Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Research on the Design of Virtual Reality Online Education Information Presentation Based on Multi-Sensory Cognition

The popularity of the online teaching model increased during the COVID-19, and virtual reality online education is now firmly established as a future trend in educational growth. Human–computer interaction and collaboration between virtual models and physical entities, as well as virtual multi-sensory cognition, have become the focus of research in the field of online education. In this paper, we analyze the mapping form of teaching information and cue information on users' cognition through an experimental system and investigate the effects of the presentation form of online virtual teaching information, the length of the material, users' memory of the information, and the presentation form of information cues on users' cognitive performance. The experimental results show that different instructional information and cue presentation designs have significant effects on users' learning performance, with relatively longer instructional content being more effective and users being more likely to mechanically remember the learning materials. By studying the impact of multi-sensory information presentation on users' cognition, the output design of instructional information can be optimized, cognitive resources can be reasonably allocated, and learning effectiveness can be ensured, which is of great significance for virtual education research in digital twins.

Adjuvant-Free COVID-19 Vaccine with Glycoprotein Antigen Oxidized by Periodate Rapidly Elicits Potent Immune Responses.

Modification of antigens to improve their immunogenicity represents a promising direction for the development of protein vaccine. Here, we designed facilely prepared adjuvant-free vaccines in which the N-glycan of SARS-CoV-2 receptor-binding domain (RBD) glycoprotein was oxidized by sodium periodate. This strategy only minimally modifies the glycans and does not interfere with the epitope peptides. The RBD glycoprotein oxidized by high concentrations of periodate (RBDHO) significantly enhanced antigen uptake mediated by scavenger receptors and promoted the activation of antigen-presenting cells. Without any external adjuvant, two doses of RBDHO elicited 324- and 27-fold increases in IgG antibody titers and neutralizing antibody titers, respectively, compared to the unmodified RBD antigen. Meanwhile, the RBDHO vaccine could cross-neutralize all of the SARS-CoV-2 variants of concern. In addition, RBDHO effectively enhanced cellular immune responses. This study provides a new insight for the development of adjuvant-free protein vaccines.

Clinical characteristics of pediatric cases infected with the SARS-CoV-2 Omicron variant in a tertiary children's medical center in Shanghai, China.

BACKGROUND: The number of pediatric cases of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has increased. Here, we describe the clinical characteristics of children in a tertiary children's medical center in Shanghai. METHODS: A total of 676 pediatric coronavirus disease 2019 (COVID-19) cases caused by the Omicron variant who were admitted to the Shanghai Children's Medical Center from March 28 to April 30, 2022 were enrolled in this single-center, prospective, observational real-world study. Patient demographics and clinical characteristics, especially COVID-19 vaccine status, were assessed. RESULTS: Children of all ages appeared susceptible to the SARS-CoV-2 Omicron variant, with no significant difference between sexes. A high SARS-CoV-2 viral load upon admission was associated with leukocytopenia, neutropenia, and thrombocytopenia (P = 0.003, P = 0.021, and P = 0.017, respectively) but not with physical symptoms or radiographic chest abnormalities. Univariable linear regression models indicated that comorbidities (P = 0.001) were associated with a longer time until viral clearance, and increasing age (P < 0.001) and two doses of COVID-19 vaccine (P = 0.001) were associated with a shorter time to viral clearance. Multivariable analysis revealed an independent effect of comorbidities (P < 0.001) and age (P = 0.003). The interaction effect between age and comorbidity showed that the negative association between age and time to virus clearance remained significant only in patients without underlying diseases (P < 0.001). CONCLUSION: This study describes the clinical characteristics of children infected with the Omicron variant of SARS-CoV-2 and calls for additional studies to evaluate the effectiveness and safety of vaccination against COVID-19 in children.

Stress and depressive symptoms in university students in Hong Kong under the pandemic: Moderating effect of positive psychological attributes.

Introduction: There are very few studies examining the psychological well-being of university students in Hong Kong under the COVID-19 pandemic. Besides COVID-19-related stress, the "social event" in 2019-2020 has caused significant stress in young people. As such, we attempted to answer several research questions in this paper. First, what are the relationships between stresses (COVID-19 and "social event" related stresses) and psychological well-being indexed by depressive symptoms? Based on the stress and coping perspective, we predicted that there would be positive relationships between both types of stress and depression. Second, what are the relationships between different positive psychological factors (including life satisfaction, resilience and emotional management, flourishing, and beliefs about adversity) and depression? Based on different theoretical models of positive psychology, we hypothesized that negative relationships would exist between positive psychological factors and depressive symptoms. Third, do positive psychological attributes moderate the associations between stresses (COVID-19 and "social event" related stresses) and depressive symptoms? Based on the positive psychology literature, we hypothesized that positive psychological attributes would buffer the negative impact of stresses on depression. Methods: We recruited university students roughly one year after the first wave of the pandemic (N = 1,648) in early 2021. We used 25 items to measure COVID-19-related stress and "social event" related stress. For psychological well-being indexed by depressive symptoms, we used the "Centre for Epidemiologic Studies Depression Scale Revised (CESD-R)". For positive psychological attributes, we employed established measures of life satisfaction, resilience and emotional management, flourishing, and beliefs about adversity. Results: Regarding the relationship between stress and depression, we found positive relationships between both types of stress and depressive symptoms. As predicted, negative relationships existed between all positive psychological attributes and depressive symptoms. Besides, the positive psychological attributes significantly moderated the effects of stresses on depression, suggesting that these factors can reduce the negative impacts of stresses on depression. The present findings provide support for those models, highlighting the importance of positive psychological attributes as protective factors for university students' depression. Discussion: The findings of this study underscore the important role of positive psychological attributes in the stress-depression relationship in university students under the pandemic. The findings also generalize the positive youth development theory in the Chinese context. In terms of practice, university administrators and service providers should consider cultivating positive psychological attributes in university students with the purpose of promoting their psychological well-being.

Profiling Humoral Immunity After Mixing and Matching COVID-19 Vaccines Using SARS-CoV-2 Variant Protein Microarrays.

In November 2022, 68% of the population received at least one dose of COVID-19 vaccines. Owing to the ongoing mutations, especially for the variants of concern (VOCs), it is important to monitor the humoral immune responses after different vaccination strategies. In this study, we developed a SARS-CoV-2 variant protein microarray that contained the spike proteins from the VOCs, e.g., alpha, beta, gamma, delta, and omicron, to quantify the binding antibody and surrogate neutralizing antibody. Plasmas were collected after two doses of matching AZD1222 (AZx2), two doses of matching mRNA-1273 (Mx2), or mixing AZD1222 and mRNA-1273 (AZ+M). The results showed a significant decrease of surrogate neutralizing antibodies against the receptor-binding domain in all VOCs in AZx2 and Mx2 but not AZ+M. A similar but minor reduction pattern of surrogate neutralizing antibodies against the extracellular domain was observed. While Mx2 exhibited a higher surrogate neutralizing level against all VOCs compared with AZx2, AZ+M showed an even higher surrogate neutralizing level in gamma and omicron compared with Mx2. It is worth noting that the binding antibody displayed a low correlation to the surrogate neutralizing antibody (R-square 0.130-0.382). This study delivers insights into humoral immunities, SARS-CoV-2 mutations, and mixing and matching vaccine strategies, which may provide a more effective vaccine strategy especially in preventing omicron.

Takotsubo Syndrome Occurring after mRNA COVID-19 Vaccination in a Patient with Graves' Disease.

Cardiovascular events such as myocarditis following mRNA COVID-19 vaccination are increasing. We present a 67-year-old postmenopausal woman with Takotsubo Syndrome and Graves' disease after mRNA COVID-19 vaccination. She developed chest pain and shortness of breath one week after vaccination. An electrocardiogram revealed ST elevation in the precordial leads. Coronary angiography revealed the absence of obstructive coronary artery disease, and the left ventriculography showed a typical feature with apical ballooning. Laboratory workup showed the elevation of free T4 and thyrotropin receptor antibodies. It was presumed that Takotsubo Syndrome and Graves' disease were probably related to the COVID-19 mRNA vaccination. The patient was treated with low-dose bisoprolol, diuretics, carbimazole, and steroid and discharged uneventfully. The mRNA COVID-19 vaccination is still safe and effective to defend against COVID-19 pandemic. However, clinicians should be aware of the possible cardiovascular adverse events other than myocarditis following vaccination.

pH-Sensitive and Biodegradable Mn3(PO4)2·3H2O Nanoparticles as an Adjuvant of Protein-Based Bivalent COVID-19 Vaccine to Induce Potent and Broad-Spectrum Immunity.

Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of great significance to enhance vaccine efficacy. In this work, we prepared a long-term stable, pH-sensitive, and biodegradable Mn3(PO4)2·3H2O nanoparticle (nano-MnP) by simply mixing MnCl2/NaH2PO4/Na2HPO4 solution for the first time and employed it as an immune stimulant in the bivalent COVID-19 protein vaccine comprised of wild-type S1 (S1-WT) and Omicron S1 (S1-Omicron) proteins as antigens to elicit a broad-spectrum immunity. The biological experiments indicated that the nano-MnP could effectively activate antigen-presenting cells through the cGAS-STING pathway. Compared with the conventional Alum-adjuvanted group, the nano-MnP-adjuvanted bivalent vaccine elicited approximately 7- and 8-fold increases in IgG antibody titers and antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera of the nano-MnP-adjuvanted group could effectively cross-neutralize the SARS-CoV-2 and its five variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron, demonstrating that this bivalent vaccine based on S1-WT and S1-Omicron proteins is an effective vaccine design strategy to induce broad-spectrum immune responses. Collectively, this nano-MnP material may provide a novel and efficient adjuvant platform for various prophylactic and therapeutic vaccines and provide insights for the development of the next-generation manganese adjuvant.

Novel sialoglycan linkage for constructing adjuvant-protein conjugate as potent vaccine for COVID-19.

Self-adjuvanting protein vaccines have been proved to be highly immunogenic with efficient codelivery of adjuvant and antigen. Current protein vaccines with built-in adjuvants are all modified at the peptide backbone of antigen protein, which could not achieve minor epitope interference and adjuvant multivalency at the same time. Herein, we developed a new conjugate strategy to construct effective adjuvant-protein vaccine with adjuvant cluster effect and minimal epitope interference. The toll-like receptor 7 agonist (TLR7a) is covalently conjugated on the terminal sialoglycans of SARS-CoV-2-S1 protein, leading to intracellular release of the small-molecule stimulators with greatly reduced risks of systemic toxicity. The resulting TLR7a-S1 conjugate elicited strong activation of immune cells in vitro, and potent antibody and cellular responses with a significantly enhanced Th1-bias in vivo. TLR7a-S1-induced antibody also effectively cross-neutralized all variants of concern. This sialoglycoconjugation approach to construct protein conjugate vaccines will have more applications to combat SARS-CoV-2 and other diseases.

Self-Adjuvanting Protein Vaccine Conjugated with a Novel Synthetic TLR4 Agonist on Virus-Like Liposome Induces Potent Immunity against SARS-CoV-2.

Exploring potent adjuvants and new vaccine strategies is crucial for the development of protein vaccines. In this work, we synthesized a new TLR4 agonist, structurally simplified lipid A analogue GAP112, as a potent built-in adjuvant to improve the immunogenicity of SARS-CoV-2 spike RBD protein. The new TLR4 agonist GAP112 was site-selectively conjugated on the N-terminus of RBD to construct an adjuvant-protein conjugate vaccine in a liposomal formulation. It is the first time that a TLR4 agonist is site-specifically and quantitatively conjugated to a protein antigen. Compared with an unconjugated mixture of GAP112/RBD, a two-dose immunization of the GAP112-RBD conjugate vaccine strongly activated innate immune cells, elicited a 223-fold increase in RBD-specific antibodies, and markedly enhanced T-cell responses. Antibodies induced by GAP112-RBD also effectively cross-neutralized SARS-CoV-2 variants (Delta/B.1.617.2 and Omicron/B.1.1.529). This conjugate strategy provides an effective method to greatly enhance the immunogenicity of antigen in protein vaccines against SARS-CoV-2 and other diseases.

Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.

Excessive Gaming and Online Energy-Drink Marketing Exposure Associated with Energy-Drink Consumption among Adolescents.

In this study, we examined excessive online gaming by adolescents and the resultant effects of their exposure to the online marketing of energy drinks and alcohol, and whether marketing literacy could serve as a mitigating factor. This cross-sectional study was conducted in 2020. Data were obtained from a sample of 2613 seventh-grade students from 30 middle schools in Taiwan. A self-administered questionnaire was conducted. The results showed that nearly 18% of the adolescent respondents had used energy drinks, while 75% reported seeing energy-drink advertisements on the internet in the past year. Multiple regression results indicated that factors such as being male, reporting excessive gaming, being exposed to higher levels of online energy-drink marketing, and reporting alcohol use were positively associated with energy-drink consumption. A higher level of online energy-drink marketing-affective literacy, however, was negatively associated with energy-drink consumption. In conclusion, factors that predicted energy-drink consumption among adolescents included excessive gaming and exposure to online energy-drink marketing, but marketing-affective literacy tended to lessen the impact of such advertising.

An electrochemiluminescence biosensor based on morphology controlled iridium complex nanomaterials for SARS-CoV-2 nucleocapsid protein detection

The morphology of electrochemiluminescence (ECL) emitters is closely related to ECL properties, thus the control of their morphology is greatly essential for ECL applications. Herein, a facile nanoprecipitation method was developed to realize controllable morphology of iridium complex nanomaterials by modulating the volume ratio of poly(styrene-co-maleicanhydride) (PSMA) to tris (2-phenylpyridine) iridium(Ⅲ) (Ir(ppy)3). Furthermore, ECL properties of iridium complex nanomaterials with different morphologies were explored through a series of experiments. Iridium complex nanoparticles (Ir NPs) with excellent ECL performance were selected as admirable ECL emitters to construct biosensors. Ir NPs served as the matrix to stepwise capture primary antibody, antigen of SARS-CoV-2 nucleocapsid protein (ncovNP) and secondary antibody bioconjugate coupled with dual quenchers and detection antibody. Taking advantage of the significant quenching effect of noradrenaline (NA) and gold nanoparticles (Au NPs) in the secondary antibody bioconjugate on ECL emission from Ir NPs, the developed ECL biosensor realized the sensitive detection of ncovNP and the detection limit was as low as 47 fg/mL. The integration of morphology-controlled iridium complex nanomaterials and dual quenchers NA and Au NPs provides a promising ECL platform.

Effort-reward imbalance and job strain index associated with health-related quality of life for civil servants in a national survey: the mediation effect of job support and over-commitment.

OBJECTIVES: Work-related stress (WRS) is significantly associated with health-related quality of life (HRQoL), but the amounts of evidence on differences of effort-reward imbalance (ERI) and job strain index (JSI) remain sparse and have limited generalizability. Therefore, we aimed to assess the association between ERI and JSI with HRQoL and assess the mediation effect of social support (JS) and over-commitment (OC) on this association in Taiwan's civil servants. MATERIAL AND METHODS: A cross-sectional national survey was given to registered civil servants in Taiwan - 20 046 civil servants from 647 institutions were enrolled using multistage stratified random cluster sampling. A web-questionnaire collected demographic information, job characteristics, and different indexes of ERI and job-control-demand-support (JCDS) models. Structural equation model (SEM) was used to examine the association between ERI and JSI with HRQoL, and the mediation effect of JS and OC on the associations. RESULTS: In the ERI model, ERI and OC were consistently negatively associated with the mental component score (MCS) (r = -0.46 and r = -0.37) and physical component score (PCS) (r = -0.45 and r = -0.34), which were higher than job demand (r = -0.28 and r = -0.22) and JSI (r = -0.38 and r = -0.29). Using hierarchical multiple regression analyses, ERI was significantly correlated with MCS and PCS, which was consistently higher than JSI. The ERI and JSI were significantly correlated with MCS (ß = -0.170 and ß = -0.140) and PCS (ß = -0.150 and ß = -0.082) using SEM analysis, whereas ERI was considerably higher than in JSI. In addition, OC and JS mediated the association between The ERI and JSI with HRQoL. CONCLUSIONS: We found the ERI index is significantly correlated with HRQoL superior to JSI, in particular among Taiwan civil servants. Further longitudinal studies are needed to determine the causality and spatiotemporal relation of these differences. Int J Occup Med Environ Health. 2022;35(4):425-36.

Strengthening Capacity for Implementation Research Amid COVID-19 Pandemic: Learnings From the Global Alliance for Chronic Diseases Implementation Science School

Objective: To describe the design, delivery and evaluation of the 3rd Global Alliance for Chronic Diseases (GACD) Implementation Science School (ISS), delivered virtually in 2020 for the first time. Methods: Since 2014, GACD has supported the delivery of more than ten Implementation Science Workshops for more than 500 international participants. It has also been conducting an annual ISS since 2018. In this study, we described the design, delivery and evaluation of the third ISS. Results: Forty-six participants from 23 countries in five WHO regions attended the program. The virtual delivery was well-received and found to be efficient in program delivery, networking and for providing collaborative opportunities for trainees from many different countries. The recently developed GACD Implementation Science e-Hub was found to be an instrumental platform to support the program by providing a stand-alone, comprehensive online learning space for knowledge and skill development in implementation research. Conclusion: The delivery of the virtual GACD ISS proved to be feasible, acceptable and effective and offers greater scalability and sustainability as part of a future strategy for capacity strengthening in implementation research globally.

Improving Patient Safety Culture During the COVID-19 Pandemic in Taiwan

Background and Aim Patient safety culture attitude is strongly linked to patient safety outcomes. Since the onset of the COVID-19 pandemic in early 2020, pandemic prevention has become the priority of hospital staff. However, few studies have explored the changes in patient safety culture among hospital staff that have occurred during the pandemic. The present study compared the safety attitudes, emotional exhaustion (EE), and work–life balance (WLB) of hospital staff in the early (2020) and late (2021) stages of the COVID-19 pandemic and explored the effects of EE and WLB on patient safety attitudes in Taiwan. Materials and Methods In this cross-sectional study, the Joint Commission of Taiwan Patient Safety Culture Survey, including the six-dimension Safety Attitudes Questionnaire (SAQ) and EE and WLB scales, were used for data collection. Results This study included a total of 706 hospital employees from a district hospital in Taipei City. The respondents' scores in each SAQ sub-dimension (except for stress recognition) increased non-significantly from 2020 to 2021, whereas their EE and WLB scores improved significantly (P < 0.05 and P < 0.01, respectively). The results of hierarchical regression analysis indicated that although a respondent's WLB score could predict their scores in each SAQ sub-dimension (except for stress recognition), EE was the most important factor affecting the respondents' attitudes toward patient safety culture during the later stage of the COVID-19 pandemic. Conclusion In the post-pandemic, employees' attitudes toward safety climate, job satisfaction, and perception of Management changed from negative to positive. Additionally, both EE and WLB are key factors influencing patient safety culture. The present study can be used as a reference for hospital managers to formulate crisis response strategies.

Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2

Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.

Decision Analysis of Multifactor Credit Risk Based on Logistic Regression and BP Neural Network

Small, medium, and micro enterprises play an important role in the development of the national economy and are of great significance in promoting technological innovation, relieving employment pressure, facilitating people’s lives, and maintaining social stability. But in China, small, medium, and micro enterprises generally exist in the phenomenon of “financing difficulties.” Therefore, we need to find a method to forecast its credit risk. By using Python, SPSS, and other software, based on a two-component logistic regression model, assisted by multievaluation model and supported by game theory, this paper establishes an innovative comprehensive credit risk assessment model for small, medium, and micro enterprises.

Religious Exemptions of Vaccine Mandates: A Short Analysis of Legal and Political Chalenges of American Society amidst the COV1D-19 Pandemic

Increasing vaccine coverage has been considered a critical measure to counter the COVID-19 pandemic. While the federal government launched a vaccination program shortly after its emergency use authorization of vaccines, the vaccine coverage of the United States is 63% that only ranks 62th around the world by mid-January, 2022. This relatively low coverage is commonly attributed to the anti-vaccine movements, and anti-intellectualism in the U.S. history, and religious exemption of vaccine mandates recognized by most state and federal laws. From a perspective of public health law and social research, this article analyzes how religious exemption challenges U.S. legal system and society (especially amidst this pandemic), as well as to explores a more sophisticated balance between public health needs and human rights protections.

Adjuvant-Protein Conjugate Vaccine with Built-In TLR7 Agonist on S1 Induces Potent Immunity against SARS-CoV-2 and Variants of Concern.

With the global pandemic of the new coronavirus disease (COVID-19), a safe, effective, and affordable mass-produced vaccine remains the current focus of research. Herein, we designed an adjuvant-protein conjugate vaccine candidate, in which the TLR7 agonist (TLR7a) was conjugated to S1 subunit of SARS-CoV-2 spike protein, and systematically compared the effect of different numbers of built-in TLR7a on the immune activity for the first time. As the number of built-in TLR7a increased, a bell-shaped reaction was observed in three TLR7a-S1 conjugates, with TLR7a(10)-S1 (with around 10 built-in adjuvant molecules on one S1 protein) eliciting a more potent immune response than TLR7a(2)-S1 and TLR7a(18)-S1. This adjuvant-protein conjugate strategy allows the built-in adjuvant to provide cluster effects and prevents systemic toxicity and facilitates the co-delivery of adjuvant and antigen. Vaccination of mice with TLR7a(10)-S1 triggered a potent humoral and cellular immunity and a balanced Th1/Th2 immune response. Meanwhile, the vaccine induces effective neutralizing antibodies against SARS-CoV-2 and all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). It is expected that the adjuvant-protein conjugate strategy has great potential to construct a potent recombinant protein vaccine candidate against various types of diseases.