Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.

Expedited editorial decision in COVID-19 pandemic.

The COVID-19 pandemic and its resultant lockdowns have interrupted the way scientists live and work. This nevertheless caused an unforeseen impact of COVID-19: the pandemic substantially increased editorial speed. Here, we causally identify the impact of the pandemic on the editorial decision time, based on a quasi-experimental regression discontinuity (RD) design that compares (N = 339,199) papers submitted in the lead-up to and aftermath of the COVID-19 pandemic. We find that editors make acceptance decisions significantly quicker after the pandemic, reducing the editorial decision time of revised papers by 8.9 days on average. The pandemic, however, has unequal impacts on editors. The results reveal a larger reduction in editorial decision time for editors of high-tier journals, in the field of social science, or with busy work schedules. Finally, our findings also allude to the potential for the increase of editorial speed, and will stimulate policy changes in scientific enterprises that strive for accelerated publishing.

Organic Leadership-Implicit Followership Interaction: Relations among Trust in Supervisor, Active Followership and OCB

Due to the impact of COVID-19, a large number of employees of organizations around the world have been forced to work remotely from home starting in 2020. As a result, leaders and followers face new communication and interaction challenges. If an enterprise is to be successful in the new wave of economic development, it must embrace the role of employee followers. However, there is currently no relevant research. Therefore, the purpose of this study is to analyze the interaction between organic leadership and implicit followers from the perspective of followers who are working remotely and further analyze their relationship with trust in their supervisor, organizational citizenship behavior, and active followership. Using the method of questionnaire measurement, multigroup analysis and ANCOVA and PLS-SEM analysis found the following. First, difference in leadership styles (IV) and implicit followers (IV) had significant effects on employees' trust in supervisor (DV), organizational citizenship behavior (DV), and active followers (DV). Secondly, the influence of the leaders' styles (IV) on employees' trust in supervisor (DV), organizational citizenship behavior (DV), and active followership (DV) was significantly affected only when IFTs were anti-prototypical traits. Finally, organizational citizenship behavior (Med) had an indirect effect between trust in supervisor (DV) and active followership (DV). This article not only fills the gaps in the literature related to leaders and followers, but also provides analytical evidence and new thinking which will enable companies to propose management strategies more effectively for employees working remotely in the face of the impact of the epidemic.

Indoor thermal comfort in a rural dwelling in southwest China.

Recently, indoor thermal comfort has received more scholarly attention than ever due to the COVID-19 pandemic and global warming. However, most studies on indoor thermal comfort in China concentrated on urban buildings in the east and north. The indoor thermal comfort of rural dwellers in southwest China is insufficiently investigated. Hence, this study assesses residents' indoor thermal comfort in a rural dwelling in Linshui, obtains the thermal neutral temperature of the rural area, and analyzes the thermal adaptation behavior of rural dwellers. The results reveal that the thermal neutral temperature of rural dwellers is 29.33°C (operative temperature), higher than that presented in previous studies based on the same climate region. Indoor thermal conditions in rural dwellings are relatively harsh, but various thermal adaptation behavior of rural dwellers significantly improve their ability to withstand the harsh conditions. When people live in an environment with a (relatively) constant climate parameter (e.g., humidity), their perception of that parameter seems compromised. Most rural dwellers are unwilling to use cooling equipment with high energy consumption. Therefore, more passive cooling measures are recommended in the design and renovation of rural dwellings.

Effect of miR-221-3p targeting TIMP-2 on proliferation and apoptosis of vascular smooth muscle cells in abdominal aortic aneurysm

Objective: To investigate the effects of miR-221-3p on the proliferation and apoptosis of vascular smooth muscle cells (VSMC) in abdominal aortic aneurysm (AAA) by targeting tissue inhibitor of metalloproteinase- 2 (TIMP-2).

Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape.

Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses on apo Omicron spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The Omicron spike preferentially adopts the one-RBD-up conformation both before and after ACE2 binding, which is in sharp contrast to the orchestrated conformational changes to create more up-RBDs upon ACE2 binding as observed in the prototype and other four variants of concern (VOCs). Furthermore, we found that S371L, S373P and S375F substitutions enhance the stability of the one-RBD-up conformation to prevent exposing more up-RBDs triggered by ACE2 binding. The increased stability of the one-RBD-up conformation restricts the accessibility of S304 NAb, which targets a cryptic epitope in the closed conformation, thus facilitating the immune evasion by Omicron. These results expand our understanding of Omicron spike's conformation, receptor binding and antibody evasion mechanism.

Infectious kinetics of novel Coronavirus pneumonia (COVID-19)

Corona Virus Disease 2019 (COVID-IQ) occurred as new pneumonia of unknown cause at the end of 2019 and outbroke in the next two months in Wuhan, Hubei Province, China. Scientific and effective understanding of epidemic development is essential for the prevention and control. In this paper, a segmented Logistic model was built to describe confirmed cases, deaths and cured cases of COVID-19 based on the official data from National and Local Health Commissions. It is estimated that the total number of confirmed cases nationwide will reach 81,370 to 102,800 and the total number of deaths will reach 3,177 to 3, 960. with final mortality rate of 3.9%. All confirmed cases nationwide (exclude deaths) were expected to be cured by May 7, 2020 under current medical conditions and diagnostic criteria. The model can fit and forecast the trend of COVID-19 epidemics at two stages and provide scientific basis for epidemic prevention and control.

Advanced Functions Embedded in the Second Version of Database, Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2.

The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2 (GESS v2 https://shiny.ph.iu.edu/GESS_v2/) is an updated version of GESS, which has offered a handy query platform to analyze single-nucleotide variants (SNVs) on millions of high coverages and high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complete genomes provided by the Global Initiative on Sharing Avian Influenza Data (GISAID). Including the tools in the first version, the GESS v2 is embedded with new functions, which allow users to search SNVs, given the viral nucleotide or amino acid sequence. The GESS v2 helps users to identify SNVs or SARS-CoV-2 lineages enriched in countries of user's interest and show the migration path of a selected lineage on a world map during specific time periods chosen by the users. In addition, the GESS v2 can recognize the dynamic variations of newly emerging SNVs in each month to help users monitor SNVs, which will potentially become dominant soon. More importantly, multiple sets of analyzed results about SNVs can be downloaded directly from the GESS v2 by which users can conduct their own independent research. With these significant updates, the GESS v2 will continue to serve as a public open platform for researchers to explore SARS-CoV-2 evolutionary patterns from the perspectives of the prevalence and impact of SNVs.

Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

Innovation to Immune: Empirical Evidence From COVID-19 Focused Enterprise Surveys

The recent COVID-19 crisis caught many by surprise. Yet some firms were better prepared to weather the downturn than others. Using a comprehensive data set that observes over 15,000 firms in 27 countries, including several developing countries, shortly before and after the pandemic, we document that pre-crisis innovation affected firm’s survival odds and performance thereafter. The results show that innovative firms are less likely to close and perform better than non-innovators during the pandemic crisis. Innovative firms are also more optimistic about the future than non-innovators. Our results further indicate that firm’s adaptability mediates the relationship between innovation and survival outcomes. The study finding shows that innovative firms are more likely to introduce new products, remote work arrangements, increase delivery, pivoting, and online activities than non-innovators during the pandemic crisis.

What drives credit expansion Worldwide?——An empirical investigation with long-term cross-country panel data

This paper examines a broad range of driving factors of credit expansion using long-term cross-country panel data from 1994 to 2018 and the System GMM method. We discuss the role of macroeconomic fundamentals in explaining credit expansion by examining five categories of explanatory variables. Some structural patterns of weak linkages of credit expansion with macroeconomic fundamentals are identified. We further explore the possible causes that follow the theoretical logic of risk-taking in the private and public sectors. Controlling for the influence of macroeconomic fundamentals, we find the effects of various financial system characteristics, such as institutional features of the financial system, financial institutions' performance, asset markets booms, and macroeconomic and financial regulatory environment, on inducing credit expansion over the needs supported by macroeconomic fundamentals. Our study provides strong implications on regulatory policies on the rising credit during the COVID-19 Pandemic.

Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.

CIDO-COVID-19: An Ontology for COVID-19 Based on CIDO.

To realize integration, organization and reusability of knowledge related to COVID-19, an ontology for COVID-19 (CIDO-COVID-19) was constructed which extended the Coronavirus Infectious Disease Ontology (CIDO) by adding terms of COVID-19 related to symptoms, prevention, drugs and clinical domains. First, terms from the existing ontologies, literature, clinical guidelines and other resources about COVID-19 were merged. Then, the Stanford seven-step approach was used to define and organize the acquired terms. Finally, the CIDO-COVID-19 was built on basis of the terms mentioned above using Protégé. The CIDO-COVID-19 is a more comprehensive ontology for COVID-19, covering multiple areas in the domain of COVID-19, including disease, diagnosis, etiology, virus, transmission, symptom, treatment, drug and prevention.Clinical Relevance- The CIDO-COVID-19 covers multiple areas related to COVID-19, including diseases, diagnosis, etiology, virus, transmission, symptoms, treatment, drugs, prevention. Compared with the CIDO, it is expanded to cover drugs, prevention, and clinical domain. The definition of terms in CIDO-COVID-19 refers to biomedical ontologies, Clinical glossaries and clinical guidelines for COVID-19, which can provide clinicians with standard terminology in the clinical domain.

Exploring the perceptions of the educational environment in online acupuncture learning during the COVID-19 pandemic.

OBJECTIVE: Students have had to adapt to a "new normal" of online education at home during the COVID-19 pandemic. This poses a considerable challenge to the conduct of online acupuncture courses. Here, we provide our experience and guidance for conducting an online experimental acupuncture course during the COVID-19 pandemic. We aimed to compare the different perceptions of undergraduates to the educational environment between online and face-to-face learning approaches. METHODS: This study included senior undergraduates majoring in acupuncture during the academic years 2015 (face-to-face) and 2020 (online only) for the Experimental Acupuncture course. A survey was conducted at the end of this course. The Dundee Ready Educational Environment Measure (DREEM) questionnaire was used to assess students' perceptions. The results of students' responses to online learning were compared with those assessed for face-to-face learning. RESULTS: In total, 56/70 (80%) students in 2015 and 49/54 (91%) students in 2020 completed the questionnaire, respectively. Total DREEM scores were higher in the online learning group than in the face-to-face learning group (160.3 ± 21.9 vs 147.6 ± 17.9, p = 0.007), with improved students' perceptions on four out of five dimensions (social self-perception, learning, atmosphere and academic self-perception). The positive aspects of their online learning experience included the acquisition of new knowledge and skills. The significant limitations of this course included the lack of practical classes. CONCLUSION: Students' perceptions regarding the Experimental Acupuncture program were satisfactory for both online and face-to-face learning approaches, but even better with online learning. Online learning may be encouraged in traditional Chinese medicine (TCM) education. However, a combination of face-to-face and online methods is likely to be required to maximize the benefits. We hope that our online Experimental Acupuncture program practices may assist in the development of online curricula for acupuncture during the COVID-19 pandemic.

Updated SARS-CoV-2 single nucleotide variants and mortality association.

By analyzing newly collected SARS-CoV-2 genomes and comparing them with our previous study about SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found that the SNV clustering had changed remarkably since June 2020. Apart from that the group of SNVs became dominant, which is represented by two nonsynonymous mutations A23403G (S:D614G) and C14408T (ORF1ab:P4715L), a few emerging groups of SNVs were recognized with sharply increased monthly incidence ratios of up to 70% in November 2020. Further investigation revealed sets of SNVs specific to patients' ages and/or gender, or strongly associated with mortality. Our logistic regression model explored features contributing to mortality status, including three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male gender. The protein structure analysis indicated that the emerging subgroups of nonsynonymous SNVs and the mortality-related ones were located on the protein surface area. The clashes in protein structure introduced by these mutations might in turn affect the viral pathogenesis through the alteration of protein conformation, leading to a difference in transmission and virulence. Particularly, we explored the fact that nonsynonymous SNVs tended to occur in intrinsic disordered regions of Spike and ORF1ab to significantly increase hydrophobicity, suggesting a potential role in the change of protein folding related to immune evasion.

Cover Image, Volume 93, Number 12, December 2021

Front Cover Caption: The cover image is based on the Research Article Updated SARS-CoV-2 single nucleotide variants and mortality association by Shuyi Fang et al., https://doi.org/10.1002/jmv.27191.

Psychological Distress and Trust in University Management Among International Students During the COVID-19 Pandemic.

Since the end of 2019, the outbreak of the COVID-19 pandemic has engendered widespread fear and anxiety across China. Nearly half a million international students pursuing their studies in Chinese universities have also been exposed to the psychological distress triggered by the unfolding crisis. In addition to government and medical institutions' efforts, universities have also endeavored to mitigate concerns among these students under quarantine on campus by providing reliable information as well as medical, monetary, and emotional support. In this study, international students' trust in university management teams and its role in remediating their anxieties were evaluated using an online survey conducted after 10 days of the lockdown of Wuhan, China. The empirical analysis incorporates quantitative data from 180 international students. Ordinary least squares regression and probit regression were used in the analysis with the non-robust and robust models. The study found students' perception of trust in university management to be negatively associated with their anxiety levels. Additionally, having trust in university management was found to positively influence students' commitment to the self-quarantine guidelines. These results reinforce the important role of universities and their relationship with international students during public health emergencies.

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19.

SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between SARS-CoV-2 and nasopharyngeal microbiota, and the association with metabolome has not been well characterized. Here, metabolomic analysis of blood, urine, and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients, and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19. Results showed lactic acid, l-proline, and chlorogenic acid methyl ester (CME) were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones. Nasopharyngeal commensal bacteria including Gemella morbillorum, Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients, while Prevotella histicola, Streptococcus sanguinis, and Veillonella dispar were relatively increased. The abundance of G. haemolysans and L. hofstadii were significantly positively associated with serum CME, which might be an anti-SARS-CoV-2 bacterial metabolite. This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility. The findings were based on a very limited number of patients enrolled in this study; a larger size of cohort will be appreciated for further investigation.

Extracorporeal membrane oxygenation for coronavirus disease 2019-associated acute respiratory distress syndrome: Report of two cases and review of the literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2, is a worldwide pandemic. Some COVID-19 patients develop severe acute respiratory distress syndrome and progress to respiratory failure. In such cases, extracorporeal membrane oxygenation (ECMO) treatment is a necessary life-saving procedure. CASE SUMMARY: Two special COVID-19 cases-one full-term pregnant woman and one elderly (72-year-old) man-were treated by veno-venous (VV)-ECMO in the Second People's Hospital of Zhongshan, Zhongshan City, Guangdong Province, China. Both patients had developed refractory hypoxemia shortly after hospital admission, despite conventional support, and were therefore managed by VV-ECMO. Although both experienced multiple ECMO-related complications on top of the COVID-19 disease, their conditions improved gradually. Both patients were weaned successfully from the ECMO therapy. At the time of writing of this report, the woman has recovered completely and been discharged from hospital to home; the man remains on mechanical ventilation, due to respiratory muscle weakness and suspected lung fibrosis. As ECMO itself is associated with various complications, it is very important to understand and treat these complications to achieve optimal outcome. CONCLUSION: VV-ECMO can provide sufficient gas exchange for COVID-19 patients with acute respiratory distress syndrome. However, it is crucial to understand and treat ECMO-related complications.

GESS: a database of global evaluation of SARS-CoV-2/hCoV-19 sequences.

The COVID-19 outbreak has become a global emergency since December 2019. Analysis of SARS-CoV-2 sequences can uncover single nucleotide variants (SNVs) and corresponding evolution patterns. The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences (GESS, https://wan-bioinfo.shinyapps.io/GESS/) is a resource to provide comprehensive analysis results based on tens of thousands of high-coverage and high-quality SARS-CoV-2 complete genomes. The database allows user to browse, search and download SNVs at any individual or multiple SARS-CoV-2 genomic positions, or within a chosen genomic region or protein, or in certain country/area of interest. GESS reveals geographical distributions of SNVs around the world and across the states of USA, while exhibiting time-dependent patterns for SNV occurrences which reflect development of SARS-CoV-2 genomes. For each month, the top 100 SNVs that were firstly identified world-widely can be retrieved. GESS also explores SNVs occurring simultaneously with specific SNVs of user's interests. Furthermore, the database can be of great help to calibrate mutation rates and identify conserved genome regions. Taken together, GESS is a powerful resource and tool to monitor SARS-CoV-2 migration and evolution according to featured genomic variations. It provides potential directive information for prevalence prediction, related public health policy making, and vaccine designs.