Operating Characteristic (ROC) curve.

Recent reports have showed that a proportion of patients with Coronavirus Disease 2019 (COVID-19) presented elevated leukocyte count. Clinical data about these patients is scarce. We aimed to evaluate the clinical findings of patients with COVID-19 who have increased leukocyte at admission. We retrospectively collected the clinical data on the 52 patients who have increased leukocyte count at admission from the 619 patients with confirmed COVID-19 who had pneumonia with abnormal features on chest CT scan in Renmin Hospital of Wuhan University in Wuhan, China, from February 3 to March 3, 2020. The mean age of the 52 patients with increased leukocyte count was 64.7 (SD 11.4) years, 32 (61.5%) were men and 47 (90.4%) had fever. Compared with the patients with non-increased leukocyte count, the patients with increased leukocyte count were significantly older (P < 0.01), were more likely to have underlying chronic diseases (P < 0.01), more likely to develop critically illness (P < 0.01), more likely to admit to an ICU (P < 0.01), more likely to receive mechanical ventilation (P < 0.01), had higher rate of death (P < 0.01) and the blood levels of neutrophil count and the serum concentrations of CRP and IL-6 were significantly increased, (P < 0.01). The older patients with COVID-19 who had underlying chronic disorders are more likely to develop leukocytosis. These patients are more likely to develop critical illness, with a high admission to an ICU and a high mortality rate.

Background: Recent studies have reported altered efficiency in selective brain regions and functional networks in patients with alcohol use disorder (AUD). Inefficient processing can reflect or arise from the disorganization of information being conveyed from place to place. However, it remains unknown whether the efficiency and functional connectivity are altered in large-scale topological organization of patients with AUD.Methods: Resting-state functional magnetic resonance imaging (rsfMRI) data were experimentally collected from 21 right-handed males with AUD and 21 right-handed, age-, gender- and education-matched healthy controls (HCs). Graph theory was used to investigate inter-group differences in the topological parameters (global and nodal) of networks and inter-regional functional connectivity. Correlations between group differences in network properties and clinical variables were also investigated in the AUD group.Results: The brain networks of the AUD group showed decreased global efficiency when compared with the HC group. Besides, increased nodal efficiency was found in the left orbitofrontal cortex (OFC), while reduced nodal efficiency was observed in the right OFC, right fusiform gyrus (FFG), right superior temporal gyrus, right inferior occipital gyrus (IOG), and left insula. Moreover, hypo-connectivity was detected between the right dorsolateral prefrontal cortex (DLPFC) and right superior occipital gyrus (SOG) in the AUD group when compared with the HC group. The nodal efficiency of the left OFC was associated with cognitive performance in the AUD group.Conclusions: AUD patients exhibited alterations in brain network efficiency and functional connectivity, particularly in regions linked to multi-sensory modalities. These disrupted topological properties may help to obtain a more comprehensive understanding of large-scale brain network activity. Furthermore, these data provide a potential neural mechanism of impaired cognition in individuals with AUD.

Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.

COVID-19 is "public enemy number one" and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 −12), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10 −6). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman's Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded.

Background: In allergic asthma, allergen-specific T cells have a Th2-biased phenotype, and it is thought that dendritic cells (DCs) contribute to the induction of allergic immune responses. Therefore, we hypothesized that DCs from allergic asthmatics and healthy donors differ with regard to their preference to induce Th1 or Th2 immune responses. Objectives: To investigate differences in DC-expressed costimulatory molecules and DC-secreted cytokines between allergic asthmatics and healthy donors, and their influence on the Th1- and Th2-type cytokine balance. Methods: Circulating monocytes from patients with allergic asthma and healthy donors were cultured with GM-CSF and IL-4, respectively, for 5 days and subsequently with lipopolysaccharide for 2 days to create mature DCs (mDCs). CD1a, CD83, CD40 and CD86 expression on mDCs was examined using a fluorescence-activated cell sorter. IL-12 and IL-10 secreted by mDCs were measured by ELISA. Naïve cord blood T cells were primed by mDCs from two groups, and IL-4 and IFN-γ production by polarized T-helper cells (Th) was measured by ELISA. Results: (1) CD86 expression on mDCs from allergic asthmatics was higher than that from healthy donors. (2) IL-12, IL-12p40 and IL-10 production by mDCs from allergic asthmatics was significantly lower than that from healthy donors, respectively. (3) IL-4 production by Th cells primed by mDCs from allergic asthmatics was increased compared with that from healthy donors. Conclusions: mDCs from allergic asthmatics preferentially priming naïve T cells towards Th2-cell development might be due to increased expression of CD86 and reduced production of IL-12 and IL-10.