From concept to delivery: a yeast-expressed recombinant protein-based COVID-19 vaccine technology suitable for global access.

INTRODUCTION: The development of a yeast-expressed recombinant protein-based vaccine technology co-developed with LMIC vaccine producers and suitable as a COVID-19 vaccine for global access is described. The proof-of-concept for developing a SARS-CoV-2 spike protein receptor-binding domain (RBD) antigen as a yeast-derived recombinant protein vaccine technology is described. AREAS COVERED: Genetic Engineering: The strategy is presented for the design and genetic modification used during cloning and expression in the yeast system. Process and Assay Development: A summary is presented of how a scalable, reproducible, and robust production process for the recombinant protein COVID-19 vaccine antigen was developed. Formulation and Pre-clinical Strategy: We report on the pre-clinical and formulation strategy used for the proof-of-concept evaluation of the SARS-CoV-2 RBD vaccine antigen. Technology Transfer and Partnerships: The process used for the technology transfer and co-development with LMIC vaccine producers is described. Clinical Development and Delivery: The approach used by LMIC developers to establish the industrial process, clinical development, and deployment is described. EXPERT OPINION: Highlighted is an alternative model for developing new vaccines for emerging infectious diseases of pandemic importance starting with an academic institution directly transferring their technology to LMIC vaccine producers without the involvement of multinational pharma companies.

The moderating effect of leadership empowerment on relational capital and firms' innovation performance in the entrepreneurial ecosystem: Evidence from China

PurposeThis study aims to fill the research gap on the moderating effect of leadership empowerment on the relationship between relational capital and firms' innovation performance in the entrepreneurial ecosystem by addressing the following research questions: (1) How do different types of relational capital positively or negatively affect firms' innovation performance in China? (2) Does leadership empowerment play a moderating role in the above relationship?Design/methodology/approachUsing data derived from the firms distributed in eastern, central and western China, the authors study the impact of relational capital, one of the dimensions of intellectual capital, on firms' innovation performance in the entrepreneurial ecosystem. Based on firms' operation process regarding the relationships with their external stakeholders, the authors divided relational capital into three aspects: trust, reciprocity and transparency. Furthermore, leadership empowerment is taken as the moderating variable in the above theoretical relationship.FindingsThere is significant evidence that trust, reciprocity and transparency have positive impact on firms' innovation performance. Leadership empowerment positively moderates the impact of trust and reciprocity on innovation performance. However, there is no significant moderating effect of leadership empowerment on the relationship between transparency and innovation performance.Originality/valueIn the era of the knowledge economy, the entrepreneurial ecosystem is a critical foundation for firms to improve their innovation capacity and performance, and intellectual capital is one of the most imperative drivers in terms of firms' innovation performance. Nevertheless, few studies have investigated thoroughly concerning the relationships among the entrepreneurial ecosystem, intellectual capital and innovation performance. As this study explores the relationships among the above three factors, it may have profound theoretical and practical significance for firms to extent external relationship networks, improve their innovation performance and strengthen their core competencies, which is of great significance to facilitate the construction of entrepreneurial ecosystem.

Association of Social Isolation and Loneliness With Incident Heart Failure in a Population-Based Cohort Study.

BACKGROUND: Social isolation and loneliness have emerged as important risk factors for cardiovascular diseases, particularly during the coronavirus disease pandemic. However, it is unclear whether social isolation and loneliness had independent and joint associations with incident heart failure (HF). OBJECTIVES: This study sought to examine the association of social isolation, loneliness, and their combination with incident HF. METHODS: The UK Biobank study is a population-based cohort study. Social isolation and loneliness were assessed using self-reported questionnaires. HF cases were identified by linking hospital records and death registries. The weighted polygenic risk score associated with HF was calculated. RESULTS: Among the 464,773 participants (mean age: 56.5 ± 8.1 years, 45.3% male), 12,898 incident HF cases were documented during a median follow-up of 12.3 years. Social isolation (most vs least: adjusted HR: 1.17; 95% CI:1.11-1.23) and loneliness (yes vs no: adjusted HR: 1.19; 95% CI: 1.11-1.27) were significantly associated with an increased risk of incident HF. The association between an elevated risk of HF and social isolation was modified by loneliness (Pinteraction = 0.034). A gradient of association between social isolation and the risk of incident HF was found only among individuals without loneliness (Ptrend < 0.001), but not among those with loneliness (Ptrend = 0.829). These associations were independent of the genetic risk of HF. CONCLUSIONS: Social isolation and loneliness were independently associated with a higher likelihood of incident HF regardless of genetic risk. The association between social isolation and incident HF was potentially modified by loneliness status.

The impact of the COVID-19 pandemic on the care of pulmonary hypertension patients outside the Hubei province in China.

The Coronavirus disease 2019 (COVID-19) pandemic has severely affected the lives of people around the world, especially some patients with severe chronic diseases. This study aims to evaluate the impact of the COVID-19 outbreak from December 2019 to April 2020 on treating patients with PH. A questionnaire regarding the medical condition of PH patients during the COVID-19 pandemic was designed by PH diagnostic experts in The First Affiliated Hospital of Guangzhou Medical University, China Respiratory Center. One hundred and fifty-six subjects with PH from non-Hubei regions in China were invited to participate in this survey online. 63.4% (n = 99) of them had difficulty seeing a doctor, and the main reason was fear of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the hospital. Medical treatment was affected in 25% (n = 39) of patients, and who lived in rural areas, and discontinued medical therapy for financial reasons were at a higher risk of medical treatment being affected. Patients who reduced nutrition, and had difficulty seeing a doctor were more likely to get deteriorated. During the epidemic, the hospitalization rate of PH patients was 33.33%. Patients with aggravated PH had a high risk of hospitalization (odds ratio [OR] = 2.844), while patients who visited a doctor during the epidemic reduced the risk of hospitalization (OR = 0.33). In conclusion, during the COVID-19 pandemic, PH patients had difficulty seeing a doctor, and their medical treatment was affected, even worsened, and increased the risk of hospitalization.

The impact of the COVID‐19 pandemic on the care of pulmonary hypertension patients outside the Hubei province in China

The Coronavirus disease 2019 (COVID‐19) pandemic has severely affected the lives of people around the world, especially some patients with severe chronic diseases. This study aims to evaluate the impact of the COVID‐19 outbreak from December 2019 to April 2020 on treating patients with PH. A questionnaire regarding the medical condition of PH patients during the COVID‐19 pandemic was designed by PH diagnostic experts in The First Affiliated Hospital of Guangzhou Medical University, China Respiratory Center. One hundred and fifty‐six subjects with PH from non‐Hubei regions in China were invited to participate in this survey online. 63.4% (n = 99) of them had difficulty seeing a doctor, and the main reason was fear of contracting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in the hospital. Medical treatment was affected in 25% (n = 39) of patients, and who lived in rural areas, and discontinued medical therapy for financial reasons were at a higher risk of medical treatment being affected. Patients who reduced nutrition, and had difficulty seeing a doctor were more likely to get deteriorated. During the epidemic, the hospitalization rate of PH patients was 33.33%. Patients with aggravated PH had a high risk of hospitalization (odds ratio [OR] = 2.844), while patients who visited a doctor during the epidemic reduced the risk of hospitalization (OR = 0.33). In conclusion, during the COVID‐19 pandemic, PH patients had difficulty seeing a doctor, and their medical treatment was affected, even worsened, and increased the risk of hospitalization.

Visibility, wind speed, and dew point temperature are important factors in SARS-CoV-2 transmissibility.

The aim of this study is to provide evidence for the influencing factors of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus mutation by determining the impact of geographical and meteorological factors on SARS-CoV-2 transmission, and the different impacts of SARS-CoV-2 variant strains. From January 20 to March 10, 2020, we collected a number of daily confirmed new cases and meteorological factors in all cities and regions in China and Italy affected by the Alpha "variants of concern" (VOC). We also collected the daily confirmed cases of the Delta VOC infection in China and Italy from May 21 to November 30, 2021. The relationships between daily meteorological data and daily verified new cases of SARS-CoV-2 transmission were then investigated using a general additive model (GAM) with a log link function and Poisson family. The results revealed that latitude was substantially connected with daily confirmed new instances of the Alpha VOC, while there was no such correlation with Delta VOC transmission. When visibility is greater than 7 m, the propagation of the Alpha and Delta VOCs in Italy and China can be controlled. Furthermore, greater temperatures and increased wind speed reduce the transmission of the Alpha and Delta VOCs. In conclusion, geographical and meteorological factors play an important role in SARS-CoV-2 transmissibility and should be considered in virus mitigation strategies.

The health and economic impact of constructing temporary field hospitals to meet the COVID-19 pandemic surge: Wuhan Leishenshan Hospital in China as a case study.

BACKGROUND: In response to the COVID-19 pandemic, two new temporary hospitals were constructed in record time in Wuhan, China, to help combat the fast-spreading virus in February 2020. Using the experience of one of the hospitals as a case study, we discuss the health and economic implications of this response strategy and its potential application in other countries. METHODS: This retrospective observational study analyzed health resource utilization and clinical outcomes data for 2011 inpatients diagnosed with COVID-19 and admitted to Leishenshan Hospital during its 67 days of operation from February 8th to April 14th, 2020. We used a top-down costing approach to estimate the total cost of treating patients at the Leishenshan Hospital, including capital cost for hospital construction, health personnel costs, and direct health care costs. We used a multivariate generalized linear model to examine risk factors associated with in-hospital deaths. RESULTS: During the 67 days of hospital operation, 19 medical teams comprising of 933 doctors and 2312 nurses were gradually transferred to Leishenshan Hospital from across China. Of the 2011 admissions, 4.5% used intensive care and 2.0% used ventilators. Overall median length of stay was 19 days, and 21 days for patients in the intensive care unit (ICU). The case fatality rate (CFR) was 2.3% overall, 41.8% in the ICU, and 0.4% in general ward (GW). CFRs were 55% and 50% among patients using non-invasive and invasive ventilators, respectively. The mean total cost and direct health care cost were CNY806 997 (US$114 793) and CNY16 087 (US$2288), respectively. Patients admitted to the ICU had much higher direct health care costs, on average, compared to those in the GW (CNY150 415 vs CNY9720, or US$21 396 vs US$1383). The mean direct health care cost per patient with severe or critical diseases was more than five times higher than those with mild or moderate diseases (CNY45 191 vs CNY8838, or US$6428 vs US$1257). Older age, having comorbidities, and critical disease were associated with higher risks of death from COVID-19. Lower health worker to patient ratio (<2.6) was not associated with in-hospital death. CONCLUSION: An adequate health workforce were mobilized and deployed to a new temporary hospital. The Leishenshan Hospital increased access to care during the surge in COVID-19 infections, facilitated timely treatment, and transferred COVID-19 patients between GWs and ICUs within the hospital, all of which are potential contributors to lowering the CFR. Patients in the ICU experienced a much higher CFR and a greater burden of health care cost than those in GW. Our results have important implications for other countries interested in constructing temporary emergency hospitals, such as the need for adequate infrastructure capacities and financial support, centralized strategies to mobilize health workforce and to provide respiratory protective devices, and improvement in access to health care.

Yeast-expressed recombinant SARS-CoV-2 receptor binding domain RBD203-N1 as a COVID-19 protein vaccine candidate.

SARS-CoV-2 protein subunit vaccines are currently being evaluated by multiple manufacturers to address the global vaccine equity gap, and need for low-cost, easy to scale, safe, and effective COVID-19 vaccines. In this paper, we report on the generation of the receptor-binding domain RBD203-N1 yeast expression construct, which produces a recombinant protein capable of eliciting a robust immune response and protection in mice against SARS-CoV-2 challenge infections. The RBD203-N1 antigen was expressed in the yeast Pichia pastoris X33. After fermentation at the 5 L scale, the protein was purified by hydrophobic interaction chromatography followed by anion exchange chromatography. The purified protein was characterized biophysically and biochemically, and after its formulation, the immunogenicity was evaluated in mice. Sera were evaluated for their efficacy using a SARS-CoV-2 pseudovirus assay. The RBD203-N1 protein was expressed with a yield of 492.9 ± 3.0 mg/L of fermentation supernatant. A two-step purification process produced a >96% pure protein with a recovery rate of 55 ± 3% (total yield of purified protein: 270.5 ± 13.2 mg/L fermentation supernatant). The protein was characterized to be a homogeneous monomer that showed a well-defined secondary structure, was thermally stable, antigenic, and when adjuvanted on Alhydrogel in the presence of CpG it was immunogenic and induced high levels of neutralizing antibodies against SARS-CoV-2 pseudovirus. The characteristics of the RBD203-N1 protein-based vaccine show that this candidate is another well suited RBD-based construct for technology transfer to manufacturing entities and feasibility of transition into the clinic to evaluate its immunogenicity and safety in humans.

A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity.

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes MHC complex and ApoE, respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including type I interferon receptor binding and SARS coronavirus and innate immunity. We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.

Field-based evidence of changes in household PM2.5 and exposure during the 2020 national quarantine in China

Air pollution exposure depends not only on outdoor but also on indoor air quality and human activities. The outbreak of coronavirus in 2019 occurred close to the Spring Festival in China, when many rural-to-urban workers moved to their hometowns, resulting in increased household (HH) consumption of solid fuels for space heating in the rural north. In this study, field measurements of HH PM2.5 (particulate matter with an aerodynamic size ⩽2.5 μm) from a rural village were performed to evaluate changes in indoor, outdoor, and total exposure during the quarantine. Both indoor and outdoor PM2.5 were, as expected, higher during the heating period than during the non-heating period, resulting in much more exposure during the heating season. Indoor exposure accounted for up to 87% and 95% of the total PM2.5 exposure during the non-heating and heating periods, respectively. The contributions of indoor exposure associated with internal sources were 46% and 66%, respectively. Indoor coal combustion resulted in an increment of about 62 ± 12 μg m−3 in indoor PM2.5 exposure. Due to the quarantine, the indoor-originated PM2.5 exposure increased by 4 μg m−3 compared to that during the heating period before the lockdown. In comparison with the exposure before the quarantine during the heating period, the outdoor exposure decreased by 5 μg m−3 during the quarantine, which was mainly attributable to much less time spent outdoors, although the outdoor PM2.5 levels increased from 86 ± 49 μg m−3 to 104 ± 85 μg m−3. However, the overall exposure increased by 13 μg m−3 during the quarantine, resulting from the changes in outdoor exposure (−5 μg m−3), outdoor-originated indoor PM2.5 exposure (+9 μg m−3), PM2.5 from indoor sources before the quarantine (+5 μg m−3), and quarantine-induced indoor PM2.5 increments (+4 μg m−3). The increase in air pollution exposure during quarantine deepened concerns about the issue of HH air pollution and the clean HH energy transition actions required to eliminate traditional solid fuels.

Association Between Future Orientation and Anxiety in University Students During COVID-19 Outbreak: The Chain Mediating Role of Optimization in Primary-Secondary Control and Resilience.

The unfamiliar and menacing epidemic has undoubtedly increased the anxiety of students. Therefore, the strategies to reduce anxiety are urgently required. The present study principally investigated a protective mechanism of future orientation in anxiety during the low-risk period of COVID-19 outbreak. The study was conducted in 528 non-infected students (range = 16-24 years) recruited from five universities in China. The participants completed questionnaires between January 22, 2021, and January 24, 2021. Chain intermediary analyses were performed after controlling for gender and age. Results indicated that future orientation lowers anxiety through (a) optimization in primary and secondary control, (b) resilience, and (c) chain mediating path of optimization in primary and secondary control coupled with resilience. We investigated how individuals deal with risk factors after encountering adversity and how their psychological flexibility stimulates and promotes them to achieve a well-adapted developmental state. This study provided reference suggestions on reducing anxiety levels during an emergency.

Mobile isolation wards in a fever clinic: a novel operation model during the COVID-19 pandemic.

A fever clinic within a hospital plays a vital role in pandemic control because it serves as an outpost for pandemic discovery, monitoring and handling. As the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan was gradually brought under control, the fever clinic in the West Campus of Wuhan Union Hospital introduced a new model for construction and management of temporary mobile isolation wards. A traditional battlefield hospital model was combined with pandemic control regulations, to build a complex of mobile isolation wards that used adaptive design and construction for medical operational, medical waste management and water drainage systems. The mobile isolation wards allowed for the sharing of medical resources with the fever clinic. This increased the capacity and efficiency of receiving, screening, triaging and isolation and observation of patients with fever. The innovative mobile isolation wards also controlled new sudden outbreaks of COVID-19. We document the adaptive design and construction model of the novel complex of mobile isolation wards and explain its characteristics, functions and use.

Increased air pollution exposure among the Chinese population during the national quarantine in 2020.

The COVID-19 quarantine in China is thought to have reduced ambient air pollution. The overall exposure of the population also depends, however, on indoor air quality and human mobility and activities. Here, by integrating real-time mobility data and a questionnaire survey on time-activity patterns during the pandemic, we show that despite a decrease in ambient PM2.5 during the quarantine, the total population-weighted exposure to PM2.5 considering both indoor and outdoor environments increased by 5.7 µg m-3 (95% confidence interval, 1.2-11.0 µg m-3). The increase in population-weighted exposure was mainly driven by a nationwide urban-to-rural population migration before the Spring Festival coupled with the freezing of the migration backward due to the quarantine, which increased household energy consumption and the fraction of people exposed to rural household air pollution indoors. Our analysis reveals an increased inequality of air pollution exposure during the quarantine and highlights the importance of household air pollution for population health in China.