Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents.

Introduction: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies. Methods: In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies. Results and discussion: We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.

Discovery of novel bicyclic[3.3.0]proline peptidyl α-ketoamides as potent 3CL-protease inhibitors for SARS-CoV-2.

The outbreak of SARS-CoV-2 has caused global crisis on health and economics. The multiple drug-drug interaction risk associated with ritonavir warrants specialized assessment before using Paxlovid. Here we report a multiple-round SAR study to provide a novel bicyclic[3.3.0]proline peptidyl α-ketoamide compound 4a, which is endowed with excellent antiviral activities and pharmacokinetic properties. Also, in vivo HCoV-OC43 neonatal mice model demonstrated compound 4a has good in vivo efficacy. Based on these properties, compound 4a worth further SAR optimization with the goal to develop compounds with better pharmacokinetic properties and finally to realize single agent efficacy in human.

Data-driven product ranking: A hybrid ranking approach

The sudden COVID-19 epidemic has caused consumers to gradually switch to online shopping, the increasing number of online consumer reviews (OCR) on Web 2.0 sites has made it difficult for consumers and merchants to make decisions by analyzing OCR. Much of the current literature on ranking products based on OCR ignores neutral reviews in OCR, evaluates mostly given criteria and ignores consumers' own purchasing preferences, or ranks based on star ratings alone. This study aims to propose a new decision support framework for the evaluation and selection of alternative products based on OCR. The decision support framework mainly includes three parts: 1) Data preprocessing: using Python to capture online consumer comments for data cleaning and preprocessing, and extracting key features as evaluation criteria;2) Sentiment analysis: using Naive Bayes to analyze the sentiment of OCR, and using intuitionistic fuzzy sets to describe the emotion score;3) Benchmark analysis: a new IFMBWM-DEA model considering the preference of decision makers is proposed to calculate the efficiency score of alternative schemes and rank them according to the efficiency score. Then, the OCR of 15 laptops crawled from JD.com platform is used to prove the usefulness and applicability of the proposed decision support framework in two aspects: on the one hand, the comparison of whether the preference of decision makers is considered, and on the other hand, the comparison with the existing ranking methods. The comparison also proves that the proposed method is more realistic, the recommendations are more scientific and the complexity of the decision is reduced. [ FROM AUTHOR] Copyright of Journal of Intelligent & Fuzzy Systems is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Double challenges: How working from home affects dual-earner couples' work-family experiences

Against the backdrop of COVID-19 pandemic, we draw on family systems theory to elucidate how daily work-from-home status (WFH) affects both members in dual-earner couples. We propose that the WFH exerts intra-individual and inter-individual influences on employees' and their partners' work task and family task completion and their subsequent reactions to their work and family experiences. We examined the hypothesized relationships with two daily survey studies on dual-earner couples conducted during the pandemic (i.e., 1,559 daily responses of 165 dual-earner couples from China in Study 1, and 773 daily responses of 57 dual-earner couples from South Korea in Study 2). The two studies provide converging results that working from home (vs. office) increased employees' family task completion for both husbands and wives and that wives working from home (vs. office) decreased husbands' family task completion. Further, in both studies, daily work task completion increased felt guilt toward family (for wives only) through increased work-family conflict, and daily family task completion increased psychological withdrawal from work through increased family-work conflict for both husbands and wives. Moreover, we found in Study 2 that on days when husbands had flexible work schedule, wives completed more work tasks when working from home (vs. office) and that on days when wives had inflexible work arrangement, husbands completed more family tasks when working from home (vs. office). Across the two studies, there were no clear gender-difference patterns in husbands' and wives' work and family experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Double challenges: How working from home affects dual-earner couples' work-family experiences

Against the backdrop of COVID-19 pandemic, we draw on family systems theory to elucidate how daily work-from-home status (WFH) affects both members in dual-earner couples. We propose that the WFH exerts intra-individual and inter-individual influences on employees' and their partners' work task and family task completion and their subsequent reactions to their work and family experiences. We examined the hypothesized relationships with two daily survey studies on dual-earner couples conducted during the pandemic (i.e., 1,559 daily responses of 165 dual-earner couples from China in Study 1, and 773 daily responses of 57 dual-earner couples from South Korea in Study 2). The two studies provide converging results that working from home (vs. office) increased employees' family task completion for both husbands and wives and that wives working from home (vs. office) decreased husbands' family task completion. Further, in both studies, daily work task completion increased felt guilt toward family (for wives only) through increased work-family conflict, and daily family task completion increased psychological withdrawal from work through increased family-work conflict for both husbands and wives. Moreover, we found in Study 2 that on days when husbands had flexible work schedule, wives completed more work tasks when working from home (vs. office) and that on days when wives had inflexible work arrangement, husbands completed more family tasks when working from home (vs. office). Across the two studies, there were no clear gender-difference patterns in husbands' and wives' work and family experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Rational development of multicomponent mRNA vaccine candidates against mpox.

The re-emerging mpox (formerly monkeypox) virus (MPXV), a member of Orthopoxvirus genus together with variola virus (VARV) and vaccinia virus (VACV), has led to public health emergency of international concern since July 2022. Inspired by the unprecedent success of coronavirus disease 2019 (COVID-19) mRNA vaccines, the development of a safe and effective mRNA vaccine against MPXV is of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we rationally constructed and prepared a panel of multicomponent MPXV vaccine candidates encoding different combinations of viral antigens including M1R, E8L, A29L, A35R, and B6R. In vitro and in vivo characterization demonstrated that two immunizations of all mRNA vaccine candidates elicit a robust antibody response as well as antigen-specific Th1-biased cellular response in mice. Importantly, the penta- and tetra-component vaccine candidates AR-MPXV5 and AR-MPXV4a showed superior capability of inducing neutralizing antibodies as well as of protecting from VACV challenge in mice. Our study provides critical insights to understand the protection mechanism of MPXV infection and direct evidence supporting further clinical development of these multicomponent mRNA vaccine candidates.

Early Clinical Development of Lufotrelvir as a Potential Therapy for COVID-19

Lufotrelvir was designed as a first in class 3CL protease inhibitor to treat COVID-19. Development of lufotrelvir was challenged by its relatively poor stability due to its propensity to epimerize and degrade. Key elements of process development included improvement of the supply routes to the indole and lactam fragments, a Claisen addition to homologate the lactam, and a subsequent phosphorylation reaction to prepare the prodrug as well as identification of a DMSO solvated form of lufotrelvir to enable long-term storage. As a new approach to preparing the indole fragment, a Cu-catalyzed C–O coupling using oxalamide ligands was demonstrated. The control of process-related impurities was essential to accommodate the parenteral formulation. Isolation of an MEK solvate followed by the DMSO solvate ensured that all impurities were controlled appropriately.

Understanding metabolic alterations after SARS-CoV-2 infection: insights from the patients' oral microenvironmental metabolites.

BACKGROUND: Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection. METHODS: Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students' t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application. RESULTS: PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body's metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites. CONCLUSIONS: This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.

Spatiotemporal cluster analysis and socio-economic influencing factors of COVID-19 epidemic situation in Hubei Province

Exploring the temporal and spatial clustering characteristics of the new type of corona virus pneumonia(corona virus disease 2019, COVID-19) in Hubei Province and the socio-economic influencing factors have essential reference value for epidemic prevention and control. This paper conducted a spatiotemporal cluster analysis of the COVID-19 epidemic data in Hubei Province. According to the clustering results, different epidemic development stages were divided. Spearman correlation analysis was used to analyze the economic and social factors affecting the epidemic development in Hubei Province (except Wuhan City). The results of spatiotemporal cluster analysis showed that the first level spatiotemporal cluster area was Wuhan City from January 31 to February 20, 2020, and the relative risk was 29.08. The second level spatiotemporal cluster areas were Xiaogan, Suizhou, Xiantao, Jingzhou, Jingmen, Yichang, Tianmen, and Qianjiang cities from January 31 to February 6, 2020, and the average relative risk was 1.60. Relative risk(RR) can quantitatively reflect the degree of epidemic risk in a region, help classify risk levels, allocate resources rationally, and formulate epidemic prevention measures. Exploring the socio-economic factors affecting the spread of the epidemic in stages has a great significance to studying the spread of the epidemic. Population density, gross domestic product(GDP) per capita, the proportion of Wuhan's immigrant population, and the intensity of travel within the city have an important impact on the spread of the epidemic. Per capita GDP is the main factor affecting the incidence rate of the epidemic. During the rapid development period, the proportion of the immigrant population and the intensity of travel in Wuhan are important indicators. The "primary transmission" of close contact between the incoming population and the local population in Wuhan plays a major role in the spread of the epidemic. The population density and the proportion of the immigrant population in Wuhan during the outbreak period are the important influencing factors of the epidemic. The community family gathering transmission is the main transmission mode of the epidemic at this stage. In the process of epidemic prevention and control, targeted measures should be implemented according to the differences of epidemic transmission modes in different periods, such as strengthening the publicity of epidemic prevention and control in the early stage of the epidemic, improving personal awareness of epidemic prevention, paying attention to the prevention and control of the imported population, and controlling population flow. In the middle and late stages of the epidemic, we should focus on preventing and controlling local transmission, strengthening the prevention and control of community and gathering activities, maintaining social distance in public places, and effectively preventing the rebound of the epidemic.

Double challenges: How working from home affects dual-earner couples' work-family experiences

Against the backdrop of COVID-19 pandemic, we draw on family systems theory to elucidate how daily work-from-home status (WFH) affects both members in dual-earner couples. We propose that the WFH exerts intra-individual and inter-individual influences on employees' and their partners' work task and family task completion and their subsequent reactions to their work and family experiences. We examined the hypothesized relationships with two daily survey studies on dual-earner couples conducted during the pandemic (i.e., 1,559 daily responses of 165 dual-earner couples from China in Study 1, and 773 daily responses of 57 dual-earner couples from South Korea in Study 2). The two studies provide converging results that working from home (vs. office) increased employees' family task completion for both husbands and wives and that wives working from home (vs. office) decreased husbands' family task completion. Further, in both studies, daily work task completion increased felt guilt toward family (for wives only) through increased work-family conflict, and daily family task completion increased psychological withdrawal from work through increased family-work conflict for both husbands and wives. Moreover, we found in Study 2 that on days when husbands had flexible work schedule, wives completed more work tasks when working from home (vs. office) and that on days when wives had inflexible work arrangement, husbands completed more family tasks when working from home (vs. office). Across the two studies, there were no clear gender-difference patterns in husbands' and wives' work and family experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Pre-existing anti-HCoV-OC43 immunity influences the durability and cross-reactivity of humoral response to SARS-CoV-2 vaccination.

Purpose: This study was conducted in order to properly understand whether prior seasonal human coronavirus (HCoV) immunity could impact the potential cross-reactivity of humoral responses induced by SARS-CoV-2 vaccine, thereby devising universal coronavirus vaccines for future outbreaks. Methods: We performed enzyme-linked immunosorbent assay (ELISA) to quantify the immunoglobulin G (IgG) antibody levels to spike (S) protein and S1 subunit of HCoVs (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E), and ELISA [anti-RBD and anti-nucleoprotein (N)], chemiluminescence immunoassay assays (anti-RBD), pseudovirus neutralization test, and authentic viral neutralization test to detect the binding and neutralizing antibodies to SARS-CoV-2 in the vaccinees. Results: We found that the antibody of seasonal HCoVs did exist before vaccination and could be boosted by SARS-CoV-2 vaccine. A further analysis demonstrated that the prior S and S1 IgG antibodies of HCoV-OC43 were positively correlated with anti-RBD and neutralization antibodies to SARS-CoV-2 at 12 and 24 weeks after the second vaccination, and the correlation is more statistically significant at 24 weeks. The persistent antibody levels of SARS-CoV-2 were observed in vaccinees with higher pre-existing HCoV-OC43 antibodies. Conclusion: Our data indicate that inactivated SARS-CoV-2 vaccination may confer cross-protection against seasonal coronaviruses in most individuals, and more importantly, the pre-existing HCoV-OC43 antibody was associated with protective immunity to SARS-CoV-2, supporting the development of a pan-coronavirus vaccine.

An Investigation into the Aging of Disposable Face Masks in Landfill Leachate

Due to the excessive use of disposable face masks during the Covid-19 pandemic, their accumulation has posed a great threat to the environment. In this study, we explored the fate of masks after being disposed in landfill. We simulated the possible process that masks would experience, including the exposure to sunlight before being covered and the contact with landfill leachate. After exposure to UV radiation, all three mask layers exhibited abrasions and fractures on the surface and became unstable with the increased UV radiation duration showed aging process. The alterations in chemical groups of masks as well as the lower mechanical strength of masks after UV weathering were detected to prove the happened aging process. Then it was found that the aging of masks in landfill leachate was further accelerated compared to these processes occurring in deionized water. Furthermore, the carbonyl index and isotacticity of the mask samples after aging for 30 days in leachate were higher than those of pristine materials, especially for those endured longer UV radiation. Similarly, the weight and tensile strength of the aged masks were also found lower than the original samples. Masks were likely to release more microparticles and high concentration of metal elements into leachate than deionized water after UV radiation and aging. After being exposed to UV radiation for 48h, the concentration of released particles in leachate was 39.45μL/L after 1 day and then grew to 309.45μL/L after 30 days of aging. Seven elements (Al, Cr, Cu, Zn, Cd, Sb and Pb) were detected in leachate and the concentration of this metal elements increased with the longer aging time. The findings of this study can advance our understanding of the fate of disposable masks in the landfill and develop the strategy to address this challenge in waste management.

Clinical efficacy analysis of mesenchymal stem cell therapy in patients with COVID-19: A systematic review.

BACKGROUND: Currently, ongoing trials of mesenchymal stem cells (MSC) therapies for coronavirus disease 2019 (COVID-19) have been reported. AIM: In this study, we investigated whether MSCs have therapeutic efficacy in novel COVID-19 patients. METHODS: Search terms included stem cell, MSC, umbilical cord blood, novel coronavirus, severe acute respiratory syndrome coronavirus-2 and COVID-19, applied to PubMed, the Cochrane Controlled Trials Register, EMBASE and Web of Science. RESULTS: A total of 13 eligible clinical trials met our inclusion criteria with a total of 548 patients. The analysis showed no significant decrease in C-reactive protein (CRP) levels after stem cell therapy (P = 0.11). A reduction of D-dimer levels was also not observed in patients after stem cell administration (P = 0.82). Furthermore, interleukin 6 (IL-6) demonstrated no decrease after stem cell therapy (P = 0.45). Finally, we investigated the overall survival (OS) rate after stem cell therapy in COVID-19 patients. There was a significant improvement in OS after stem cell therapy; the OS of enrolled patients who received stem cell therapy was 90.3%, whereas that of the control group was 79.8% (P = 0.02). CONCLUSION: Overall, our analysis suggests that while MSC therapy for COVID-19 patients does not significantly decrease inflammatory markers such as CRP, D-dimer and IL-6, OS is improved.

Emergency logistics network optimization with time window assignment.

During natural disasters or accidents, an emergency logistics network aims to ensure the distribution of relief supplies to victims in time and efficiently. When the coronavirus disease 2019 (COVID-19) emerged, the government closed the outbreak areas to control the risk of transmission. The closed areas were divided into high-risk and middle-/low-risk areas, and travel restrictions were enforced in the different risk areas. The distribution of daily essential supplies to residents in the closed areas became a major challenge for the government. This study introduces a new variant of the vehicle routing problem with travel restrictions in closed areas called the two-echelon emergency vehicle routing problem with time window assignment (2E-EVRPTWA). 2E-EVRPTWA involves transporting goods from distribution centers (DCs) to satellites in high-risk areas in the first echelon and delivering goods from DCs or satellites to customers in the second echelon. Vehicle sharing and time window assignment (TWA) strategies are applied to optimize the transportation resource configuration and improve the operational efficiency of the emergency logistics network. A tri-objective mathematical model for 2E-EVRPTWA is also constructed to minimize the total operating cost, total delivery time, and number of vehicles. A multi-objective adaptive large neighborhood search with split algorithm (MOALNS-SA) is proposed to obtain the Pareto optimal solution for 2E-EVRPTWA. The split algorithm (SA) calculates the objective values associated with each solution and assigns multiple trips to shared vehicles. A non-dominated sorting strategy is used to retain the optimal labels obtained with the SA algorithm and evaluate the quality of the multi-objective solution. The TWA strategy embedded in MOALNS-SA assigns appropriate candidate time windows to customers. The proposed MOALNS-SA produces results that are comparable with the CPLEX solver and those of the self-learning non-dominated sorting genetic algorithm-II, multi-objective ant colony algorithm, and multi-objective particle swarm optimization algorithm for 2E-EVRPTWA. A real-world COVID-19 case study from Chongqing City, China, is performed to test the performance of the proposed model and algorithm. This study helps the government and logistics enterprises design an efficient, collaborative, emergency logistics network, and promote the healthy and sustainable development of cities.

Experiences of dental clinical trials management under COVID-19 in China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. Despite progress in pandemic prevention and control, it has always been a difficult task for China to pursue a 'zero COVID-19' strategy. Given the aerosol transmission of COVID-19 and the strict nosocomial infection control in dental hospitals, the execution of clinical trials in oral, dental and craniofacial research have encountered heightened difficulties. During this wave of the pandemic, the Institute of Clinical Trials in our hospital has continuously organised experts to discuss how to improve the management of clinical trials and we have made improvements in their management with the following principles: subject protection being our priority, humanised service being our pursuit and the quality of clinical trials being the cornerstone. Here, we share our experiences and current practices in clinical trial management with our peers worldwide, aiming to promote the management of clinical trials and contribute to the development of stomatology under the constraints of COVID-19 waves.

Emergency logistics network optimization with time window assignment

During natural disasters or accidents, an emergency logistics network aims to ensure the distribution of relief supplies to victims in time and efficiently. When the coronavirus disease 2019 (COVID-19) emerged, the government closed the outbreak areas to control the risk of transmission. The closed areas were divided into high-risk and middle-/low-risk areas, and travel restrictions were enforced in the different risk areas. The distribution of daily essential supplies to residents in the closed areas became a major challenge for the government. This study introduces a new variant of the vehicle routing problem with travel restrictions in closed areas called the two-echelon emergency vehicle routing problem with time window assignment (2E-EVRPTWA). 2E-EVRPTWA involves transporting goods from distribution centers (DCs) to satellites in high-risk areas in the first echelon and delivering goods from DCs or satellites to customers in the second echelon. Vehicle sharing and time window assignment (TWA) strategies are applied to optimize the transportation resource configuration and improve the operational efficiency of the emergency logistics network. A tri-objective mathematical model for 2E-EVRPTWA is also constructed to minimize the total operating cost, total delivery time, and number of vehicles. A multi-objective adaptive large neighborhood search with split algorithm (MOALNS-SA) is proposed to obtain the Pareto optimal solution for 2E-EVRPTWA. The split algorithm (SA) calculates the objective values associated with each solution and assigns multiple trips to shared vehicles. A non-dominated sorting strategy is used to retain the optimal labels obtained with the SA algorithm and evaluate the quality of the multi-objective solution. The TWA strategy embedded in MOALNS-SA assigns appropriate candidate time windows to customers. The proposed MOALNS-SA produces results that are comparable with the CPLEX solver and those of the self-learning non-dominated sorting genetic algorithm-II, multi-objective ant colony algorithm, and multi-objective particle swarm optimization algorithm for 2E-EVRPTWA. A real-world COVID-19 case study from Chongqing City, China, is performed to test the performance of the proposed model and algorithm. This study helps the government and logistics enterprises design an efficient, collaborative, emergency logistics network, and promote the healthy and sustainable development of cities.

Vitamin D deficiency relation to sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children: A meta-analysis.

INTRODUCTION: Vitamin D deficiency in children is related to the augmented risk of bone illnesses, but its effect on critically ill children is still conflicting. This meta-analysis study was performed to assess the relationship between vitamin D deficiency in children and sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and duration of mechanical ventilation in critically ill children. METHODS: Through a systematic literature search up to June 2020, 16 studies with 2382 children, 1229 children of them with vitamin D deficiency, were found recording relationships between vitamin D deficiency and sepsis, paediatric risk of mortality III score, need for ventilation support, length of hospital stay, and/or duration of mechanical ventilation. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated between vitamin D deficiency children to non-vitamin D deficiency children on the different outcomes in critically ill children using the dichotomous or continuous methods with a random or fixed-effect model. RESULTS: The vitamin D deficiency children category had significantly higher sepsis (OR, 2.35; 95% CI, 1.19-4.63, P = .01); paediatric risk of mortality III score (OR, 2.19; 95% CI, 1.13-4.25, P = .02); higher length of hospital stay (OR, 4.26; 95% CI, 0.81-7.70, P = .02); higher duration of mechanical ventilation (OR, 1.89; 95% CI, 0.22-3.56, P = .03) compared with that in the non-vitamin D deficiency children. However, the need for ventilation support in vitamin D deficiency children did not significantly differ from non-vitamin D deficiency children (OR, 2.00; 95% CI, 0.98-4.07, P = .06) with relatively higher results in vitamin D deficiency children. CONCLUSIONS: Vitamin D deficiency in children might have an independent relationship with higher sepsis, paediatric risk of mortality III score, length of hospital stay, and duration of mechanical ventilation. The relation was relative with a higher risk in need for ventilation support with vitamin D deficiency children. This relationship encouraged us to recommend testing vitamin D levels in all critically ill children and providing them with supplemental vitamin D as prophylaxis.

Pre-existing anti-HCoV-OC43 immunity influences the durability and cross-reactivity of humoral response to SARS-CoV-2 vaccination

Purpose This study was conducted in order to properly understand whether prior seasonal human coronavirus (HCoV) immunity could impact the potential cross-reactivity of humoral responses induced by SARS-CoV-2 vaccine, thereby devising universal coronavirus vaccines for future outbreaks. Methods We performed enzyme-linked immunosorbent assay (ELISA) to quantify the immunoglobulin G (IgG) antibody levels to spike (S) protein and S1 subunit of HCoVs (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E), and ELISA [anti-RBD and anti-nucleoprotein (N)], chemiluminescence immunoassay assays (anti-RBD), pseudovirus neutralization test, and authentic viral neutralization test to detect the binding and neutralizing antibodies to SARS-CoV-2 in the vaccinees. Results We found that the antibody of seasonal HCoVs did exist before vaccination and could be boosted by SARS-CoV-2 vaccine. A further analysis demonstrated that the prior S and S1 IgG antibodies of HCoV-OC43 were positively correlated with anti-RBD and neutralization antibodies to SARS-CoV-2 at 12 and 24 weeks after the second vaccination, and the correlation is more statistically significant at 24 weeks. The persistent antibody levels of SARS-CoV-2 were observed in vaccinees with higher pre-existing HCoV-OC43 antibodies. Conclusion Our data indicate that inactivated SARS-CoV-2 vaccination may confer cross-protection against seasonal coronaviruses in most individuals, and more importantly, the pre-existing HCoV-OC43 antibody was associated with protective immunity to SARS-CoV-2, supporting the development of a pan-coronavirus vaccine.

How to Promote Online Education through Educational Software-An Analytical Study of Factor Analysis and Structural Equation Modeling with Chinese Users as an Example

Online learning has emerged as a fresh method to successfully prevent teacher and student gatherings as well as the propagation of viruses in the context of the ongoing influence of the COVID-19. A problem deserving of consideration is how to increase users' desire to participate in online learning through online class APPs, identify the variables that affect users' use of them, and create a useful assessment scale. In this study, user ratings from 68 students who had used an online class APP were collected using the combination of qualitative and quantitative research, and 200 online questionnaires were sent out to complement the interview findings, based on which 328 assessment questionnaires were gathered and 23 valid items were obtained. The influencing elements that had an impact on users' online learning experiences were identified using factor analysis, and the relationships among the components were investigated using structural equation modeling. Perceived benefits are the main influencing factors, subjective norms and functional quality are the direct factors influencing users' perceived benefits, and self-efficacy is influenced by subjective norms while promoting the perception of functional quality. The factors influencing users' use of online class APPs are ultimately identified as perceived benefits, functional quality and self-efficacy. In order to facilitate users' online learning, user psychological traits, social ties and software functions should be integrated into a cohesive system while designing online class APPs.