Factors that impacted mobile-payment adoption in China during the COVID-19 pandemic.

The Unified Theory of Acceptance and Use of Technology (UTAUT) is a potential paradigm for explaining technology adoption and can be applied to a wide range of scenarios. During the COVID-19 (C-19) outbreak in China, mobile-payment platforms (Mpayment) were used extensively in everyday life because they allowed people to avoid direct and indirect connections during transactions, adhere to social-distancing guidelines, and support social-economic stabilization. By exploring the technological and psychological variables that influenced user Mpayment-adoption intentions during the C-19 pandemic, this study broadens the literature on technology adoption in emergency circumstances and expands the UTAUT. A total of 593 complete samples were collected online, with SPSS used for data analysis. The empirical findings reveal that performance expectancy, trust, perceived security, and social influence all had a significant influence on Mpayment acceptance during the C-19 outbreak, with social distancing having the greatest impact, followed by fear of C-19. Interestingly, perceived-effort expectancy had a negative influence on payment acceptance. These findings suggest that future studies should apply the expanded model to different countries and areas to investigate the impact of the C-19 pandemic on Mpayment acceptance.

Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants.

Mucosal immunity plays a significant role in the first-line defense against viruses transmitted and infected through the respiratory system, such as SARS-CoV-2. However, the lack of effective and safe adjuvants currently limits the development of COVID-19 mucosal vaccines. In the current study, we prepare an intranasal vaccine containing cationic crosslinked carbon dots (CCD) and a SARS-CoV-2 antigen, RBD-HR with spontaneous antigen particlization. Intranasal immunization with CCD/RBD-HR induces high levels of antibodies with broad-spectrum neutralization against authentic viruses/pseudoviruses of Omicron-included variants and protects immunized female BALB/c mice from Omicron infection. Despite strong systemic cellular immune response stimulation, the intranasal CCD/RBD-HR vaccine also induces potent mucosal immunity as determined by the generation of tissue-resident T cells in the lungs and airway. Moreover, CCD/RBD-HR not only activates professional antigen-presenting cells (APCs), dendritic cells, but also effectively targets nasal epithelial cells, promotes antigen binding via sialic acid, and surprisingly provokes the antigen-presenting of nasal epithelial cells. We demonstrate that CCD is a promising intranasal vaccine adjuvant for provoking strong mucosal immunity and might be a candidate adjuvant for intranasal vaccine development for many types of infectious diseases, including COVID-19.

A recombinant spike‐XBB.1.5 protein vaccine induces broad‐spectrum immune responses against XBB.1.5‐included Omicron variants of SARS‐CoV‐2

The XBB.1.5 subvariant has drawn great attention owing to its exceptionality in immune evasion and transmissibility. Therefore, it is essential to develop a universally protective coronavirus disease 2019 vaccine against various strains of Omicron, especially XBB.1.5. In this study, we evaluated and compared the immune responses induced by six different spike protein vaccines targeting the ancestral or various Omicron strains of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in mice. We found that spike‐wild‐type immunization induced high titers of neutralizing antibodies (NAbs) against ancestral SARS‐CoV‐2. However, its activity in neutralizing Omicron subvariants decreased sharply as the number of mutations in receptor‐binding domain (RBD) of these viruses increased. Spike‐BA.5, spike‐BF.7, and spike‐BQ.1.1 vaccines induced strong NAbs against BA.5, BF.7, BQ.1, and BQ.1.1 viruses but were poor in protecting against XBB and XBB.1.5, which have more RBD mutations. In sharp contrast, spike‐XBB.1.5 vaccination can activate strong and broadly protective immune responses against XBB.1.5 and other common subvariants of Omicron. By performing correlation analysis, we found that the NAbs titers were negatively correlated with the number of RBD mutations in the Omicron subvariants. Vaccines with more RBD mutations can effectively overcome the immune resistance caused by the accumulation of RBD mutations, making spike‐XBB.1.5 the most promising vaccine candidate against universal Omicron variants.

Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5‐included SARS‐CoV‐2 variants than homologous vaccination of mRNA vaccine

BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild‐type SARS‐CoV‐2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full‐length spike protein sequence‐based mRNA vaccine as the "priming” shot and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine referred to as RBD–HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD–HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5‐included SARS‐CoV‐2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long‐lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD–HR/trimer following two‐dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD–HR/trimer vaccine becomes an appropriate candidate for a booster immune injection. We prepared a Delta full‐length spike protein sequence‐based mRNA vaccine (Figure A, B) and developed a recombinant trimeric receptor‐binding domain (RBD) protein vaccine (Figure C). Later, the mRNA vaccine was injected as the "priming” shot, and the RBD–HR/trimer vaccine was used as a third heterologous booster (Figure D).

Trimeric protein vaccine based on Beta variant elicits robust immune response against BA.4/5-included SARS-CoV-2 Omicron variants.

The current Coronavirus Disease 2019 (COVID-19) pandemic, induced by newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, posed great threats to global public health security. There is an urgent need to design effective next­generation vaccines against Omicron lineages. Here, we investigated the immunogenic capacity of the vaccine candidate based on the receptor binding domain (RBD). An RBDß-HR self-assembled trimer vaccine including RBD of Beta variant (containing K417, E484 and N501) and heptad repeat (HR) subunits was developed using an insect cell expression platform. Sera obtained from immunized mice effectively blocked RBD-human angiotensin-converting enzyme 2 (hACE2) binding for different viral variants, showing robust inhibitory activity. In addition, RBDß-HR/trimer vaccine durably exhibited high titers of specific binding antibodies and high levels of cross-protective neutralizing antibodies against newly emerging Omicron lineages, as well as other major variants including Alpha, Beta, and Delta. Consistently, the vaccine also promoted a broad and potent cellular immune response involving the participation of T follicular helper (Tfh) cells, germinal center (GC) B cells, activated T cells, effector memory T cells, and central memory T cells, which are critical facets of protective immunity. These results demonstrated that RBDß-HR/trimer vaccine candidates provided an attractive next-generation vaccine strategy against Omicron variants in the global effort to halt the spread of SARS-CoV-2.

Heterologous vaccination with subunit protein vaccine induces a superior neutralizing capacity against BA.4/5-included SARS-CoV-2 variants than homologous vaccination of mRNA vaccine.

BA.4 and BA.5 (BA.4/5), the subvariants of Omicron, are more transmissible than BA.1 with more robust immune evasion capability because of its unique spike protein mutations. In light of such situation, the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in desperate need of the third booster. It has been reported that heterologous boosters might produce more effective immunity against wild-type SARS-CoV-2 and the variants. Additionally, the third heterologous protein subunit booster should be considered potentially. In the present study, we prepared a Delta full-length spike protein sequence-based mRNA vaccine as the "priming" shot and developed a recombinant trimeric receptor-binding domain (RBD) protein vaccine referred to as RBD-HR/trimer as a third heterologous booster. Compared to the homologous mRNA group, the heterologous group (RBD-HR/trimer vaccine primed with two mRNA vaccines) induced higher neutralizing antibody titers against BA.4/5-included SARS-CoV-2 variants. In addition, heterologous vaccination exhibited stronger cellular immune response and long-lasting memory response than the homologous mRNA vaccine. In conclusion, a third heterologous boosting with RBD-HR/trimer following two-dose mRNA priming vaccination should be a superior strategy than a third homologous mRNA vaccine. The RBD-HR/trimer vaccine becomes an appropriate candidate for a booster immune injection.

BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.

Bruton's tyrosine kinase (BTK) is an essential component of multiple signaling pathways that regulate B cell and myeloid cell proliferation, survival, and functions, making it a promising therapeutic target for various B cell malignancies and inflammatory diseases. Five small molecule inhibitors have shown remarkable efficacy and have been approved to treat different types of hematological cancers, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, and orelabrutinib. The first-in-class agent, ibrutinib, has created a new era of chemotherapy-free treatment of B cell malignancies. Ibrutinib is so popular and became the fourth top-selling cancer drug worldwide in 2021. To reduce the off-target effects and overcome the acquired resistance of ibrutinib, significant efforts have been made in developing highly selective second- and third-generation BTK inhibitors and various combination approaches. Over the past few years, BTK inhibitors have also been repurposed for the treatment of inflammatory diseases. Promising data have been obtained from preclinical and early-phase clinical studies. In this review, we summarized current progress in applying BTK inhibitors in the treatment of hematological malignancies and inflammatory disorders, highlighting available results from clinical studies.

Oral Azvudine (FNC) Tablets in Patients infected with SARS-CoV-2 Omicron Variant: A Retrospective Cohort Study (preprint)

BackgroundThere is a lack of data on the efficacy of oral Azvudine in Coronavirus Disease treatment. This study aimed to assess the association between Azvudine treatment and clinical outcomes in a cohort of patients infected with the SARS-CoV-2 Omicron variant. MethodsThis is a retrospective study conducted in two mobile cabin hospitals. All consecutive patients with a diagnosis of COVID-19 admitted from August to October 2022 were included in the study. Linear regression models and Cox proportional hazards models were used to assess the association between Azvudine treatment and time to obtain the first negative nucleic acid test results. ResultsA total of 207 patients were analyzed, of whom 166 patients (80.2%) received Azvudine treatment after hospitalization, and the rest did not. Linear regression models showed that Azvudine treatment was associated with reduced time to obtain the first negative nucleic acid test results after adjusting for age and gender [mean difference = -1.658; 95% CI: -2.772 to -0.544, P = 0.0039]. The multivariable Cox analysis conforms to the results from the linear regression model (hazard ratio = 1.461; 95% CI: 1.01 to 2.11, P = 0.044). ConclusionAzvudine treatment was associated with reduced virus shedding time. Further studies are needed to confirm our findings.

A self-assembled trimeric protein vaccine induces protective immunity against Omicron variant.

The recently emerged Omicron (B.1.1.529) variant has rapidly surpassed Delta to become the predominant circulating SARS-CoV-2 variant, given the higher transmissibility rate and immune escape ability, resulting in breakthrough infections in vaccinated individuals. A new generation of SARS-CoV-2 vaccines targeting the Omicron variant are urgently needed. Here, we developed a subunit vaccine named RBD-HR/trimer by directly linking the sequence of RBD derived from the Delta variant (containing L452R and T478K) and HR1 and HR2 in SARS-CoV-2 S2 subunit in a tandem manner, which can self-assemble into a trimer. In multiple animal models, vaccination of RBD-HR/trimer formulated with MF59-like oil-in-water adjuvant elicited sustained humoral immune response with high levels of broad-spectrum neutralizing antibodies against Omicron variants, also inducing a strong T cell immune response in vivo. In addition, our RBD-HR/trimer vaccine showed a strong boosting effect against Omicron variants after two doses of mRNA vaccines, featuring its capacity to be used in a prime-boost regimen. In mice and non-human primates, RBD-HR/trimer vaccination could confer a complete protection against live virus challenge of Omicron and Delta variants. The results qualified RBD-HR/trimer vaccine as a promising next-generation vaccine candidate for prevention of SARS-CoV-2, which deserved further evaluation in clinical trials.

Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells.

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.

Developing cellulosic functional materials from multi-scale strategy and applications in flexible bioelectronic devices.

With the forthcoming of the post-COVID-19 and the ageing era, the novel biomaterials and bioelectronic devices are attracting more and more attention and favor. Cellulose as one of the most globe-abundant natural macromolecules has multiple merits of biocompatibility, processability, carbon neutral feature and mechanical designability. Due to its progressive advancement of multi-scale design from macro to micro followed by new cognitions, cellulose shows a promising application prospect in developing bio-functional materials. In this review, we briefly discuss the role of cellulose from the "top-down" perspective of macro-scale fibers, micro-scale nanofibers, and molecular-scale macromolecular chains for the design of advanced cellulose-based functional materials. The focus then turns to the construction and development of emerging cellulose-based flexible bioelectronic devices including biosensors, biomimetic electronic skins, and biological detection devices. Finally, the dilemma and challenge of cellulose-based bioelectronic materials and their application prospects in basic biology and medical care have been prospected.

Intranasal COVID-19 vaccines: From bench to bed.

Currently licensed COVID-19 vaccines are all designed for intramuscular (IM) immunization. However, vaccination today failed to prevent the virus infection through the upper respiratory tract, which is partially due to the absence of mucosal immunity activation. Despite the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the next generation of COVID-19 vaccine is in demand and intranasal (IN) vaccination method has been demonstrated to be potent in inducing both mucosal and systemic immune responses. Presently, although not licensed, various IN vaccines against SARS-CoV-2 are under intensive investigation, with 12 candidates reaching clinical trials at different phases. In this review, we give a detailed description about current status of IN COVID-19 vaccines, including virus-vectored vaccines, recombinant subunit vaccines and live attenuated vaccines. The ongoing clinical trials for IN vaccines are highlighted. Additionally, the underlying mechanisms of mucosal immunity and potential mucosal adjuvants and nasal delivery devices are also summarized.

The Acceptance of COVID-19 Vaccination Under Different Methods of Investigation: Based on Online and On-Site Surveys in China

As Coronavirus Disease-2019 (COVID-19) vaccines became available in December 2020, increasingly more surveys were organized to examine the acceptance of vaccination, while most of them were conducted online. This study aimed to explore the difference between online and traditional on-site surveys in terms of COVID-19 vaccine acceptance. From November to December 2020, an online survey (n = 2013) and an on-site survey (n = 4,316) were conducted simultaneously in China. Multivariate logistic regression was used to identify influencing factors of acceptance, and propensity score matching (PSM) was adopted to balance the outcomes. As a result, 90.0% of the online respondents accepted COVID-19 vaccination, while it was only 82.1% in the on-site survey. After applying PSM, the acceptance rate of the on-site survey was declined to 78.6%. The age structure, residence location, education, and health status were observed as important factors in addressing vaccination acceptance, which needed to be specifically considered when designing online surveys.

Immunological perspectives on the pathogenesis, diagnosis, prevention and treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). COVID-19 can spread to the entire body and cause multiple organ failure. It is a daunting challenge to control the fast growing worldwide pandemic because effective prevention and treatment strategies are unavailable currently. Generally, the immune response of the human body triggered by viral infection is essential for the elimination of the virus. However, severe COVID-19 patients may manifest dysregulated immune responses, such as lymphopenia, lymphocyte exhaustion, exacerbated antibody response, cytokine release syndrome (CRS), etc. Understanding of these immunological characteristics may help identify better approaches for diagnosis, prognosis and treatment of COVID-19 patients. As specific anti-viral agents are notoriously difficult to develop, strategies for modulating the immune responses by either developing novel vaccines or using immunotherapy hold great promise to improve the management of SARS-CoV-2 infection.

Vaccination Vehicles for COVID-19 Immunization - China, 2021.

BACKGROUND: Recently, developed vaccination vehicles were repurposed and deployed for coronavirus disease 2019 (COVID-19) vaccination in China. We described the vehicles and reported an evaluation of vaccination throughput of these vehicles for COVID-19 vaccination in China. METHODS: We obtained daily reports of COVID-19 vaccine doses administered in vehicles in Hubei Province between March 16 and 29 of 2021. We determined the rate of COVID-19 vaccines given and evaluated the applicability of vaccination vehicles for COVID-19 vaccination. RESULTS: Vehicles with 2 vaccination stations are suitable for several real-world scenarios. Vehicles administered an average of 72 COVID-19 vaccine doses per hour, with an upper limit of 145 doses per hour. CONCLUSION: Vaccination vehicles can save human and financial resources and provide high quality, effective, convenient, and rapid on-site vaccination services; they can increase the pace of COVID-19 vaccination.

A bivalent recombinant vaccine targeting the S1 protein induces neutralizing antibodies against both SARS-CoV-2 variants and wild-type of the virus.

The emerging variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pandemic call for the urgent development of universal corona virus disease 2019 (COVID-19) vaccines which could be effective for both wild-type SARS-CoV-2 and mutant strains. In the current study, we formulated protein subunit vaccines with AS03 adjuvant and recombinant proteins of S1 subunit of SARS-CoV-2 (S1-WT) and S1 variant (K417N, E484K, N501Y, and D614G) subunit (S1-Mut), and immunized transgenic mice that express human angiotensin-converting enzyme 2 (hACE2). The S1 protein-specific antibody production and the neutralization capability for SARS-CoV-2 and B.1.351 variant were measured after immunization in mice. The results revealed that the S1-Mut antigens were more effective in inhibiting the receptor-binding domain and ACE2 binding in B.1.351 variant than in wild-type SARS-CoV-2. Furthermore, the development of a bivalent vaccine exhibited the ideal neutralization properties against wild-type and B.1.351 variant, as well as other variants. Our findings may provide a rationale for the development of a bivalent recombinant vaccine targeting the S1 protein that can induce the neutralizing antibodies against both SARS-CoV-2 variants and wild-type of the virus and may be of importance to explore the potential clinical use of bivalent recombinant vaccine in the future.