Patients with Advanced Pancreatic & Biliary Cancer Appear More Vulnerable to SARS-CoV-2 Omicron Variant: An Observational Study during the COVID-19 Outbreak in Shanghai (preprint)

Background:There is a great controversy about lethal effect of Omicron Variant on vulnerable populations and the measure of full-open or zero community transmission policy. Thus, we designed an observational study to evaluate the outcomes of Omicron-infected patients with pancreatic & biliary cancer (the so-called “King of Cancer”) in order to provide potential evidence for the most appropriate strategy to counter Omicron transmission in Shanghai.Methods: Omicron infected patients with advanced pancreatic & biliary cancer were enrolled from April 15 to May 31, 2022. Four groups were set in this study: Group 1, Omicron-infected cancer patients (N=4); Group 2, non-infected cancer patients (N=4); Group 3, infected non-cancer-afflicted subjects (N=4); Group 4, non-infected non-cancer-afflicted subjects (N=4). On Day 0, 7 and 14 after infection, the blood samples were dynamically collected from all subjects. The primary endpoints were disease severity and survival. Results:By the endpoints in this observational study, Patients No. 2, 3 and 4 died separately at Day 11, 25 and 13 after viral infection, all of whom were patients with advanced cancer, with the death rate up to 75%. Group 1 presented an overall T cell exhaustion status compared with other groups with obviously lower T cell populations and higher B cell% and CD4+T/CD8+T ratio (P<0.05). Time-course cytokine monitoring results showed that IL-1β was significantly decreased in Group 1 (P<0.05) and generally kept at a low level without obvious fluctuation. IL-6 was markedly increased in infected cancer patients (P<0.01), but remained a low level and had no apparent change during the whole infection process in non-cancer-afflicted subjects. Furthermore, several inflammatory parameter indexes indicated a tight association of Omicron infection with disease course and prognosis of Omicron-infected cancer patients.Conclusions:For patients with advanced pancreatic & biliary cancer, the strict & comprehensive control strategy for COVID-19 epidemic in Shanghai provided a guarantee of low infection and death rate. Conclusively, this policy shall be persisted upon the consideration of the welfare of vulnerable populations.

Comprehensive narrative review of real-world COVID-19 vaccines: viewpoints and opportunities

Currently, people all over the world have been affected by coronavirus disease 2019 (COVID-19). Fighting against COVID-19 is the top priority for all the countries and nations. The development of a safe and effective COVID-19 vaccine is considered the optimal way of ending the pandemic. Three hundred and 44 vaccines were in development, with 149 undergoing clinical research and 35 authorized for emergency use as to March 15 of 2022. Many studies have shown the effective role of COVID-19 vaccines in preventing SARS-CoV-2 infections as well as serious and fatal COVID-19 cases. However, tough challenges have arisen regarding COVID-19 vaccines, including long-term immunity, emerging COVID-19 variants, and vaccine inequalities. A systematic review was performed of recent COVID-19 vaccine studies, with a focus on vaccine type, efficacy and effectiveness, and protection against SARS-CoV-2 variants, breakthrough infections, safety, deployment and vaccine strategies used in the real-world. Ultimately, there is a need to establish a unified evaluation standard of vaccine effectiveness, monitor vaccine safety and effectiveness, along with the virological characteristics of SARS-CoV-2 variants;and determine the most useful booster schedule. These aspects must be coordinated to ensure timely responses to beneficial or detrimental situations. In the future, global efforts should be directed toward effective and immediate vaccine allocations, improving vaccine coverage, SARS-CoV-2 new variants tracking, and vaccine booster development.

Birds carry a diversity of significant viruses in their virome (preprint)

Birds can carry and transmit viruses to humans and other animals. Thus, understanding the viral community hosted by birds could help us predict future outbreaks of human disease. A recent metagenomics study took a broad look at the viruses found in the gut of wild and captive birds. The dataset included samples from over 3,000 birds that represented over 87 species and 10 different phylogenetic orders and the researchers characterized genomes from numerous viral families including astroviruses, coronaviruses, parvoviruses, and adenoviruses. Examining trends, they found that wild birds had higher viral diversity than captive birds. There was also evidence of potential cross-species transmission between wild birds and domestic poultry. Further analysis of the viral genomic sequences revealed differences in virus distribution patterns between wild and captive birds. Different phylogenetic orders of birds and geographic sites also had distinct distribution patterns. Interestingly, there were no significant differences in virus distribution patterns between migratory and resident birds. While further studies are needed to explore the diversity and potential pathogenicity of these viruses in more detail, this study expanded our understanding of viral diversity in birds.

Global research trends on diseases in the elderly population: a visualization analysis (preprint)

Background Currently, populations around the world are rapidly ageing. Hence, the number of scientific publications on diseases in the elderly population (aged 60 and over) has been expanding.Objective This study aimed to use bibliometric analysis method to illustrate the global research trends over the past 20 years and to summarize the research hotspots that are likely to be addressed in future studies.Methods A literature search for medical publications on diseases in the elderly population in the period from 2000 to 2021 was conducted in the Web of Science Core Collection on April 20, 2022. Visualization analysis was performed using VOSviewer software (version 1.6.16).Results A total of 12,108 publications of the period from 2000 to 2021 were retrieved. The annual publication output grew gradually from 177 in 2000 to 1,236 in 2021. Articles (n = 10,264, 84.77%) were the most common type of documents. The USA issued the largest number of publications (n = 3,632, 30.00%) and had the most citations (citations = 141,230), with the United States Department of Health and Human Services making the largest contribution (n = 1,904, 15.73%). The Lancet had the most citations (citations = 28,548). A total of 545 meaningful topics were identified and further classified into 5 different clusters. The keywords ‘COVID-19’, ‘muscle mass’, ‘depression’ and ‘non-alcoholic fatty liver disease’ have drawn substantial attention in recent years, indicating that these areas will be the centre of attention in future studies on the elderly population.Conclusions This study provides an unbiased visualization analysis of this topic in a scale-efficient manner and includes directions for further research.

Clinical Variables Correlate with Serum Neutralizing Antibody Titers after COVID-19 mRNA Vaccination in an Adult, US-based Population (preprint)

Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population. Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 6 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 91 Veterans and 33 healthcare workers; neutralizing titers were correlated to clinical variables with multivariate regression. In 36 participants, post-booster effect was measured. Results: After completion of the primary vaccine series, neutralizing antibody IC-50 titers were high at one month (14-fold increase from pre-vaccination), declined at six months (3.3-fold increase), and increased at one month post-booster (52.5-fold increase). Age >65 years ({beta}=-0.94, p=0.001) and malignancy ({beta}=-0.88, p=0.002) significantly reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [({beta}=-1.10, p=0.004); ({beta}=-0.66, p=0.014)], diabetes mellitus [({beta}=-0.57, p=0.032); ({beta}=-0.44, p=0.028)], and systemic steroid use [({beta}=-0.066, p=0.032); ({beta}=-0.55, p=0.037)]. Interestingly, the booster neutralizing antibody titer response was unaffected by clinical factors. Conclusion: Multiple clinical factors impacted the strength and duration of post-vaccination serum neutralizing antibodies in this adult population. Response to the booster dose was universally robust, however. This suggests that the antibody response to the booster dose benefits from a sustained and effective anti-Spike memory immune response.

Recent developments and trends of automatic nucleic acid detection systems

Nucleic acid detection, widely used in clinical diagnosis, biological analysis, and environmental monitoring, is of great significance for disease diagnosis and basic research. With the outbreak of COVID-19, the demand for fast and high-throughput nucleic acid detection from large numbers of samples has increased sharply. Automated nucleic acid detection systems can meet these needs, and also play important roles in disease screening and infectious disease prevention and control. In this review, we introduce and compare the current mainstream nucleic acid automatic detection instruments and equipment, then discuss the future demands of nucleic acid detection.

Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617 (preprint)

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ~3 Angstrom resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

Job characteristics and millennial employees’ creative performance: a dual-process model

PurposeBased on previous research on millennial employee management in China, this study aims to extend the understanding of the underlining mechanisms and boundary conditions between job characteristics and millennial employee creative performance. Drawing on the self-determination theory and the theory of situation interaction, this study proposes hedonic and eudaimonic well-being as dual mediators, to explain the positive effect of job characteristics on millennial employees’ creative performance. Further, the study proposes that inclusive leadership and achieving styles could separately moderate these two mediation paths.Design/methodology/approachThe data comprises information on 288 millennial employees in China.FindingsThe results show that both hedonic and eudaimonic well-being mediate the positive effect of job characteristics on millennial employees’ creative performance. The positive effect of job characteristics on millennial employees’ hedonic well-being is stronger when inclusive leadership is stronger;and the positive effect of millennial employees’ hedonic well-being on creative performance is stronger when direct achieving style and instrumental achieving style are stronger. There was no significant moderating effect of inclusive leadership on the relationship between job characteristics and millennial employees’ eudaimonic well-being, and no significant moderating effect of achieving style on the relationship between millennial employees’ eudaimonic well-being and creative performance. Job characteristics exerted a positive indirect effect on employees’ creative performance through employees’ hedonic well-being and that this cascading effect was moderated by inclusive leadership, direct achieving style and instrumental achieving style.Practical implicationsThe findings have important implications for both job design practices and employee performance research. Organizations should pay more attention to improving the creative performance of millennials employees through innovative job design or other organizational level motivational drivers. At the same time, the findings in this study align with the findings in Sheldon et al. (2018) study where extrinsic values rather than toward intrinsic values will bring improved hedonic well-being to the individual in the short term. One further practical implication is that if organizations need a short-term boost of creative performance from their millennial employees, organizations can provide more extrinsic motivators. When organizations want to see more long-term creative performance results, intrinsic motivators should be established.Originality/valueAs part of a series of research on Chinese millennial employee management, this paper extends existing research results. First, the authors verify the main effect relationship between job characteristics and employee creative performance. Second, based on the self-determination theory, this study constructs a dual mediation model and tests the mediating effect of hedonic and eudaimonic well-being between job characteristics and employee creative performance. Third, considering the situational characteristics of the study, the authors propose the boundary conditions of the relationship between job characteristics and creative performance from two levels of individual characteristics and leadership types, namely, inclusive leadership and achieving style.

Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China (preprint)

Background:SARS-CoV-2-caused coronavirus disease (COVID-19) is posinga large casualty. The features of COVID-19patients withand without pneumonia,SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown. Methods: We collected information on clinical characteristics, exposure history, andlaboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020. Results:We characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42(95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to clearance was 9.71(95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared with patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (<190/L) of CD8+ T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 andlactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course,T lymphocytes were generally lower,neutrophils higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocytes did not increase at the 20th days after illness onset. Conclusion: The epidemiological features areimportant for COVID-19 prophylaxis. Circulating interleukin-6 and lactateare independent prognostic factors. CD8+ T cell exhaustion might be critical in the development of COVID-19.