Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data

BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHOD(S): We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40.0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1.0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi.Copyright © 2023 Elsevier Ltd. All rights reserved.

Creating a Virtual Learning Environment for Increasing Awareness of Blockchain Technologies at a Minority Serving Institution

In this paper, we describe the successful implementation of a virtual learning environment for an immersive blockchain workshop that was designed to increase awareness, cultivate collaboration, and build technical knowledge in Blockchain technologies for participants in minority-serving academic engineering and computer science communities. In the pre-covid world, the authors meticulously designed an immersive two-day technical workshop on Blockchain technologies for engineering and computer science communities in efforts to increase awareness and cultivate interdisciplinary collaborations among researchers at an historically black university. When the covid-19 pandemic disrupted our lives on a global scale, the authors contemplated canceling the event completely. However, understanding the significance of Blockchain as an emerging technology and knowing how important this knowledge is to the advancement of education in minority communities, the authors made the executive decision to host a completely virtual workshop event. The primary goals of the virtual Blockchain workshop did not change. They were: (1) to provide an immersive environment for participants to learn about Blockchain technologies;(2) to cultivate networking and collaborations among faculty and students in Blockchain;and (3) to stimulate interest and awareness of Blockchain and Fintech research in engineering and computer science departments at the minority-serving institution (MSI). However, the authors had to rethink and redesign a completely virtual, online event. How can we make the learning environment engaging? How can we make the learning environment collaborative? How can we ensure that instruction is effective and meaningful for participants? How can we recruit students to participate in this informal online educational enrichment activity? These were some of the questions that the authors considered when redesigning the Blockchain workshop. The workshop redesign included three main design elements: a leadership team;an immersive blockchain curriculum design, and fun and engaging enrichment activities including online games and a networking café. The program success was determined using seven key indicators such as (1) the total number of registrants;(2) the number of attendees who completed the 1st session and earned badge;(3) the number of attendees who received two badges at the end of the workshop;(4) number of attendees who were able to network with one another either in-person or in virtual breakout rooms;(5) percentage of faculty participants who have intentions to incorporate Blockchain into their instructional design;(6) percentage of faculty participants who have intentions to incorporate Blockchain into their research efforts;(7) percentage of participants whose interest in Blockchain increased as a result of this workshop. Based on the results, target achievements were met or exceeded in all performance metrics except two, key indicators 3 and 5. Evidence suggests that these targets were not met due to hardware installation issues and faculty engagement. The main contribution of this work is the discovery of how to pivot from in-person learning to effective online learning through the design, adaptation and implementation of educational enrichment workshops in a virtual academic setting post the covid-19 pandemic. © American Society for Engineering Education, 2022.

Social media in neurosurgery during COVID-19: an evaluation of the role of Neurosurgery Cocktail platform.

BACKGROUND: Social media use in neurosurgery remains an understudied phenomenon. Our study aims to examine the global membership and engagement of the prominent Neurosurgery Cocktail Facebook group with over 25,000 neurosurgeons and trainees worldwide, specifically during the COVID-19 pandemic. METHODS: Neurosurgery Cocktail's numbers of members, posts, comments, and reactions were collected from December 2019 to November 2020. Anonymized aggregate data of members' characteristics, including age, sex, and country of origin in November 2020, were also obtained. The most engaging posts in November 2020 were categorized into topics by a majority consensus of 3 reviewers. RESULTS: The average number of members steadily increased from 21,266 in December 2019 to 25,218 in November 2020. In November 2020, 18.8% of members were women, and 71.3% were between 25-44 years old. With members from 100 countries, 77.9% are from low-and middle-income countries, with the highest representation from India, Egypt, and Brazil. After the COVID-19 pandemic declaration, daily engagement peaked in April 2020 with a daily average of 41.63 posts, 336.4 comments, and 1,914.6 reactions before returning to prepandemic levels. Among the 99 top posts in November 2020, the majority (56.5%) were classified as "interesting cases", with "education-related" as the second-most common topic (16.2%). CONCLUSIONS: Neurosurgery Cocktail has shown steady growth since its creation. The COVID-19 pandemic was correlated with a spike in activity without lasting impact. The group demonstrates social media's potential for knowledge exchange and promoting organic international collaborations.

Applying Machine Learning to Analyze Anti-Vaccination on Tweets

Inspection of Anti-COVID vaccination tweets can be useful for many such analyses, and extraction of relevant information about opinion expressed on Twitter. This study proposes an analytical framework for analyzing tweets (COVID Vaccine, especially the Anti- COVID Vaccine) to identify and categorize fine-grained details about the COVID19 disaster such as affected individuals, public feelings towards the vaccine and reopening of business, polarity of public opinions on the vaccine and services provided, discussed topic changing over temporal dimension, and different clustering algorithms. In this project, we have analyzed COVID -Vaccine related tweets and Anti-Vaccine tweets, performed sentiment analysis and Topic modeling, and compared various models' behavior based on different configuration and training datasets. The result of this work will help policy makers and data scientists to identify the best approach for twitter sentiment analysis and topic modeling as well as providing feedback on people attitude and opinion on COVID-19 vaccine. © 2021 IEEE.

Survival strategies of the sharing economy from the pandemic to a new normal: A dynamic capabilities approach

This paper explores the business strategies of car-sharing platforms between 2020 and 2021, during the COVID-19 pandemic. The study conducted a systematic review and adopted a dynamic capabilities approach;it analyzes 231 online articles concerning Uber, Ola, and Grab to demonstrate 6S sub-constructs: SAFETY, SCAN, SYSTEM, SUPPORT, SPREAD, and SPEED. The findings suggest that developing safe riding experiences, identifying threats through technology, realigning culture/structure through financial/community support, and expanding delivery services are necessary strategies to combat the pandemic. The new normal has managerial and policy implications on how businesses in the sharing economy sector adapt to radical and dynamic environments. © 2022 John Wiley & Sons, Ltd.

The role of perceived workplace safety practices and mindfulness in maintaining calm in employees during times of crisis

While prior studies in human resource management have investigated how employee outcomes have been affected in high-risk workplaces, this study stands out by examining this issue through the role played by COVID-19 as a specific stressor. We explained how employees' perceived health risks due to COVID-19 (CV19PHR) and perceived workplace safety practices (PWSPs) affected job performance via burnout and how PWSPs moderated the CV19PHR-burnout and CV19PHR-JP relationships. We also examined how mindfulness moderated the direct effects of CV19PHR and PWSPs on burnout and JP and the indirect effects of CV19PHR and PWSPs on JP via burnout. We performed three studies using an explanatory sequential mixed-method design. In study 1, a three-phase survey with 987 respondents was conducted to test the hypotheses. In study 2, by analyzing verbatim from 22 informants, the findings of study 1 and some main points concerning mindfulness and PWSPs were explained. In study 3, using data from 12 informants, we investigated how COVID-19 affected individuals differently compared with other high-risk workplaces and whether the impact of COVID-19 on individuals was curvilinear. We demonstrated that employees' CV19PHR was positively correlated with burnout, negatively influencing JP. Moreover, PWSPs reduced burnout, which adversely affected JP. Interestingly, PWSPs positively moderated the CV19PHR-burnout relationship but not the CV19PHR-JP relationship. We also found that mindfulness moderated the CV19PHR-burnout and PWSPs-burnout relationships. Furthermore, mindfulness significantly moderated the mediating effects of burnout on the CV19PHR-JP and PWSPs-JP relationships.

Long-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection.

BACKGROUND: The duration of immunity in SARS-CoV-2 infected people remains unclear. Neutralizing antibody responses are the best available correlate of protection against re-infection. Recent studies estimated that the correlate of 50% protection from re-infection was 20% of the mean convalescent neutralizing antibody titre. METHODS: We collected sera from a cohort of 124 individuals with RT-PCR confirmed SARS-CoV-2 infections from Prince of Wales Hospital, Princess Margaret Hospital, Queen Elizabeth Hospital and Queen Mary Hospitals of the Hospital Authority of Hong Kong, for periods up to 386 days after symptom onset and tested these for antibody to SARS-CoV-2 using 50% virus plaque reduction neutralization tests (PRNT50), surrogate neutralization tests and spike receptor binding domain (RBD) binding antibody. Patients were recruited from 21 January 2020 to 16 February 2021 and follow-up samples were collected until 9th March 2021. FINDINGS: Because the rate of antibody waning slows with time, we fitted lines of decay to 115 sera from 62 patients collected beyond 90 days after symptom onset and estimate that PRNT50 antibody will remain detectable for around 1,717 days after symptom onset and that levels conferring 50% protection will be maintained for around 990 days post-symptom onset, in symptomatic patients. This would potentially be affected by emerging virus variants. PRNT titres wane faster in children. There was a high level of correlation between PRNT50 antibody titers and the % of inhibition in surrogate virus neutralization tests. INTERPRETATION: The data suggest that symptomatic COVID-19 disease is followed by relatively long-lived protection from re-infection by antigenically similar viruses. FUNDING: Health and Medical Research Fund, Commissioned research on Novel Coronavirus Disease (COVID-19) (Reference Nos. COVID190126 and COVID1903003) from the Food and Health Bureau and the Theme-based Research Scheme project no. T11-712/19-N, the University Grants Committee of the Hong Kong SAR Government.

Direct Activation of Endothelial Cells by SARS-CoV-2 Nucleocapsid Protein Is Blocked by Simvastatin.

Emerging evidence suggests that endothelial activation plays a central role in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan failure in patients with coronavirus disease 2019 (COVID-19). However, the molecular mechanisms underlying endothelial activation in COVID-19 patients remain unclear. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins that potently activate human endothelial cells were screened to elucidate the molecular mechanisms involved in endothelial activation. It was found that nucleocapsid protein (NP) of SARS-CoV-2 significantly activated human endothelial cells through Toll-like receptor 2 (TLR2)/NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Remarkably, though the protein sequences of N proteins from coronaviruses are highly conserved, only NP from SARS-CoV-2 induced endothelial activation. The NPs from other coronaviruses such as SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), HUB1-CoV, and influenza virus H1N1 did not activate endothelial cells. These findings are consistent with the results from clinical investigations showing broad endotheliitis and organ injury in severe COVID-19 patients. In conclusion, the study provides insights on SARS-CoV-2-induced vasculopathy and coagulopathy and suggests that simvastatin, an FDA-approved lipid-lowering drug, may help prevent the pathogenesis and improve the outcome of COVID-19 patients. IMPORTANCE Coronavirus disease 2019 (COVID-19), caused by the betacoronavirus SARS-CoV-2, is a worldwide challenge for health care systems. The leading cause of mortality in patients with COVID-19 is hypoxic respiratory failure from acute respiratory distress syndrome (ARDS). To date, pulmonary endothelial cells (ECs) have been largely overlooked as a therapeutic target in COVID-19, yet emerging evidence suggests that these cells contribute to the initiation and propagation of ARDS by altering vessel barrier integrity, promoting a procoagulative state, inducing vascular inflammation and mediating inflammatory cell infiltration. Therefore, a better mechanistic understanding of the vasculature is of utmost importance. In this study, we screened the SARS-CoV-2 viral proteins that potently activate human endothelial cells and found that nucleocapsid protein (NP) significantly activated human endothelial cells through TLR2/NF-κB and MAPK signaling pathways. Moreover, by screening a natural microbial compound library containing 154 natural compounds, simvastatin was identified as a potent inhibitor of NP-induced endothelial activation. Our results provide insights on SARS-CoV-2-induced vasculopathy and coagulopathy, and suggests that simvastatin, an FDA-approved lipid-lowering drug, may benefit to prevent the pathogenesis and improve the outcome of COVID-19 patients.

[Suggestions on reforming and improving the prevention and treatment system for major epidemic diseases in China].

Based on systematic review of the role of clinical treatment, disease control and scientific research, and combining with the problems exposed by the COVID-19 epidemic, suggestions were proposed to reform and improve the prevention and treatment system for major epidemics diseases in China. In clinical treatment, it is necessary to enhance clinical staff's awareness of law-based reporting, capabilities of syndromic surveillance, the use of infectious diseases reporting systems, and to improve national or local monitoring platforms for emerging infectious diseases detection. In terms of disease control, it is important to provide authorities to disease control departments through laws and regulations, improve the quantity and quality of related human resources, and strengthen the applied research and technical readiness targeted infections disease prevention, control and emergency preparedness. As for scientific research in major epidemic response, it is essential to strengthen research projects guided by national requests, build research institutions that can "make a final decision" , establish national and regional key laboratories, and strengthen strategic technical reserve for emergency disease control and treatment.

Experimenting with At-Home General Chemistry Laboratories During the COVID-19 Pandemic

During the COVID-19 pandemic, an at-home laboratory program was created and implemented for a section of the general chemistry course at the University of Southern California. The experiments were designed to only utilize safe household items and no special equipment. These laboratory activities, spanning over 4 weeks, focused on concepts usually covered in the final one-third of our second-semester chemistry laboratory, including pH, acid-base titrations, buffers, solubility, phase equilibria, and thermodynamics. In this article, we describe the design of the laboratories and our experience with this experiment, while also providing an assessment on how similar activities could be integrated profitably into a regular general chemistry course.