Modeling the competitive transmission of the Omicron strain and Delta strain of COVID-19.

Since November 2021, there have been cases of COVID-19's Omicron strain spreading in competition with Delta strains in many parts of the world. To explore how these two strains developed in this competitive spread, a new compartmentalized model was established. First, we analyzed the fundamental properties of the model, obtained the expression of the basic reproduction number, proved the local and global asymptotic stability of the disease-free equilibrium. Then by means of the cubic spline interpolation method, we obtained the data of new Omicron and Delta cases in the United States of new cases starting from December 8, 2021, to February 12, 2022. Using the weighted nonlinear least squares estimation method, we fitted six time series (cumulative confirmed cases, cumulative deaths, new cases, new deaths, new Omicron cases, and new Delta cases), got estimates of the unknown parameters, and obtained an approximation of the basic reproduction number in the United States during this time period as R 0 ≈ 1.5165 . Finally, each control strategy was evaluated by cost-effectiveness analysis to obtain the optimal control strategy under different perspectives. The results not only show the competitive transmission characteristics of the new strain and existing strain, but also provide scientific suggestions for effectively controlling the spread of these strains.

Modeling the competitive transmission of the Omicron strain and Delta strain of COVID-19

Since November 2021, there have been cases of COVID-19's Omicron strain spreading in competition with Delta strains in many parts of the world. To explore how these two strains developed in this competitive spread, a new compartmentalized model was established. First, we analyzed the fundamental properties of the model, obtained the expression of the basic reproduction number, proved the local and global asymptotic stability of the disease-free equilibrium. Then by means of the cubic spline interpolation method, we obtained the data of new Omicron and Delta cases in the United States of new cases starting from December 8, 2021, to February 12, 2022. Using the weighted nonlinear least squares estimation method, we fitted six time series (cumulative confirmed cases, cumulative deaths, new cases, new deaths, new Omicron cases, and new Delta cases), got estimates of the unknown parameters, and obtained an approximation of the basic reproduction number in the United States during this time period as

Financial impact of cost of capital on tourism-based SMEs in COVID-19: implications for tourism disruption mitigation.

Opportunities for funding Tourism SMEs are emerging globally due to the expansion of tourism sector. However, it is still being determined how these financial arrangements will be controlled at more significant sizes equitably. In the contemporary period, E7 economy is deficient in producing the financial resources to ensure the availability of funds for the acquisition of funds for tourism-based SMEs. However, this research tested the empirical position of cost of debt in E-7 economies during COVID-19 crises. Study findings have shown significant outcomes between the constructs. The variation of conditions, structural uncertainty, transection systems, and variation in support by the financial institution for tourism-based SMEs are the main reasons that lessen borrowing and lending system of funds, from banks to SMEs. However, theorists must revisit the transaction system of debt financing for SMEs. Policymakers are suggested to develop viable and SME system-friendly policies to finance through debt capital from the banks in the time of structural imposed crises, like COVID-19.

Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium.

The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike. Most IgGs that do not neutralize Omicron bind either entirely monovalently or have some (22%-50%) monovalent occupancy. Cleavage of bivalent-binding IgGs to Fabs abolishes neutralization and binding affinity, with disproportionate loss of activity against Omicron pseudovirus and spike. These results suggest that VoC-resistant antibodies overcome mutagenic substitution via avidity. Hence, vaccine strategies targeting future SARS-CoV-2 variants should consider epitope display with spacing and organization identical to trimeric spike.

How to reduce the exposure risk of medical staff from SARS-CoV-2 by reducing environmental contamination: Experience from designated hospitals in China.

Background: Using daily monitoring of environmental surfaces and personal protective equipment (PPE), we found an increase in environmental contamination since August 18, 2021, in a designated hospital for COVID-19 patients in China, which may lead to an increased risk of exposure to medical staff. Methods: To investigate the cause of increased environmental contamination and effect of our intervention, we obtained environmental samples at pre-intervention (August 18-21, 2021) and post-intervention (August 22-28, 2021) from six infection isolation rooms with windows for ventilation and other auxiliary areas at 105 and 129 sites before routine daily cleaning, respectively. In addition, we obtained PPE samples from 98 medical staff exiting the patient rooms/contaminated areas at 482 sites. Between August 22 and 24, 2021, we took measures to reduce environmental contamination based on sampling and inspection results. Findings: At pre-intervention, the positivity rates for contamination of environmental surfaces and PPE samples were significantly higher for critical patients (37.21 and 27.86%, respectively) than severely ill patients (25.00 and 12.50%, respectively) and moderately ill patients (0.00 and 0.00%, respectively) (Pearson's Chi-square: χ2 = 15.560, p = 0.000; Fisher's exact test: χ2 = 9.358, p = 0.007). Therefore, we inferred that the source of contamination of environmental surfaces and PPE was mainly the room of critically ill patients, likely through the hands of medical staff to the potentially contaminated areas. A critically ill patient had emergency tracheal intubation and rescue on August 18, 2021, due to worsened patient condition. The ventilator tube used for first aid did not match the ventilator, and the ventilator tube fell off multiple times on August 18-21, 2021, which may explain the increased contamination of environmental surfaces and PPE from critically ill patients, as well as lead to indirect contamination of potentially contaminated areas. The contamination positivity rates of environmental surfaces and PPE were reduced by replacing the appropriate ventilator catheter, limiting the number of people entering the isolation room simultaneously, increasing the frequency of environmental disinfection, standardizing the undressing process, setting up undressing monitoring posts to supervise the undressing process, and preventing the spread of virus infections in the hospital during an epidemic. Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was spread on object surfaces in isolation rooms mainly by touch, and the contamination of environmental surfaces and PPE was greater in rooms of patients with greater disease severity and higher surface touch frequency. Therefore, strict protective measures for medical staff, frequent environmental cleaning for isolation rooms, and compliance with mask wearing by patients when conditions permit should be advised to prevent SARS-CoV-2 spread in hospitals.

Longitudinal analysis of risk factors associated with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among hemodialysis patients and healthcare personnel in outpatient hemodialysis centers

In this prospective, longitudinal study, we examined the risk factors for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among a cohort of chronic hemodialysis (HD) patients and healthcare personnel (HCPs) over a 6-month period. The risk of SARS-CoV-2 infection among HD patients and HCPs was consistently associated with a household member having SARS-CoV-2 infection.

Optimal Control Strategy of an Online Game Addiction Model with Incomplete Recovery.

Since the global COVID-19 pandemic in 2020, some people who have dropped out of online game have become re-addicted to it due to the order of stay-at-home, making the phenomenon of online game addiction even worse. Controlling the prevalence of online game addiction is of great significance to protect people's healthy life. For this purpose, a mathematical model of online game addiction with incomplete recovery and relapse is established. First, we analyze the basic properties of the model and obtain the expression of the basic reproduction number and all equilibria. By constructing suitable Lyapunov functions, the global asymptotical stability of the equilibria are proved. Then in the numerical simulation, we use the least squares estimation method to fit the real data of e-sports users in China from 2010 to 2020, and obtain the estimated value of all parameters. The approximation value of the basic reproduction number is obtained as R 0 ≈ 5.05 . The result reflects that the spread of game addiction in China is very serious. The stability of the equilibria are proved by using the estimated parameter values. Finally, the simulation results between with control and without control during 2020 to 2050 are compared, and the optimal control strategy is found by comparing the total infectious people. The results of optimal control suggest that if we increase our continuous attention to incompletely recovered people, we can prevent more people from becoming addicted to games. The findings in this paper reveal new mechanisms of game addiction transmission and demonstrate a more detailed and reliable control strategy.

Research on the treatment based on syndrome differentiation of COVID-19 according to the theory of Guangwenyilun

COVID-19is highly infectious and epidemic, which belongs to the " plague" disease of traditional Chinese medicine and seriously endangers the safety of human life. Based on the theory of Guangwenyilun combined with the treatment experience of COVID-19 in TCM, syndrome differentiation-based treatment and the clinical characteristic of COVID-19is be- ing deeply analysed. COVID-19began because of the" epidemic pathogenic factors", and the pathogenesis is that the dampness and heat generated toxin which blocked the qi movement. The early onset of this disease is in the pleurodiaphragmatic inter- space, and its transmission can be divided into sequential transmission and reverse transmission. Regardless of the direction of its transmission, grasping the transmission of" epidemic pathogenic factors" on the diagnosis and treatment combined with " five distinguishing thought, exterior and interior, accompanying symptoms" theory will be of great importance to help to im- prove the effect of treatment. At the same time, this clinical approach will also provide reference for the diagnosis and treat- ment of any possible new diseases.

An Outbreak of SARS-CoV-2 Omicron Subvariant BA.2.76 in an Outdoor Park - Chongqing Municipality, China, August 2022.

What is already known about this topic?: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant has a stronger transmission capacity and faster transmission speed than the previous strain. What is added by this report?: The first coronavirus disease 2019 (COVID-19) case infected with the SARS-CoV-2 Omicron subvariant BA.2.76 who caused local transmission was reported in Chongqing Municipality on August 16, 2022. For 35 minutes, the Patient Zero jogged along a lake at a local park without wearing a mask. Among the 2,836 people potentially exposed at the time, 39 tested positive. Overall, 38 out of 39 cases did not wear a mask on the morning of August 16. All 39 cases lacked any previous exposure to the variant before testing positive on their nucleic acid test. What are the implications for public health practice?: It is essential to maintain personal wellbeing by ensuring one maintains personal protection and follows regulated guidelines such as maintaining safe distances from others both indoors and outdoors.

Neutralizing antibodies from the rare convalescent donors elicited antibody-dependent enhancement of SARS-CoV-2 variants infection.

Currently, neutralizing antibody and vaccine strategies have been developed by targeting the SARS-CoV-2 strain identified during the early phase of the pandemic. Early studies showed that the ability of SARS-CoV-2 RBD or NTD antibodies to elicit infection enhancement in vivo is still controversial. There are growing concerns that the plasma and neutralizing antibodies from convalescent patients or people receiving vaccines mediate ADE of SARS-CoV-2 variants infections in immune cells. Here, we constructed engineered double-mutant variants containing an RBD mutation and D614G in the spike (S) protein and natural epidemic variants to gain insights into the correlation between the mutations in S proteins and the ADE activities and tested whether convalescent plasma and TOP10 neutralizing antibodies in our laboratory mediated the ADE effects of these SARS-CoV-2 variants. We found that one out of 29 convalescent plasma samples caused the ADE effect of pandemic variant B.1.1.7 and that the ADE effect of wild-type SARS-CoV-2 was not detected for any of these plasma samples. Only one antibody, 55A8, from the same batch of convalescent patients mediated the ADE effects of multiple SARS-CoV-2 variants in vitro, including six double-mutant variants and four epidemic variants, suggesting that ADE activities may be closely related to the antibody itself and the SARS-CoV-2 variants' S proteins. Moreover, the ADE activity of 55A8 depended on FcγRII on immune cells, and the introduction of LALA mutations at the Fc end of 55A8 eliminated the ADE effects in vitro, indicating that 55A8LALA may be a clinical drug used to prevent SARS-CoV-2 variants. Altogether, ADE may occur in rare convalescent patients or vaccinees with ADE-active antibodies who are then exposed to a SARS-CoV-2 variant. These data suggested that potential neutralizing antibodies may need to undergo ADE screening tests for SARS-CoV-2 variants, which should aid in the future design of effective antibody-based therapies.

Genetic engineering of baculovirus-insect cell system to improve protein production.

The Baculovirus Expression Vector System (BEVS), a mature foreign protein expression platform, has been available for decades, and has been effectively used in vaccine production, gene therapy, and a host of other applications. To date, eleven BEVS-derived products have been approved for use, including four human vaccines [Cervarix against cervical cancer caused by human papillomavirus (HPV), Flublok and Flublok Quadrivalent against seasonal influenza, Nuvaxovid/Covovax against COVID-19], two human therapeutics [Provenge against prostate cancer and Glybera against hereditary lipoprotein lipase deficiency (LPLD)] and five veterinary vaccines (Porcilis Pesti, BAYOVAC CSF E2, Circumvent PCV, Ingelvac CircoFLEX and Porcilis PCV). The BEVS has many advantages, including high safety, ease of operation and adaptable for serum-free culture. It also produces properly folded proteins with correct post-translational modifications, and can accommodate multi-gene- or large gene insertions. However, there remain some challenges with this system, including unstable expression and reduced levels of protein glycosylation. As the demand for biotechnology increases, there has been a concomitant effort into optimizing yield, stability and protein glycosylation through genetic engineering and the manipulation of baculovirus vector and host cells. In this review, we summarize the strategies and technological advances of BEVS in recent years and explore how this will be used to inform the further development and application of this system.

Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice.

The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.

Optimal Control Strategy of an Online Game Addiction Model with Incomplete Recovery

Since the global COVID-19 pandemic in 2020, some people who have dropped out of online game have become re-addicted to it due to the order of stay-at-home, making the phenomenon of online game addiction even worse. Controlling the prevalence of online game addiction is of great significance to protect people’s healthy life. For this purpose, a mathematical model of online game addiction with incomplete recovery and relapse is established. First, we analyze the basic properties of the model and obtain the expression of the basic reproduction number and all equilibria. By constructing suitable Lyapunov functions, the global asymptotical stability of the equilibria are proved. Then in the numerical simulation, we use the least squares estimation method to fit the real data of e-sports users in China from 2010 to 2020, and obtain the estimated value of all parameters. The approximation value of the basic reproduction number is obtained as

Genetic engineering of baculovirus-insect cell system to improve protein production

The Baculovirus Expression Vector System (BEVS), a mature foreign protein expression platform, has been available for decades, and has been effectively used in vaccine production, gene therapy, and a host of other applications. To date, eleven BEVS-derived products have been approved for use, including four human vaccines [Cervarix against cervical cancer caused by human papillomavirus (HPV), Flublok and Flublok Quadrivalent against seasonal influenza, Nuvaxovid/Covovax against COVID-19], two human therapeutics [Provenge against prostate cancer and Glybera against hereditary lipoprotein lipase deficiency (LPLD)] and five veterinary vaccines (Porcilis Pesti, BAYOVAC CSF E2, Circumvent PCV, Ingelvac CircoFLEX and Porcilis PCV). The BEVS has many advantages, including high safety, ease of operation and adaptable for serum-free culture. It also produces properly folded proteins with correct post-translational modifications, and can accommodate multi-gene– or large gene insertions. However, there remain some challenges with this system, including unstable expression and reduced levels of protein glycosylation. As the demand for biotechnology increases, there has been a concomitant effort into optimizing yield, stability and protein glycosylation through genetic engineering and the manipulation of baculovirus vector and host cells. In this review, we summarize the strategies and technological advances of BEVS in recent years and explore how this will be used to inform the further development and application of this system.

Characterization and immunogenicity of SARS-CoV-2 spike proteins with varied glycosylation.

The ongoing coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drastically changed our way of life and continues to have an unmitigated socioeconomic impact across the globe. Research into potential vaccine design and production is focused on the spike (S) protein of the virus, which is critical for virus entry into host cells. Yet, whether the degree of glycosylation in the S protein is associated with vaccine efficacy remains unclear. Here, we first optimized the expression of the S protein in mammalian cells. While we found no significant discrepancy in purity, homogeneity, or receptor binding ability among S proteins derived from 293F cells (referred to as 293F S-2P), 293S GnTI- cells (defective in N-acetylglucosaminyl transferase I enzyme; 293S S-2P), or TN-5B1-4 insect cells (Bac S-2P), there was significant variation in the glycosylation patterns and thermal stability of the proteins. Compared with the partially glycosylated 293S S-2P or Bac S-2P, the fully glycosylated 293F S-2P exhibited higher binding reactivity to convalescent sera. In addition, 293F S-2P induced higher IgG and neutralizing antibody titres than 293S or Bac S-2P in mice. Furthermore, a prime-boost-boost regimen, using a combined immunization of S-2P proteins with various degrees of glycosylation, elicited a more robust neutralizing antibody response than a single S-2P alone. Collectively, this study provides insight into ways to design a more effective SARS-CoV-2 immunogen.

A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rapidly spreading worldwide. Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections. However, the emergence of SARS-CoV-2 variants of concern (VOCs), such as Delta (B.1.617.2) and the recently emerged Omicron (B.1.1.529), has seriously challenged the application of current therapeutics. Therefore, there is still a pressing need for identification of new broad-spectrum antivirals. Here, we further characterized a human antibody (58G6), which we previously isolated from a patient, with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations (IC50) of 1.69 ng/ml and 54.31 ng/ml, respectively. 58G6 shows prophylactic and therapeutic efficacy in hamsters challenged with the Delta and Omicron variants through nasal delivery. Notably, a very low dosage (2 mg/kg daily) of 58G6 efficiently prevented Omicron variant replication in the lungs. These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection. In general, 58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants. To the best of our knowledge, 58G6 is one of the most potent neutralizing antibodies against Omicron, with a broader spectrum than those approved for clinical use. 58G6 could be developed as a nebulized therapy, which would be more cost effective and user friendly and enhance the clinical outcome compared to that obtained with direct nasal delivery.

Optimal control and cost-effectiveness analysis of a new COVID-19 model for Omicron strain.

Omicron, a mutant strain of COVID-19, has been sweeping the world since November 2021. A major characteristic of Omicron transmission is that it is less harmful to healthy adults, but more dangerous for people with underlying disease, the elderly, or children. To simulate the spread of Omicron in the population, we developed a new 9-dimensional mathematical model with high-risk and low-risk exposures. Then we analyzed its dynamic properties and obtain the basic reproduction number R 0 . With the data of confirmed cases from March 1, 2022 published on the official website of Shanghai, China, we used the weighted nonlinear least square estimation method to estimate the parameters, and get the basic reproduction number R 0 ≈ 1 . 5118 . Finally, we considered three control measures (isolation, detection and treatment), and studied the optimal control strategy and cost-effectiveness analysis of the model. The control strategy G is determined to be the optimal control strategy from the purpose of making fewer people infected. In strategy G, the three human control measures contain six control variables, and the control strength of these variables needs to be varied according to the pattern shown in Figure 11, so that the number of infections can be minimized and the percentage of reduction of infections can reach more than 95%.

Epidemiological investigation of an imported COVID-19 case infected with Delta variant from Nepal in Chongqing of China

Objective: To analyze the epidemiological characteristics of a COVID-19 case imported from Nepal in Chongqing of China, and provide evidence for the prevention and control of imported COVID-19.

The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.