A Beta Strain-Based Spike Glycoprotein Vaccine Candidate Induces Broad Neutralization and Protection against SARS-CoV-2 Variants of Concern.

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) are circulating worldwide, making it resistant to existing vaccines and antiviral drugs. Therefore, the evaluation of variant-based expanded spectrum vaccines to optimize the immune response and provide broad protectiveness is very important. In this study, we expressed spike trimer protein (S-TM) based on the Beta variant in a GMP-grade workshop using CHO cells. Mice were immunized twice with S-TM protein combined with aluminum hydroxide (Al) and CpG Oligonucleotides (CpG) adjuvant to evaluate its safety and efficacy. BALB/c immunized with S-TM + Al + CpG induced high neutralizing antibody titers against the Wuhan-Hu-1 strain (wild-type, WT), the Beta and Delta variants, and even the Omicron variant. In addition, compared with the S-TM + Al group, the S-TM + Al + CpG group effectively induced a stronger Th1-biased cell immune response in mice. Furthermore, after the second immunization, H11-K18 hACE2 mice were well protected from challenge with the SARS-CoV-2 Beta strain, with a 100% survival rate. The virus load and pathological lesions in the lungs were significantly reduced, and no virus was detected in mouse brain tissue. Our vaccine candidate is practical and effective for current SARS-CoV-2 VOCs, which will support its further clinical development for potential sequential immune and primary immunization. IMPORTANCE Continuous emergence of adaptive mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the use and development of existing vaccines and drugs. The value of variant-based vaccines that are capable of inducing a higher and broader protection immune response against SARS-CoV-2 variants is currently being evaluated. This article shows that a recombinant prefusion spike protein based on a Beta variant was highly immunogenic and could induced a stronger Th1-biased cell immune response in mice and was effectively protective against challenge with the SARS-CoV-2 Beta variant. Importantly, this Beta-based SARS-CoV-2 vaccine could also offer a robust humoral immune response with effectively broad neutralization ability against the wild type and different variants of concern (VOCs): the Beta, Delta, and Omicron BA.1 variants. To date, the vaccine described here has been produced in a pilot scale (200L), and the development, filling process, and toxicological safety evaluation have also been completed, which provides a timely response to the emerging SARS-CoV-2 variants and vaccine development.

Impact of the COVID-19 Pandemic on Meal Gathering in China.

During the COVID-19 pandemic, the Chinese government adopted a series of preventative measures to control the spread of the virus. This paper studies the impact of the COVID-19 pandemic and its associated prevention methods on meal sharing in China. Meal gathering during multiple periods before and after the outbreak of COVID-19 is captured through two waves of online survey across China between March and June 2020, collecting a total of 1847 observations. We employ the difference-in-difference (DID) method to identify the causal effects of COVID-19 severity on meal sharing. The results show that relative to the same period in 2019, the frequency of meal gathering decreased sharply after the initial outbreak of the coronavirus in 2020 in both epicenters and non-epicenters. Furthermore, the impact of COVID-19 differed across different types of meal sharing. Our findings have implications for consumers, food service operators, as well as policymakers to understand the social and community impact of the pandemic and to adjust their coping strategies.

Effect of the Graphene Nanosheet on Functions of the Spike Protein in Open and Closed States: Comparison between SARS-CoV-2 Wild Type and the Omicron Variant.

The spread of coronavirus disease 2019 caused by SARS-CoV-2 and its variants has become a global health crisis. Although there were many attempts to use nanomaterials-based devices to fight against SARS-CoV-2, it still remains elusive as to how the nanomaterials interact with SARS-CoV-2 and affect its biofunctions. Here, taking the graphene nanosheet (GN) as the model nanomaterial, we investigate its interaction with the spike protein in both WT and Omicron by molecular simulations. In the closed state, the GN can insert into the region between the receptor binding domain (RBD) and the N-terminal domain (NTD) in both wild type (WT) and Omicron, which keeps the RBD in the down conformation. In the open state, the GN can hamper the binding of up RBD to ACE2 in WT, but it has little impact on up RBD and, even worse, stimulates the down-to-up transition of down RBDs in Omicron. Moreover, the GN can insert in the vicinity of the fusion peptide in both WT and Omicron and prevents the detachment of S1 from the whole spike protein. The present study reveals the effect of the SARS-CoV-2 variant on the nanomaterial-spike protein interaction, which informs prospective efforts to design functional nanomaterials against SARS-CoV-2.

Has COVID-19 Changed China's Digital Trade?-Implications for Health Economics.

Digital technologies have played a significant role in the defense against the COVID-19 pandemic. This development raises the question of whether digital technologies have helped Chinese exports recover quickly and even grow. To answer this question, we study monthly data on Chinese exports to 40 countries/regions from January 2019 to June 2020 and covering 97 product categories. The study takes the COVID-19 outbreak as a natural experiment and treats digital trade products as the treatment group. Using a generalized difference-in-differences (DID) approach, we empirically investigate how this major global public health crisis and digital trade have influenced Chinese exports. Our empirical analysis reveals that the COVID-19 pandemic has inhibited China's export trade overall, digital trade has significantly promoted trade, and the supply mechanism has played a significant role in promoting the recovery of exports. Heterogeneity tests on destination countries/regions reveal that digital trade has significantly promoted exports to countries/regions with different income levels, with a more significant effect on low-risk destinations than on high-risk destinations. The sector heterogeneity test demonstrates that digital trade has enhanced the export recovery of sectors dealing in necessities for pandemic prevention. Other robustness tests, including parallel trend and placebo tests, support the above conclusions. Finally, we extend the research conclusions and discuss their implication for health economics and the practice of fighting COVID-19.

Has COVID-19 Changed China's Digital Trade?—Implications for Health Economics

Digital technologies have played a significant role in the defense against the COVID-19 pandemic. This development raises the question of whether digital technologies have helped Chinese exports recover quickly and even grow. To answer this question, we study monthly data on Chinese exports to 40 countries/regions from January 2019 to June 2020 and covering 97 product categories. The study takes the COVID-19 outbreak as a natural experiment and treats digital trade products as the treatment group. Using a generalized difference-in-differences (DID) approach, we empirically investigate how this major global public health crisis and digital trade have influenced Chinese exports. Our empirical analysis reveals that the COVID-19 pandemic has inhibited China's export trade overall, digital trade has significantly promoted trade, and the supply mechanism has played a significant role in promoting the recovery of exports. Heterogeneity tests on destination countries/regions reveal that digital trade has significantly promoted exports to countries/regions with different income levels, with a more significant effect on low-risk destinations than on high-risk destinations. The sector heterogeneity test demonstrates that digital trade has enhanced the export recovery of sectors dealing in necessities for pandemic prevention. Other robustness tests, including parallel trend and placebo tests, support the above conclusions. Finally, we extend the research conclusions and discuss their implication for health economics and the practice of fighting COVID-19.

Preclinical immunological evaluation of an intradermal heterologous vaccine against SARS-CoV-2 variants.

The recent emergence of COVID-19 variants has necessitated the development of new vaccines that stimulate the formation of high levels of neutralizing antibodies against S antigen variants. A new strategy involves the intradermal administration of heterologous vaccines composed of one or two doses of inactivated vaccine and a booster dose with the mutated S1 protein (K-S). Such vaccines improve the immune efficacy by increasing the neutralizing antibody titers and promoting specific T cell responses against five variants of the RBD protein. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that both administration schedules (i.e. "1 + 1" and "2 + 1") ensured protection against this strain. These results suggest that the aforementioned strategy is effective for protecting against new variants and enhances the anamnestic immune response in the immunized population.

COVID-19 and the Change in Lifestyle: Bodyweight, Time Allocation, and Food Choices.

We analyze the dynamic changes in individuals' lifestyle during the COVID-19 outbreak and recovery period through a survey of 1061 Chinese households. Specifically, we are interested in individuals' bodyweight, time allocation and food choices. We find that COVID-19 is associated with weight gain, less time spent on exercise and more time on entertainment. The proportion of online food purchase and snack purchases also shows an upward trend. This study provides useful implications on the impact of COVID-19 and its associated lockdowns on individuals' lifestyle and offers foresights for countries in different stages of the pandemic. It explains how encouraging exercise, managing new food purchase venues, and reducing the intake of unhealthy food such as snacks may also need to be considered in dealing with the aftermath of COVID-19.

Immune characteristics distinguish patients with severe disease associated with SARS-CoV-2.

This single-center, retrospective study aimed to explore the immune characteristics of COVID-19 and biomarkers to predict the severity of this disease. Patients infected with SARS-CoV-2 (n = 215) treated at the First Affiliated Hospital of Nanchang University from January 24 to March 12, 2020, were included in the study and classified into severe and non-severe groups. Peripheral immunocyte count and cytokine statuses were compared. The correlation between immune status, cytokine levels, and disease severity was analyzed. Leukocyte numbers were normal in both groups; however, they were relatively high (7.19 × 109/L) in patients of the severe group. Leukocyte distributions differed between the two groups; the severe group had a higher percentage of neutrophils and lower percentage of lymphocytes compared with the non-severe group, and absolute lymphocyte numbers were below normal in both groups, and particularly deficient in patients in the severe group. Lymphocyte counts have negative correlation with duration of hospital period whereas neutrophil count has no significant correlation with it. Of tested cytokines, IL-6 levels were significantly higher in the severe group (P = 0.0418). Low level of lymphocyte predicts severity of COVID-19. IL-6 levels were significantly higher in the severe group, especially in some extremely severe patients. But we did not detect the significant correlation between severity of COVID-19 with IL-6 level which may be due to limited case numbers. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of COVID-19.