Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants.

Detection of secretory antibodies in the airway is highly desirable when evaluating mucosal protection by vaccines against a respiratory virus, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that intranasal delivery of an attenuated SARS-CoV-2 (Nsp1-K164A/H165A) induces both mucosal and systemic IgA and IgG in male Syrian hamsters. Interestingly, either direct intranasal immunization or airborne transmission-mediated delivery of Nsp1-K164A/H165A in Syrian hamsters offers protection against heterologous challenge with variants of concern (VOCs) including Delta, Omicron BA.1, BA.2.12.1 and BA.5. Vaccinated animals show significant reduction in both tissue viral loads and lung inflammation. Similarly attenuated viruses bearing BA.1 and BA.5 spike boost variant-specific neutralizing antibodies in male mice that were first vaccinated with modified vaccinia virus Ankara vectors (MVA) expressing full-length WA1/2020 Spike protein. Together, these results demonstrate that our attenuated virus may be a promising nasal vaccine candidate for boosting mucosal immunity against future SARS-CoV-2 VOCs.

Vaccination of children in marginalized neighbourhoods: equity and diversity challenges with COVID-19 vaccination campaigns

The coronavirus disease 2019 (COVID-19) pandemic has exacerbated social inequities along ethnic, racial and socio-economic lines, with significant harmful consequences for children. Building on the lessons learned from community-based initiatives, this commentary proposes a reflection around equity, diversity, and inclusion challenges embedded in child vaccination campaigns during an emergency context. We argue that building equitable and inclusive practices around marginalized communities' child vaccination is a multifaceted challenge. Beyond good intentions-wanting to protect children-the risks and benefits associated with highlighting diversity in each intervention need to be carefully considered, especially when it comes to a contested/polarizing procedure such as vaccination with a novel type of vaccine. Often, a one-size-fits-all approach negates and perpetuates structural inequities. In other cases, highlighting diversity and inequities may inadvertently increase stigma and discrimination, and further harm or infantilize targeted communities. By providing multiple perspectives, a transdisciplinary approach can support decision-making in a crisis context.

Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2.

Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC50 ) ≤135 ng/mL against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5, and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma, and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or postvaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses.

Mandating Self-Imposed Curfew - An Analysis of PM Modi's Janta Curfew Speech

This study explores the persuasive strategies used by the Indian Prime Minister (PM) Narendra Modi to appeal to the citizens of India, to observe ‘Janta Curfew’ or People’s Curfew, as a preventive measure to contain the spread of Covid-19 infections in India. The study maps the speech to established strategies and theories of persuasion such as Aristotle’s Rhetorical Triangle, Elaboration Likelihood Model, Monroe's Motivated Sequence, and Cognitive Dissonance Theory;and ascertains the indispensability of the aforementioned theoretical frameworks. The study also identifies Modi’s unique persuasive strategies such as wheedling, building-up (before delivering), complimenting before criticizing, Eutrepismus, and subtly titling the task;and analyzes their effectiveness in persuading the citizens of India to comply with Janta Curfew. Copyright for this article is retained by the author(s)

Intranasal delivery of a rationally attenuated SARS-CoV-2 is immunogenic and protective in Syrian hamsters.

Few live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are in pre-clinical or clinical development. We seek to attenuate SARS-CoV-2 (isolate WA1/2020) by removing the polybasic insert within the spike protein and the open reading frames (ORFs) 6-8, and by introducing mutations that abolish non-structural protein 1 (Nsp1)-mediated toxicity. The derived virus (WA1-ΔPRRA-ΔORF6-8-Nsp1K164A/H165A) replicates to 100- to 1000-fold-lower titers than the ancestral virus and induces little lung pathology in both K18-human ACE2 (hACE2) transgenic mice and Syrian hamsters. Immunofluorescence and transcriptomic analyses of infected hamsters confirm that three-pronged genetic modifications attenuate the proinflammatory pathways more than the removal of the polybasic cleavage site alone. Finally, intranasal administration of just 100 PFU of the WA1-ΔPRRA-ΔORF6-8-Nsp1K164A/H165A elicits robust antibody responses in Syrian hamsters and protects against SARS-CoV-2-induced weight loss and pneumonia. As a proof-of-concept study, we demonstrate that live but sufficiently attenuated SARS-CoV-2 vaccines may be attainable by rational design.

The impact of COVID-19 pandemic and gender-based violence on uptake of HIV services in Touboro District Hospital, Cameroon

As we move towards HIV epidemic control in Cameroon, we strive to limit the number of new infections by maintaining on-treatment PWHIV. The emergence of the Covid-19 pandemic may cause interruptions in HIV treatment and slow progression. COVID-19 control measures have caused;the lockdown of businesses, some health services, and imposed work from home, with intimate partners and more people spending longer hours together at home. As a consequence, there is an increased risk of gender-based violence (GBV). GBV can affect adherence to treatment in PWHIV and prevent them from accessing health services. The main objective of the study was to determine the effect of Covid-19 and GBV on the uptake of HIV services by assessing interruptions in treatment. Using a structured questionnaire, demographic data, Information on COVID-19 and intimate partner violence were obtained from 339 participants between 15 and 60 years old, taking HIV treatment at the Touboro district hospital. We used the Antiretroviral treatment register of the health facility to extract data on the frequency and duration of interruption in treatment. The Prevalence of intimate partner violence was high in our study participants, although interruption in treatment was only significant in respondents who reported verbal abuse. A strong association was observed between Covid 19 and interruption in treatment. There was equally an association between Covid-19 and an increase in intimate IPV. Other Socio-demographic variables found to affect interruption in treatment were level of Education of the partner, Age difference with intimate partner greater than 10 years, and early years on antiretroviral therapy. According to the study, Both Gender-based violence (IPV) and Covid-19 affect interruption in antiretroviral treatment.

An international, interlaboratory ring trial confirms the feasibility of an extraction-less "direct" RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). "Extraction-less" or "direct" real time-reverse transcription polymerase chain reaction (RT-PCR) is a transparent and accessible qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that direct RT-PCR assay methods can be clearly translated across sites utilizing readily available equipment and expertise and are thus a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.

Membrane-Based In-Gel Loop-Mediated Isothermal Amplification (mgLAMP) System for SARS-CoV-2 Quantification in Environmental Waters.

Since the COVID-19 pandemic is expected to become endemic, quantification of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambient waters is critical for environmental surveillance and for early detection of outbreaks. Herein, we report the development of a membrane-based in-gel loop-mediated isothermal amplification (mgLAMP) system that is designed for the rapid point-of-use quantification of SARS-CoV-2 particles in environmental waters. The mgLAMP system integrates the viral concentration, in-assay viral lysis, and on-membrane hydrogel-based RT-LAMP quantification using enhanced fluorescence detection with a target-specific probe. With a sample-to-result time of less than 1 h, mgLAMP successfully detected SARS-CoV-2 below 0.96 copies/mL in Milli-Q water. In surface water, the lowest detected SARS-CoV-2 concentration was 93 copies/mL for mgLAMP, while the reverse transcription quantitative polymerase chain reaction (RT-qPCR) with optimal pretreatment was inhibited at 930 copies/mL. A 3D-printed portable device is designed to integrate heated incubation and fluorescence illumination for the simultaneous analysis of nine mgLAMP assays. Smartphone-based imaging and machine learning-based image processing are used for the interpretation of results. In this report, we demonstrate that mgLAMP is a promising method for large-scale environmental surveillance of SARS-CoV-2 without the need for specialized equipment, highly trained personnel, and labor-intensive procedures.

MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge.

Numerous vaccine candidates against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are under development. The majority of vaccine candidates to date are designed to induce immune responses against the viral spike (S) protein, although different forms of S antigen have been incorporated. To evaluate the yield and immunogenicity of different forms of S, we constructed modified vaccinia virus Ankara (MVA) vectors expressing full-length S (MVA-S), the RBD, and soluble S ectodomain and tested their immunogenicity in dose-ranging studies in mice. All three MVA vectors induced spike-specific immunoglobulin G after one subcutaneous immunization and serum titers were boosted following a second immunization. The MVA-S and MVA-ssM elicited the strongest neutralizing antibody responses. In assessing protective efficacy, MVA-S-immunized adult Syrian hamsters were challenged with SARS-CoV-2 (USA/WA1/2020). MVA-S-vaccinated hamsters exhibited less severe manifestations of atypical pneumocyte hyperplasia, hemorrhage, vasculitis, and especially consolidation, compared to control animals. They also displayed significant reductions in gross pathology scores and weight loss, and a moderate reduction in virus shedding was observed post challenge in nasal washes. There was evidence of reduced viral replication by in situ hybridization, although the reduction in viral RNA levels in lungs and nasal turbinates did not reach significance. Taken together, the data indicate that immunization with two doses of an MVA vector expressing SARS-CoV-2 S provides protection against a stringent SARS-CoV-2 challenge of adult Syrian hamsters, reaffirm the utility of this animal model for evaluating candidate SARS-CoV-2 vaccines, and demonstrate the value of an MVA platform in facilitating vaccine development against SARS-CoV-2.

Determinants of the Economic Vulnerability of Businesses to Pandemics and Similar Events

After providing a general overview of factors that make businesses economically vulnerable to pandemics (such as COVID-19), this article identifies specific elements that increase the vulnerability of businesses to pandemics. These specifics include the extent to which the demand for their production declines, how easy it is for them to reduce the costs of their production (cost escapability), the importance of disruptions or breaks in the supply chains of inputs utilized by businesses, and their ability to sustain their liquidity. Businesses that rely on personal contacts for sales are especially threatened, for example, those in the hospitality and tourism sector. However, others are also vulnerable for the reasons given. Nevertheless, some businesses do gain as a result of pandemics and similar events. Their economic gain adds to GDP. However, it could be more appropriate to regard their gains as a part of the cost of a pandemic rather than a benefit of it. The effect on the vulnerability of businesses if government policies designed to control pandemics is also considered. The main original contribution of this article is to show how the microeconomic theory of the firm can be adapted to conceptualize the vulnerability of individual businesses to pandemics, particularly COVID-19, while also noting the limitations of this approach.

Instructor-Led Teaching Versus E-Learning: Challenges and Opportunities

During and after the Covid-19-induced lockdown, online teaching has attained an unprecedented status like never before all over the world. Teachers and students have been compelled to fall in line with the new normal of virtual classrooms. Even though many teachers and students have expressed their inconvenience of virtual classrooms, it has become mandatory to adapt their teaching and learning styles to cope with the exasperating times triggered by the coronavirus. The survey presented in this paper was conducted among second and third-year engineering students of a private university in India just before the Covid-19 outbreak. The objective of the survey was to understand which method is more suitable for learning English skills for the engineering students. The students' attitude and perception toward online and teacher-led sessions have been unveiled through qualitative and quantitative data. The participants have weighed the pros and cons of both the methods according to their specific needs, and the results suggest that in order to have a balanced teaching-learning process, the students require both the methods. It has been identified that students' needs play a major role while choosing between online or teacher-led sessions. Though the modern generation relies more on technology, teacher-led sessions have not lost the sheen and are considered an effective way of learning due to various factors such as human interaction, direct guidance, and knowledge-sharing possibilities.

An international, inter-laboratory ring trial confirms the feasibility of an open source, extraction-less "direct" RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples (preprint)

RT-qPCR is used world-wide to test and trace the spread of SARS-CoV-2. Extraction-less or direct RT-PCR is an open-access qualitative method for SARS-CoV-2 detection from nasopharyngeal (NP) or oral pharyngeal (OP) samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged ten global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international inter-laboratory ring trial. Participating labs were provided a common protocol, common reagents, aliquots of identical pooled clinical samples and purified nucleic acids, and used their existing in-house equipment. We observed 100% concordance across labs in the correct identification of all positive and negative samples, with highly similar Ct values observed. The test also performed well when applied to locally collected patient NP samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that open access, direct RT-PCR assays are a feasible option for more efficient COVID-19 testing as demanded by the continuing pandemic.

Economic, social and political issues raised by the COVID-19 pandemic.

This article contributes to the assessment of public policies to control the incidence of COVID-19 in several ways. (1) It contains a brief historical and comparative overview of selected pandemics, particularly in relation to the COVID-19 pandemic; (2) It provides a simple original model which could be used to prioritize the admission of COVID-19 sufferers to hospital (taking into account available hospital capacity) and (3) it specifies a second model to evaluate desired social choices involving the trade-off between the severity of social restrictions (taking into account their impact on the incidence of COVID-19) and the level of economic activity. Bergson-type welfare functions are utilized in the second model. It also critically examines the proposition that the isolation (lockdown) of social groups is a desirable method of limiting the incidence of COVID-19. This leads onto the consideration of the extent to which personal freedom of choice (liberty) ought to be restricted in response to the COVID-19 pandemic. A brief outline follows illustrating the factors that are likely to hinder economic recovery from COVID-19. Particular attention is paid to the moral and ethical questions raised by policies to control COVID-19. These appear to have received little attention in the relevant economic literature.

The potential of putative zinc-binding motifs of haemagglutinin (HA) protein for categorization and prediction of pathogenicity of H5 subtypes of avian influenza virus.

In the present study, we used the potential of bioinformatics and computational analysis to predict the existence and biological relevance of zinc finger (ZF) motifs in heamagglutinin (HA) protein of Avian Influenza (AI) virus. Sequence data of Avian Influenza (AI) viruses were retrieved from accessible databases (GenBank, GISAID, IRD) and analyzed for the existence, as well as functional prediction of the putative zinc finger or ''zinc-binding'' motif(s) of HA protein. It is hypothesized that the ZF motif(s) in HA of AI virus can be used as a ''novel'' biomarker for categorization of the virus and/or its virulence. As a model for analysis, we used the H5 subtypes of highly pathogenic, non-pathogenic and low pathogenic avian influenza (HPAI, NPAI and LPAI) viruses of H5N1 and H5N2 of avian and human origins. Interestingly, our method of characterization using the zinc-finger agrees with the existing classification in distinguishing between highly pathogenic and non-pathogenic or low pathogenic subtypes. The new method also clearly distinguished between low and non-pathogenic strains of H5N2 and H5N1 which are indistinguishable by the existing method that utilizes the sequence of the polybasic amino acids of the proteolytic cleavage site for pathogenicity. It is hypothesized that zinc through the activities of zinc-binding proteins modulates the virulence property of the viral subtypes. Our observation further revealed that only the HA protein among the eight encoded proteins of influenza viruses contain high numbers of Cys-His residues. It is expected that the information gathered from the analysis of the data will be useful to generate more research hypotheses/designs that will give further insight towards the identification and control of avian influenza virus through the molecular manipulation of zinc finger motifs present in viral HA protein.