Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.

Additional mutations based on Omicron BA.2.75 mediate its further evasion from broadly neutralizing antibodies

SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with that against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants. Graphical

Additional mutations based on Omicron BA.2.75 mediate its further evasion from broadly neutralizing antibodies.

SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with those against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants.

The Impact of Hygiene Factors on Online Hotel Consumption in China during the COVID-19 Pandemic

The COVID-19 pandemic, with its risk of repeated fluctuations, has shifted the basis for decisions on tourism spending. Thus, it is crucial for the hospitality industry to understand the factors that influence accommodation consumption. Grounded in signaling theory, our empirical analysis is based on analyzing data from eLong on 7209 Chinese hotels using binary logistic regression and the ordinary least squares method (OLS). The main findings are as follows: (1) completeness of information, online hygiene rating and hygiene recommendation tags have a significant impact on hotel consumption;(2) online hygiene rating has a positively significant moderating effect on the relationship between information completeness and hotel sales;and (3) there is variability in the factors that influence the generation and growth of hotel sales. In addition, we discuss the role of online travel agencies (OTAs) and provide relevant advice for practitioners.

The applicability and efficacy of Micro-Video Psychological Training Camp in groups with mild to moderate symptoms of depression and anxiety: A prospective and randomized controlled trial protocol.

Background: Mental health is a global issue requiring global attention. Depression and anxiety are two of the most common mental disorders (CMDs) and are characterized by high incidence and high comorbidity. In recent years, the prolonged COVID-19 pandemic and exacerbated social instability have posed significant challenges to the mental resilience and mental health outcomes of the global population. Now more than ever, with an increase in mental health needs, it has become even more crucial to find an effective solution to provide universal mental healthcare. Psychotherapy is of vital importance for those coping with symptoms of depression and anxiety and is used to enhance mental resilience. However, such therapy can be difficult to access in reality. In this context, the Micro-Video Psychological Training Camp (MVPTC) platform will be developed. Objectives: As an online self-help platform for psychological intervention, the MVPTC platform was developed for those who suffer from mild to moderate symptoms of depression and/or anxiety and is tasked with the goal of reducing depressive and anxious symptoms while improving mental resilience. Thus, this study will be carried out to verify its efficacy and applicability. Methods: In this parallel-group, randomized controlled trial, a total of 200 mild to moderately depressed and/or anxious adults seeking self-help will be randomly recruited and assigned to either the micro-video psychological intervention group or the wait list control group. Online measurements by self-assessment will be taken at baseline, post-intervention, 1-month, and 3-month follow-up. Results: The primary results will involve symptoms of depression and anxiety. The secondary results will involve mental resilience. An analysis will be conducted based on the intention-to-treat principle. Discussion: This trial will examine whether the MVPTC platform for the relief of symptoms and the enhancement of resilience in a population screened for depression and anxiety symptoms proves effective and applicable. Large-scale resilience enhancement may benefit public mental health in terms of preventive interventions, managing depressive and anxiety symptoms, and promoting mental health. With the MVPTC-based method being applied, a brief, efficient, and structured intervention model can potentially be established, having the potential to provide necessary and accessible mental support for an extensive target group. Clinical trial registration: http://www.chictr.org.cn/, identifier ChiCTR2100043725.

Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination.

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections.

With declining SARS-CoV-2-specific antibody titers and increasing numbers of spike mutations, the ongoing emergence of Omicron subvariants causes serious challenges to current vaccination strategies. BA.2 breakthrough infections have occurred in people who have received the wild-type vaccines, including mRNA, inactivated, or recombinant protein vaccines. Here, we evaluate the antibody evasion of recently emerged subvariants BA.4/5 and BA.2.75 in two inactivated vaccine-immunized cohorts with BA.2 breakthrough infections. Compared with the neutralizing antibody titers against BA.2, marked reductions are observed against BA.2.75 in both 2-dose and 3-dose vaccine groups. In addition, although BA.2 breakthrough infections induce a certain cross-neutralization capacity against later Omicron subvariants, the original antigenic sin phenomenon largely limits the improvement of variant-specific antibody response. These findings suggest that BA.2 breakthrough infections seem unable to provide sufficient antibody protection against later subvariants such as BA.2.75 in the current immunization background with wild-type vaccines.

Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine as a heterologous booster

To overcome the increased risk of SARS-CoV-2 reinfection or post-vaccination infection caused by the Omicron variant, Omicron-specific vaccines were considered a potential strategy. We reported the increased magnitude and breadth of antibody response against VOCs elicited by post-vaccination Delta and Omicron infection, compared to WT infection without vaccination. Then, in mouse models, three doses of Omicron-RBD immunization elicited comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, a heterologous Omicron-RBD booster following two doses of WT-RBD immunization increased the NAb titers against Omicron by 9 folds than the homologous WT-RBD booster. Moreover, it retains neutralization against both WT and current VOCs. Results suggest that Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs and that SARS-CoV-2 vaccines including two or more virus lineages might improve the NAb response. Graphical

A key F27I substitution within HCDR1 facilitates the rapid maturation of P2C-1F11-like neutralizing antibodies in a SARS-CoV-2-infected donor.

Although thousands of anti-SARS-CoV-2 monoclonal neutralizing antibodies (nAbs) have been identified and well characterized, some crucial events in the development of these nAbs during viral infection remain unclear. Using deep sequencing, we explore the dynamics of antibody repertoire in a SARS-CoV-2-infected donor, from whom the potent and broad nAb P2C-1F11 (the parent version of Brii-196) was previously isolated. Further analysis shows a rapid clonal expansion of some SARS-CoV-2-specific antibodies in early infection. Longitudinal tracing of P2C-1F11 lineage antibodies reveals that these elite nAbs were rare. Using sequence alignment, structure modeling, and bioactivity analysis based on site-mutated assay, we demonstrate that a key substitution F27I in heavy chain contributes significantly to the maturation of P2C-1F11-like antibodies. Overall, our findings elucidate the developmental process and maturation pathway of P2C-1F11, providing some important information for the design of novel immunogens to elicit more potent nAbs against SARS-CoV-2 infection.

Increased resistance of SARS-CoV-2 Lambda variant to antibody neutralization.

A recently identified SARS-CoV-2 variant, Lambda, has spread to many countries around the world. Here, we measured and evaluated the reduced sensitivity of Lambda variant to the neutralization by plasma polyclonal antibodies elicited by the natural SARS-CoV-2 infection and inactivated vaccine. The combination of two substitutions appearing in the RBD of spike protein (L452Q and F490S) resulted in noticeably reduced neutralization against Lambda variant. F490S contributed more than L452Q in affecting the neutralization. In addition, the neutralization test with 12 published nAbs binding to RBD of SARS-CoV-2 with defined structures suggested that Lambda variant resisted the neutralization by some antibodies from Class 2 and Class 3. Overall, these results suggest that pre-existing antibody neutralization established by natural infection from non-Lambda variants or immunization could be significantly decreased, re-emphasizing the importance of ongoing viral mutation monitoring.

Structural and functional analysis of an inter-Spike bivalent neutralizing antibody against SARS-CoV-2 variants.

The different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted most public concern because they caused "wave and wave" COVID-19 pandemic. The initial step of viral infection is mediated by the SARS-CoV-2 Spike (S) protein, which mediates the receptor recognition and membrane fusion between virus and host cells. Neutralizing antibodies (nAbs) targeting the S protein of SARS-CoV-2 have become promising candidates for clinical intervention strategy, while multiple studies have shown that different variants have enhanced infectivity and antibody resistance. Here, we explore the structure and function of STS165, a broadly inter-Spike bivalent nAb against SARS-CoV-2 variants and even SARS-CoV, contributing to further understanding of the working mechanism of nAbs.

How and When Telework Improves Job Performance During COVID-19? Job Crafting as Mediator and Performance Goal Orientation as Moderator.

PURPOSE: Literature shows that it is a paradox whether employees can achieve performance in telework, especially during COVID-19. Our aim is to clarify the relationship between telework and employees' job performance through a moderated mediation model. METHODS: This study employed two-wave surveys with the aim of reducing the potential risk of common method bias. The 1309 participants of the survey were mainly employees who used telework during COVID-19, and they were mostly in positions such as product design and scheme planning. SEM was used to test the hypotheses. RESULTS: Results from two-wave surveys of 1309 Chinese employees indicated that telework positively influenced job performance via job crafting. That is, job crafting played a mediating role between telework and job performance. And performance-prove goal orientation positively moderated the relationship between telework and job crafting but performance-avoid goal orientation negatively moderated the relationship between them. CONCLUSION: This study shows that telework can improve job performance through job crafting in COVID-19, in response to the paradox implied in the literature. In addition, we use COR theory to explain the role of performance goal orientation and job crafting in telework. We add these variables to the theoretical framework of COR theory, thereby enriching the theoretical research from the COR theory perspective.

A fourth dose of Omicron RBD vaccine enhances broad neutralization against SARS-CoV-2 variants including BA.1 and BA.2 in vaccinated mice.

The SARS-CoV-2 vaccines have been widely used to build an immunologic barrier in the population against the COVID-19 pandemic. However, a newly emerging Omicron variant, including BA.1, BA.1.1, BA.2, and BA.3 sublineages, largely escaped the neutralization of existing neutralizing antibodies (nAbs), even those elicited by three doses of vaccines. Here, we used the Omicron BA.1 RBD as a fourth dose of vaccine to induce potent Omicron-specific nAbs and evaluated the broadly neutralizing activities against SARS-CoV-2 variants. The BA.1-based vaccine was indeed prone to induce a strain-specific antibody response substantially cross-reactive with BA.2 sublineage, and yet triggered broad neutralization against SARS-CoV-2 variants when it was used in the sequential immunization with WT and other variant vaccines. These results demonstrated that the booster of Omicron RBD vaccine could be a rational strategy to enhance the broadly nAb response.

Sequential immunization with SARS-CoV-2 RBD vaccine induces potent and broad neutralization against variants in mice.

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.

Survey of low pathogenic avian influenza viruses in live poultry markets in Guangxi Province, Southern China, 2016-2019.

Low pathogenic avian influenza viruses (LPAIVs) have been widespread in poultry and wild birds throughout the world for many decades. LPAIV infections are usually asymptomatic or cause subclinical symptoms. However, the genetic reassortment of LPAIVs may generate novel viruses with increased virulence and cross-species transmission, posing potential risks to public health. To evaluate the epidemic potential and infection landscape of LPAIVs in Guangxi Province, China, we collected and analyzed throat and cloacal swab samples from chickens, ducks and geese from the live poultry markets on a regular basis from 2016 to 2019. Among the 7,567 samples, 974 (12.87%) were LPAIVs-positive, with 890 single and 84 mixed infections. Higher yearly isolation rates were observed in 2017 and 2018. Additionally, geese had the highest isolation rate, followed by ducks and chickens. Seasonally, spring had the highest isolation rate. Subtype H3, H4, H6 and H9 viruses were detected over prolonged periods, while H1 and H11 viruses were detected transiently. The predominant subtypes in chickens, ducks and geese were H9, H3, and H6, respectively. The 84 mixed infection samples contained 22 combinations. Most mixed infections involved two subtypes, with H3 + H4 as the most common combination. Our study provides important epidemiological data regarding the isolation rates, distributions of prevalent subtypes and mixed infections of LPAIVs. These results will improve our knowledge and ability to control epidemics, guide disease management strategies and provide early awareness of newly emerged AIV reassortants with pandemic potential.

Differences in terms of presentation and outcomes between patients with lung cancer as opposed to other solid organ cancer after infection with SARS-CoV-2: protocol for a systematic review.

INTRODUCTION: Scholars believe that COVID-19 can be particularly lethal for patients with cancer. Some studies found that COVID-19 appears to be more lethal in patients with lung cancer than in other cancer patients. In order to take appropriate measures to balance a delay in lung cancer treatment against the risk for a potential COVID-19 exposure, we first need to know whether patients with lung cancer have special risks. We aim to conduct a systematic review and meta-analysis to examine differences in terms of presentation and outcomes between patients with lung cancer as opposed to other solid organ cancer after infection with SARS-CoV-2. METHODS AND ANALYSIS: A comprehensive search of published original research studies will be performed in Embase, MEDLINE, Web of Science, WangFangData, CQVIP, COMPENDEX and CNKI. The medRxiv preprint server will also be searched for applicable studies (grey literature). Original research studies will be included if they include patients with: (A) laboratory-confirmed SARS-CoV-2 infection and (B) confirmed solid cancer, and (C) measurable clinical presentation or outcome, such as mortality rate, intensive care unit admission rate, incidence of pneumonia. One author will conduct the electronic database searches, two authors will independently screen studies, two will extract data and two will assess study quality. If I² exceeds 60% for the pooled analysis, we will explore sources of heterogeneity in subgroups of studies. We will use fixed-effect, random-effects or mixed-effects models to estimate the relative risk or OR. If the data reporting allows, a subgroup analysis between non-small cell lung cancer and small cell lung cancer patients will be performed. ETHICS AND DISSEMINATION: The proposed study will not collect individual-level data and, therefore, does not require ethical approval. We will submit our findings to a peer-reviewed scientific journal and will disseminate results through presentations at international scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42020190118.