The Therapeutic Effects of EFNB2-Fc in a Cell Model of Kawasaki Disease.

The EphrinB2/EphB4 signaling pathway involves the regulation of vascular morphogenesis and angiogenesis. However, little is known about EphrinB2/EphB4 in the pathogenesis of Kawasaki disease (KD) and coronary artery aneurysm formation. Hence, this study aimed to explore the role of EphrinB2/EphB4 and the potential therapeutic effect of EphrinB2-Fc in the coronary arterial endothelial injury of KD. The levels of EphB4 were compared between KD patients and healthy children. Human coronary artery endothelial cells (HCAECs) were stimulated with sera from acute KD patients to establish the KD cell model. The overexpression of EphB4 or treatment with EphrinB2-Fc was found to intervene in the cell model. The cell migration, angiogenesis, and proliferation ability were assessed, and the expression of inflammation-related factors was measured. Our study showed that EphB4 showed low expression in both KD patients and the cell model of KD. The EphB4 protein levels in the CECs of CAA+ KD patients were much lower than those in healthy children. EphrinB2-Fc treatment of KD sera-activated HCAECs suppressed cell proliferation, reduced the expression of inflammation-related factors (such as IL-6 and P-selectin), and elevated cell angiogenesis ability. The results reveal that EphrinB2-Fc has a protective function in endothelial cells and has promising clinical applications for protecting vascular endothelium in patients with KD.

Comorbid Asthma Increased the Risk for COVID-19 Mortality in Asia: A Meta-Analysis.

We aimed to explore the influence of comorbid asthma on the risk for mortality among patients with coronavirus disease 2019 (COVID-19) in Asia by using a meta-analysis. Electronic databases were systematically searched for eligible studies. The pooled odds ratio (OR) with 95% confidence interval (CI) was estimated by using a random-effect model. An inconsistency index (I2) was utilized to assess the statistical heterogeneity. A total of 103 eligible studies with 198,078 COVID-19 patients were enrolled in the meta-analysis; our results demonstrated that comorbid asthma was significantly related to an increased risk for COVID-19 mortality in Asia (pooled OR = 1.42, 95% CI: 1.20−1.68; I2 = 70%, p < 0.01). Subgroup analyses by the proportion of males, setting, and sample sizes generated consistent findings. Meta-regression indicated that male proportion might be the possible sources of heterogeneity. A sensitivity analysis exhibited the reliability and stability of the overall results. Both Begg's analysis (p = 0.835) and Egger's analysis (p = 0.847) revealed that publication bias might not exist. In conclusion, COVID-19 patients with comorbid asthma might bear a higher risk for mortality in Asia, at least among non-elderly individuals.

Similarities and differences between MIS-C and KD: a systematic review and meta-analysis.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome with some clinical manifestations similar to Kawasaki disease (KD), which is difficult to distinguish. OBJECTIVE: The study aimed to characterize the demographic characteristics, clinical characteristics, laboratory features, cardiac complications, and treatment of MIS-C compared with KD. STUDY DESIGN: Studies were selected by searching the PubMed, EMBASE and so on before February 28, 2022. Statistical analyses were performed using Review Manager 5.4 software and STATA 14.0. RESULTS: Fourteen studies with 2928 participants were included. MIS-C patients tended to be older and there was no significant difference in the sex ratio. In terms of clinical characteristics, MIS-C patients were more frequently represented with respiratory, gastrointestinal symptoms and shock. At the same time, they had a lower incidence of conjunctivitis than KD patients. MIS-C patients had lower lymphocyte counts, platelet (PLT) counts, erythrocyte sedimentation rates (ESRs), alanine transaminase (ALT), and albumin levels and had higher levels of aspartate transaminase (AST), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin, C-reactive protein (CRP), D-dimer, fibrinogen, ferritin, and creatinine. MIS-C patients had a higher incidence of left ventricle (LV) dysfunction, valvular regurgitation, pericardial effusion, myocarditis, and pericarditis. The incidence of coronary artery lesion (CAL) was lower in MIS-C patients [OR (95% CI): 0.52 (0.29, 0.93), p =0.03], while it was similar in the acute period. MIS-C patients had higher utilization of glucocorticoids (GCs) and lower utilization of intravenous immune globulin (IVIG). CONCLUSIONS: There were specific differences between MIS-C and KD, which might assist clinicians with the accurate recognition of MIS-C and further mechanistic research.

Impact of Media Use on Chinese Public Behavior towards Vaccination with the COVID-19 Vaccine: A Latent Profile Analysis.

(1) Background: research on vaccines has received extensive attention during epidemics. However, few studies have focused on the impact of media use on vaccination behavior and the factors influencing vaccination in groups with different media use degrees; (2) Method: Based on seven items related to media use, a total of 11,031 respondents were categorized by the frequency of media use by using latent profile analysis (LPA). Binary regression analysis was used to study the factors that influence the vaccination behaviors of people with different media use frequencies; (3) Results: All respondents were classified into the following three groups: media use low frequency (9.7%), media use general (67.1%), and media use high frequency (23.2%). Media use low frequency (ß = -0.608, p < 0.001) was negatively associated with COVID-19 vaccination behavior. In the media use low frequency, analysis showed that "aged 41 years or older" ß = 1.784, p < 0.001), had religious belief (ß = 0.075, p < 0.05), were ethnic minorities (ß = 0.936, p < 0.01) and had friends support (ß = 0.923, p < 0.05) were associated with a preference to accept the COVID-19 vaccine. In the media use general, those who aged 41 years old and older (ß = 1.682, p < 0.001), had major depression (ß = 0.951, p < 0.05), had friends support (ß = 0.048, p < 0.001) would be more likely to receive COVID-19 vaccination. However, respondents who live in towns (ß = -0.300, p < 0.01) had lower behaviors to receive vaccination for COVID-19. In the media use high frequency, the respondents who aged 41 or older (ß = 1.010, p < 0.001), were ethnic minorities (ß = 0.741, p < 0.001), had moderate depression (ß = 1.003, p < 0.05) would receive the vaccination for COVID-19 positively; (4) Conclusions: The more occluded the media use is, the less likely the respondents are to get vaccinated against COVID-19. Vaccination behavior is influenced by different factors in groups with different frequencies of media use. Therefore, the government and appropriate departments should make individualized and targeted strategies about COVID-19 vaccination and disseminate the vaccination information to different media use groups.

The Effect of Strict Lockdown on Omicron SARS-CoV-2 Variant Transmission in Shanghai.

Omicron, the current SARS-CoV-2 variant of concern, is much more contagious than other previous variants. Whether strict lockdown could effectively curb the transmission of Omicron is largely unknown. In this retrospective study, we compared the strictness of government lockdown policies in Shanghai and other countries. Based on the daily Omicron case number from 1 March 2022 to 30 April 2022, the effective reproductive numbers in this Shanghai Omicron wave were calculated to confirm the impact of strict lockdown on Omicron transmission. Pearson correlation was conducted to illustrate the determining factor of strict lockdown outcomes in the 16 different districts of Shanghai. After a very strict citywide lockdown since April 1st, the average daily effective reproductive number reduced significantly, indicating that strict lockdown could slow down the spreading of Omicron. Omicron control is more challenging in districts with higher population mobility and lockdown is more likely to decrease the number of asymptomatic carriers than the symptomatic cases. All these findings indicate that the strict lockdown could curb the transmission of Omicron effectively, especially for the asymptomatic spread, and suggest that differentiated COVID-19 prevention and control measures should be adopted according to the population density and demographic composition of each community.

Landscape of Peripheral Blood Mononuclear Cells and Soluble Factors in Severe COVID-19 Patients With Pulmonary Fibrosis Development.

Resulting from severe inflammation and cell destruction, COVID-19 patients could develop pulmonary fibrosis (PF), which remains in the convalescent stage. Nevertheless, how immune response participates in the pathogenesis of PF progression is not well defined. To investigate that question, 12 patients with severe COVID-19 were included in the study. Peripheral mononuclear cell (PBMC) samples were collected shortly after their admission and proceeded for single-cell RNA sequencing (scRNA-seq). After 14 days of discharge, the patients were revisited for chest CT scan. PF index (FI) was computed by AI-assisted CT images. Patients were categorized into FIhi and FIlo based on median of FI. By scRNA-seq analysis, our data demonstrated that frequency of CD4+ activated T cells and Treg cells were approximately 3-fold higher in FIhi patients compared with FIlo ones (p < 0.034 for all). By dissecting the differentially expressed genes, we found an overall downregulation of IFN-responsive genes (STAT1, IRF7, ISG15, ISG20, IFIs, and IFITMs) and S100s alarmins (S100A8, S100A9, S100A12, etc.) in all T-cell clusters, and cytotoxicity-related genes (GZMB, PRF1, and GNLY) in CTLs and γδ T cells in the FIhi cohort, compared with FIlo subjects. The GSEA analysis illustrated decreased expression of genes enriched in IFN signaling, innate immune response, adaptive immune response in T cells, NK cells, and monocytes in FIhi patients compared with FIlo ones. In conclusion, these data indicated that the attenuated IFN-responsive genes and their related signaling pathways could be critical for PF progression in COVID-19 patients.

Personality Effects on Chinese Public Preference for the COVID-19 Vaccination: Discrete Choice Experiment and Latent Profile Analysis Study.

Objective: This study aims to investigate the differences in public vaccination preference for the COVID-19 vaccine with different personality characteristics. Methods: Based on the Big Five Personality Inventory (BFI-10), a total of 1200 respondents were categorized by personality characteristics using Latent Profile Analysis (LPA). The preference of members the public with different personality characteristics for COVID-19 vaccination was investigated based on a discrete choice experiment (DCE). Results: All respondents were divided into three groups, named the General and Stable type (79.67%), Conscientious and Agreeable type (9.5%), and Open and Extroverted type (10.83%). For the percentage importance of vaccine attributes, both the General and Stable type and Conscientious and Agreeable type respondents considered cost to be the most important (41.93% and 34.95% respectively). However, the Open and Extroverted type respondents considered efficacy as the most important (31.05%). In our conditional logit model (CLOGIT), for vaccine adverse effects, the General and Stable type and Conscientious and Agreeable type respondents preferred "very mild", while the Open and Extroverted type preferred "mild" (OR:1.108, 95%CI 0.977-1.256). The Open and Extroverted type had a higher willingness to pay (WTP) for the most preferred vaccine level compared to the other types. Conclusions: The Open and Extroverted respondents have the highest willingness to vaccinate. The General and Stable type and Conscientious and Agreeable respondents think that the cost of the vaccine is the most important attribute, and prefer the mildest side effects. The Open and Extroverted type think that vaccine efficacy is the most important attribute, prefer "mild" side effects, and have higher willingness to pay for their favorite vaccine level.

Stable Long-Term Culture of Human Distal Airway Stem Cells for Transplantation.

There is a population of p63+/Krt5+ distal airway stem cells (DASCs) quiescently located in the airway basal epithelium of mammals, responding to injury and airway epithelial regeneration. They hold the ability to differentiate into multiple pulmonary cell types and can repopulate the epithelium after damage. The current study aims at gaining further insights into the behavior and characteristics of the DASCs isolated from the patient lung and exploring their clinical translational potential. Human DASCs were brushed off through the bronchoscopic procedure and expanded under the pharmaceutical-grade condition. Their phenotype stability in long-term cell culture was analyzed, followed by safety evaluation and tumorigenic analysis using multiple animal models including rodents and nonhuman primate. The chimerism of the human-mouse lung model indicated that DASC pedigrees could give rise to multiple epithelial types, including type I alveolar cells as well as bronchiolar secretory cells, to regenerate the distal lung. Taken together, the results suggested that DASC transplantation could be a promising therapeutic approach for unmet needs in respiratory medicine including the COVID-19-related diseases.

D2A U-Net: Automatic segmentation of COVID-19 CT slices based on dual attention and hybrid dilated convolution.

Coronavirus Disease 2019 (COVID-19) has become one of the most urgent public health events worldwide due to its high infectivity and mortality. Computed tomography (CT) is a significant screening tool for COVID-19 infection, and automatic segmentation of lung infection in COVID-19 CT images can assist diagnosis and health care of patients. However, accurate and automatic segmentation of COVID-19 lung infections is faced with a few challenges, including blurred edges of infection and relatively low sensitivity. To address the issues above, a novel dilated dual attention U-Net based on the dual attention strategy and hybrid dilated convolutions, namely D2A U-Net, is proposed for COVID-19 lesion segmentation in CT slices. In our D2A U-Net, the dual attention strategy composed of two attention modules is utilized to refine feature maps and reduce the semantic gap between different levels of feature maps. Moreover, the hybrid dilated convolutions are introduced to the model decoder to achieve larger receptive fields, which refines the decoding process. The proposed method is evaluated on an open-source dataset and achieves a Dice score of 0.7298 and recall score of 0.7071, which outperforms the popular cutting-edge methods in the semantic segmentation. The proposed network is expected to be a potential AI-based approach used for the diagnosis and prognosis of COVID-19 patients.