The influence of single-point mutation D614G on the binding process between human angiotensin-converting enzyme 2 and the SARS-CoV-2 spike protein-an atomistic simulation study† † Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3ra00198a

SARS-CoV-2 has continuously evolved as changes in the genetic code occur during replication of the genome, with some of the mutations leading to higher transmission among human beings. The spike aspartic acid-614 to glycine (D614G) substitution in the spike represents a "more transmissible form of SARS-CoV-2” and occurs in all SARS-CoV-2 mutants. However, the underlying mechanism of the D614G substitution in virus infectivity has remained unclear. In this paper, we adopt molecular simulations to study the contact processes of the D614G mutant and wild-type (WT) spikes with hACE2. The interaction areas with hACE2 for the two spikes are completely different by visualizing the whole binding processes. The D614G mutant spike moves towards the hACE2 faster than the WT spike. We have also found that the receptor-binding domain (RBD) and N-terminal domain (NTD) of the D614G mutant extend more outwards than those of the WT spike. By analyzing the distances between the spikes and hACE2, the changes of number of hydrogen bonds and interaction energy, we suggest that the increased infectivity of the D614G mutant is not possibly related to the binding strength, but to the binding velocity and conformational change of the mutant spike. This work reveals the impact of D614G substitution on the infectivity of the SARS-CoV-2, and hopefully could provide a rational explanation of interaction mechanisms for all the SARS-CoV-2 mutants. SARS-CoV-2 has continuously evolved as changes in the genetic code occur during replication of the genome, with some of the mutations leading to higher transmission among human beings.

COVID-19 Vaccine Hesitancy in China: An Analysis of Reasons through Mixed Methods.

This study aims to investigate the causes of COVID-19 vaccine hesitancy among the Chinese population. The LDA model and content analysis were used to analyze the content of COVID-19 vaccine hesitancy expressed by the Chinese on Weibo from 2020 to 2022, the leading causes of vaccine hesitancy, and the changes in the reasons for vaccine hesitancy over time. The study found that when the Chinese expressed vaccine hesitancy, it usually involved themes such as information access (18.59%), vaccination services (13.91%), and physical illness (13.24%), and topics such as vaccination process (6.83%), allergic diseases (6.59%), and international news (6.43%). Constraints (35.48%), confidence (17.94%), and calculation (15.99%) are the leading causes of vaccine hesitancy on Weibo. These findings provide a comprehensive picture of how the Chinese express vaccine hesitancy in social media and the reasons and changes for vaccine hesitancy, which can help inspire public health experts, health organizations, or governments in various countries to improve the phenomenon of vaccine hesitancy.

The influence of single-point mutation D614G on the binding process between human angiotensin-converting enzyme 2 and the SARS-CoV-2 spike protein-an atomistic simulation study.

SARS-CoV-2 has continuously evolved as changes in the genetic code occur during replication of the genome, with some of the mutations leading to higher transmission among human beings. The spike aspartic acid-614 to glycine (D614G) substitution in the spike represents a "more transmissible form of SARS-CoV-2" and occurs in all SARS-CoV-2 mutants. However, the underlying mechanism of the D614G substitution in virus infectivity has remained unclear. In this paper, we adopt molecular simulations to study the contact processes of the D614G mutant and wild-type (WT) spikes with hACE2. The interaction areas with hACE2 for the two spikes are completely different by visualizing the whole binding processes. The D614G mutant spike moves towards the hACE2 faster than the WT spike. We have also found that the receptor-binding domain (RBD) and N-terminal domain (NTD) of the D614G mutant extend more outwards than those of the WT spike. By analyzing the distances between the spikes and hACE2, the changes of number of hydrogen bonds and interaction energy, we suggest that the increased infectivity of the D614G mutant is not possibly related to the binding strength, but to the binding velocity and conformational change of the mutant spike. This work reveals the impact of D614G substitution on the infectivity of the SARS-CoV-2, and hopefully could provide a rational explanation of interaction mechanisms for all the SARS-CoV-2 mutants.

Linking University Students' Mindfulness to Positive Adjustment Amidst COVID-19 Pandemic: a 6-month Cross-Lagged Panel Design.

Objectives: In the face of a global pandemic, research on wellness-fostering resources is urgently needed, especially with longitudinal designs and diverse samples. According to the mindfulness-to-meaning theory and broaden-and-build theory, this study examined the reciprocal associations among a group of Chinese university students' trait mindfulness, positive and negative affect, and use of positive coping strategies, including positive reappraisal, planning, and seeking of emotional support during the COVID-19 pandemic. Methods: Participants were 247 Hong Kong university students (M age = 20.96, SD = 2.38; female = 86%) who completed survey measures of mindfulness, positive and negative affect, and positive coping strategies at baseline and 6-month follow-up. Data were analysed using a cross-lagged panel design, controlling for participants' age. Results: The proposed reciprocal model exhibited an excellent fit with the data. There was a reciprocal association between trait mindfulness and positive affect over time. However, no significant reciprocal effect was found among mindfulness, negative affect, and positive coping strategies. Conclusions: Theoretically, the current findings extended the two theories to a non-Western population during a critical time and suggested a long-term reciprocal association between positive affect and mindfulness. Our study provided important insight into university students' positive well-being during COVID-19 and demonstrated the wellness-fostering effect of mindfulness.

Examining COVID-19 vaccine attitude using SEM-Artificial Neural Networks approach: a case from Reddit community.

As new coronavirus variants continue to emerge, in order to better address vaccine-related concerns and promote vaccine uptake in the next few years, the role played by online communities in shaping individuals' vaccine attitudes has become an important lesson for public health practitioners and policymakers to learn. Examining the mechanism that underpins the impact of participating in online communities on the attitude toward COVID-19 vaccines, this study adopted a two-stage hybrid structural equation modeling (SEM)-artificial neural networks (ANN) approach to analyze the survey responses from 1037 Reddit community members. Findings from SEM demonstrated that in leading up to positive COVID-19 vaccine attitudes, sense of online community mediates the positive effects of perceived emotional support and social media usage, and perceived social norm mediates the positive effect of sense of online community as well as the negative effect of political conservatism. Health self-efficacy plays a moderating role between perceived emotional support and perceived social norm of COVID-19 vaccination. Results from the ANN model showed that online community members' perceived social norm of COVID-19 vaccination acts as the most important predictor of positive COVID-19 vaccine attitudes. This study highlights the importance of harnessing online communities in designing COVID-related public health interventions and accelerating normative change in relation to vaccination.

Deep learning-based molecular dynamics simulation for structure-based drug design against SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has led to a global pandemic. Deep learning (DL) technology and molecular dynamics (MD) simulation are two mainstream computational approaches to investigate the geometric, chemical and structural features of protein and guide the relevant drug design. Despite a large amount of research papers focusing on drug design for SARS-COV-2 using DL architectures, it remains unclear how the binding energy of the protein-protein/ligand complex dynamically evolves which is also vital for drug development. In addition, traditional deep neural networks usually have obvious deficiencies in predicting the interaction sites as protein conformation changes. In this review, we introduce the latest progresses of the DL and DL-based MD simulation approaches in structure-based drug design (SBDD) for SARS-CoV-2 which could address the problems of protein structure and binding prediction, drug virtual screening, molecular docking and complex evolution. Furthermore, the current challenges and future directions of DL-based MD simulation for SBDD are also discussed.

Post-COVID-19 Development of Transnational Education in China: Challenges and Opportunities

Transnational education is education delivered to students in a country other than the country in which the awarding institution is based. While the outbreak of COVID-19 has significantly affected higher education, transnational education has exhibited its resilience against the pandemic, and has been continuously expanding in China. In parallel with the golden opportunities for the expansion of transnational education in China after the pandemic, a series of challenges resulting from the transnational context needs to be taken into due consideration, and to be properly addressed. In this paper, the opportunities and challenges for the post-COVID-19 development of transnational education in China are systematically discussed, based on the transnational education delivery at a Sino-Foreign cooperative university. Following our observations on opportunities and challenges, several suggestions are proposed, to address the potential challenges for the stable post-COVID-19 development of transnational education in China.

Being Hopeful and Mindful During Adversity: A Longitudinal Study on College Students' Adjustment During COVID-19.

Objectives: The current study examined whether hope and mindfulness were associated with changes in two maladjustment measures, internalizing and externalizing behaviors, during the COVID-19 pandemic and tested sense of coherence as a mediator. The salutogenic theory of health, which posits that sense of coherence is central to individuals' well-being in stressful situations and that individuals derive their sense of coherence from their generalized resistance resources (GRRs), was used to guide the analyses. Methods: On two occasions separated by about 6 months, 253 Hong Kong college students (mean age = 21.0 years at time 1; 86% of them were women) filled in online questionnaires during the COVID-19 outbreaks. Path analysis was conducted to examine the interrelationships among hope and mindfulness, sense of coherence, and internalizing and externalizing behaviors. Results: Results indicated that hope and mindfulness at time 1 were associated with internalizing and externalizing behaviors at time 2, even after controlling for confounding variables and prior levels of internalizing and externalizing behaviors. Moreover, sense of coherence at time 1 significantly mediated these associations. Conclusions: Findings pointed to the potential roles of hope, mindfulness, and sense of coherence in understanding Chinese college students' adjustment during the COVID-19 pandemic. Future research is needed to test whether sense of coherence and behavioral adjustment can be promoted through hope- and mindfulness-based intervention programs. Future research is also needed to examine the interrelationships among health-promoting assets, sense of coherence, and individual adjustment in samples of diverse cultural backgrounds.

Evolution of the plandemic communication network among serial participants on Twitter

The coronavirus pandemic has been accompanied by the spread of misinformation on social media. The Plandemic conspiracy theory holds that the pandemic outbreak was planned to create a new social order. This study examines the evolution of this popular conspiracy theory from a dynamic network perspective. Guided by the analytical framework of network evolution, the current study explores drivers of tie changes in the Plandemic communication network among serial participants over a 4-month period. Results show that tie changes are explained by degree-based and closure-based structural features (i.e. tendencies toward transitive closure and shared popularity and tendencies against in-degree activity and transitive reciprocated triplet) and nodal attributes (i.e. bot probability and political preference). However, a participant’s level of anger expression does not predict the evolution of the observed network. [ABSTRACT FROM AUTHOR] Copyright of New Media & Society is the property of Sage Publications, Ltd. 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19.

Background: The global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection. Methods: A total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3-7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally. Results: We revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients. Conclusions: Our findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.

Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

Case Report: Identification of SARS-CoV-2 in Cerebrospinal Fluid by Ultrahigh-Depth Sequencing in a Patient With Coronavirus Disease 2019 and Neurological Dysfunction.

We reported that the complete genome sequence of SARS-Coronavirus-2 (SARS-CoV-2) was obtained from a cerebrospinal fluid (CSF) sample by ultrahigh-depth sequencing. Fourteen days after onset, seizures, maxillofacial convulsions, intractable hiccups and a significant increase in intracranial pressure developed in an adult coronavirus disease 2019 patient. The complete genome sequence of SARS-CoV-2 obtained from the cerebrospinal fluid indicates that SARS-CoV-2 can invade the central nervous system. In future, along with nervous system assessment, the pathogen genome detection and other indicators are needed for studying possible nervous system infection of SARS-CoV-2.

A Multisite Survey of NICU Healthcare Professionals' Perceptions About Family-Centered Care.

BACKGROUND: Family-centered care contributes to improved outcomes for preterm and ill infants. Little is known about the perceptions of neonatal intensive care unit (NICU) healthcare professionals regarding the degree to which their NICU practices or values family-centered care. PURPOSE: The aims of this study were to describe attitudes and beliefs of NICU healthcare professionals about family-centered care and to explore professional characteristics that might influence those views. METHODS: Data were derived from the baseline phase of a multicenter quasi-experimental study comparing usual family-centered NICU care with mobile-enhanced family-integrated care. Neonatal intensive care unit healthcare professionals completed the Family-Centered Care Questionnaire-Revised (FCCQ-R), a 45-item measure of 9 core dimensions of Current Practice and Necessary Practice for family-centered care. RESULTS: A total of 382 (43%) NICU healthcare professionals from 6 NICUs completed 1 or more of the FCCQ-R subscales, 83% were registered nurses. Total and subscale scores on the Necessary Practice scale were consistently higher than those on the Current Practice scale for all dimensions of family-centered care (mean: 4.40 [0.46] vs 3.61 [0.53], P < .001). Only years of hospital experience and NICU site were significantly associated with Current Practice and Necessary Practice total scores. IMPLICATIONS FOR PRACTICE: Ongoing assessment of the perceptions of NICU healthcare professionals regarding their current practice and beliefs about what is necessary for the delivery of high-quality family-centered care can inform NICU education, quality improvement, and maintenance of family-centered care during the COVID-19 pandemic. IMPLICATIONS FOR RESEARCH: Further research is needed to identify additional factors that predict family-centered care perceptions and behaviors.

Double lock of a potent human therapeutic monoclonal antibody against SARS-CoV-2.

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10 times the effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to the ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the receptor binding domain, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

University Students' Perceived Peer Support and Experienced Depressive Symptoms during the COVID-19 Pandemic: The Mediating Role of Emotional Well-Being.

The coronavirus (COVID-19) pandemic has adversely affected individuals' mental health. Social isolation as a result of social distancing during the pandemic potentially affects the associations among perceived available peer support, emotional well-being, and depression in university students. The present study examined the associations among university students' perceived available peer support, emotional well-being (as indicated negatively by loneliness and negative affects and positively by positive affects and hope), and depressive symptoms. During the third wave of the COVID-19 outbreak in July, 2020, 255 students at a public university in Hong Kong participated in an online-based survey that assessed their perceived available peer support, emotional well-being, and depressive symptoms. Results showed that perceived available peer support negatively contributed to depressive symptoms; both negative and positive indicators of emotional well-being mediated the association between perceived available peer support and depressive symptoms. Our results also suggested that university students showed signs of elevated depressive symptoms during the pandemic. Thus, our study advanced the theoretical understanding of university students' mental health in the time of a global pandemic. Our study also highlighted the practical needs for preventive efforts and accessible care to support the psychological and emotional needs of young people during the COVID-19 pandemic.