Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant.

The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.

Chest CT and Hospital Outcomes in Patients with Omicron Compared with Delta Variant SARS-CoV-2 Infection.

Background The SARS-Cov-2 Omicron variant demonstrates rapid spread but with reduced disease severity. Studies evaluating the lung imaging findings of Omicron infection versus non-Omicron variants remain lacking. Purpose To compare Omicron and Delta variants of SARS-CoV-2 by their chest CT radiological pattern, biochemical parameters, clinical severity and hospital outcomes after adjusting for vaccination status. Materials and Methods Retrospective study of hospitalized adult patients rt-PCR positive for SARS-CoV-2 with CT pulmonary angiography performed within 7 days of admission between December 1, 2021 and January 14, 2022. Blinded radiological analysis with multiple readers including RSNA CT classification, chest CT severity score (CT-SS, range 0 least severe to 25 most severe) and CT imaging features including bronchial wall thickening. Results 106 patients (Delta n=66, Omicron n=40) were evaluated (mean age, 58 years ± 18, 58 men). In the Omicron group, 37% (15/40) of CT pulmonary angiograms were categorized as normal compared with 15% (10/66) in the Delta group (p=.016). Using a generalized linear model to control for confounding variables, including vaccination status, Omicron variant infection was associated with a CT-SS that was lower by 7.2 points compared to infection with Delta variant (ß=-7.2, 95%CI: -9.9, -4.5; p <.001). Bronchial wall thickening was more common with Omicron than with the Delta variant (odds ratio [OR] 2.4, 95%CI: 1.01, 5.92, p=.04). Vaccination with a booster shot was associated with a protective effect on chest infection compared with the unvaccinated (CT-SS median 5 (IQR 0-11), CT-SS median 11 (IQR 7.5-14), respectively; p = .03). The Delta variant was associated with a higher odds ratio of severe disease (OR 4.6, 95%CI: 1.2, 26, p=.01) and critical care admission (OR 7.0, 95%CI: 1.5, 66, p=.004) than the Omicron variant. Conclusion The SARS-COV-2 Omicron variant was associated with fewer and less severe changes on chest CT compared with the Delta variant. Patients with Omicron had greater frequency of bronchial wall thickening but lower clinical severity and improved hospital outcomes than those with Delta.

Covid-19, and the climate change and biodiversity emergencies.

This paper addresses the question, can lessons be learnt by studying the responses to COVID-19 and the human-induced climate change and loss of biodiversity emergencies? It is well recognized that to successfully address each of these issues requires sound scientific knowledge based on strong national and international research programs, cooperation between the research community and policy makers, national, regional and global evidence-based policies and coordinated actions, an informed and receptive public, and political will. A key question is how research and innovation can most effectively inform decision-making leading to cost-effective and socially acceptable action on pandemics, climate change and loss of biodiversity. This paper first describes how the COVID-19 pandemic has been addressed compared to the loss of biodiversity, and climate change, and then considers the use of scientific knowledge for policy-making and communication with the public. The paper then discusses human health and the natural environment as a global responsibility, and concludes on the need for an enhanced virtuous set of interactions between science, economy, politics and people.

Activity of a Carbohydrate-Binding Module Therapy, Neumifil, against SARS-CoV-2 Disease in a Hamster Model of Infection.

The rapid global spread of severe acute respiratory coronavirus 2 (SARS-CoV-2) has resulted in an urgent effort to find efficacious therapeutics. Broad-spectrum therapies which could be used for other respiratory pathogens confer advantages, as do those based on targeting host cells that are not prone to the development of resistance by the pathogen. We tested an intranasally delivered carbohydrate-binding module (CBM) therapy, termed Neumifil, which is based on a CBM that has previously been shown to offer protection against the influenza virus through the binding of sialic acid receptors. Using the recognised hamster model of SARS-CoV-2 infection, we demonstrate that Neumifil significantly reduces clinical disease severity and pathological changes in the nasal cavity. Furthermore, we demonstrate Neumifil binding to the human angiotensin-converting enzyme 2 (ACE2) receptor and spike protein of SARS-CoV-2. This is the first report describing the testing of this type of broad-spectrum antiviral therapy in vivo and provides evidence for the advancement of Neumifil in further preclinical and clinical studies.

Consumer Risk Perceptions, Behavioral Intentions, and Purchasing Habits toward Delivery Apps

In this article, I cumulate previous research findings indicating that continuance intention and performance expectancy of food delivery apps shape risk perception in relation to COVID-19. I contribute to the literature on consumer risk perceptions, behavioral intentions, and purchasing habits toward delivery apps by showing that behavioral emotions and purchasing choices, decisions, and habits configure food delivery ordering experience by use of mobile apps. Throughout January 2022, I performed a quantitative literature review of the Web of Science, Scopus, and ProQuest databases, with search terms including "delivery app" + "consumer risk perception," "behavioral intention," and "purchasing habit." As I inspected research published in 2020 and 2021, only 147 articles satisfied the eligibility criteria. By eliminating controversial findings, outcomes unsubstantiated by replication, too imprecise material, or having similar titles, I decided upon 23, generally empirical, sources. Reporting quality assessment tool: PRISMA. Methodological quality assessment tools include: AXIS, Dedoose, ROBIS, and SRDR.

Influence of Aerosol Delivered BCG Vaccination on Immunological and Disease Parameters Following SARS-CoV-2 Challenge in Rhesus Macaques

The tuberculosis vaccine, Bacille Calmette-Guerin (BCG), also affords protection against non-tuberculous diseases attributable to heterologous immune mechanisms such as trained innate immunity, activation of non-conventional T-cells, and cross-reactive adaptive immunity. Aerosol vaccine delivery can target immune responses toward the primary site of infection for a respiratory pathogen. Therefore, we hypothesised that aerosol delivery of BCG would enhance cross-protective action against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and be a deployable intervention against coronavirus disease 2019 (COVID-19). Immune parameters were monitored in vaccinated and unvaccinated rhesus macaques for 28 days following aerosol BCG vaccination. High-dose SARS-CoV-2 challenge was applied by intranasal and intrabronchial instillation and animals culled 6–8 days later for assessment of viral, disease, and immunological parameters. Mycobacteria-specific cell-mediated immune responses were detected following aerosol BCG vaccination, but SARS-CoV-2-specific cellular- and antibody-mediated immunity was only measured following challenge. Early secretion of cytokine and chemokine markers associated with the innate cellular and adaptive antiviral immune response was detected following SARS-CoV-2 challenge in vaccinated animals, at concentrations that exceeded titres measured in unvaccinated macaques. Classical CD14+ monocytes and Vδ2 γδ T-cells quantified by whole-blood immunophenotyping increased rapidly in vaccinated animals following SARS-CoV-2 challenge, indicating a priming of innate immune cells and non-conventional T-cell populations. However, viral RNA quantified in nasal and pharyngeal swabs, bronchoalveolar lavage (BAL), and tissue samples collected at necropsy was equivalent in vaccinated and unvaccinated animals, and in-life CT imaging and histopathology scoring applied to pulmonary tissue sections indicated that the disease induced by SARS-CoV-2 challenge was comparable between vaccinated and unvaccinated groups. Hence, aerosol BCG vaccination did not induce, or enhance the induction of, SARS-CoV-2 cross-reactive adaptive cellular or humoral immunity, although an influence of BCG vaccination on the subsequent immune response to SARS-CoV-2 challenge was apparent in immune signatures indicative of trained innate immune mechanisms and primed unconventional T-cell populations. Nevertheless, aerosol BCG vaccination did not enhance the initial clearance of virus, nor reduce the occurrence of early disease pathology after high dose SARS-CoV-2 challenge. However, the heterologous immune mechanisms primed by BCG vaccination could contribute to the moderation of COVID-19 disease severity in more susceptible species following natural infection.

Sequential Delivery of Live Attenuated Influenza Vaccine and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the Ferret Model Can Reduce SARS-CoV-2 Shedding and Does Not Result in Enhanced Lung Pathology.

Cocirculation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses could pose unpredictable risks to health systems globally, with recent studies suggesting more severe disease outcomes in coinfected patients. The initial lack of a readily available coronavirus disease 2019 (COVID-19) vaccine has reinforced the importance of influenza vaccine programs during the COVID-19 pandemic. Live attenuated influenza vaccine (LAIV) is an important tool in protecting against influenza, particularly in children. However, it is unknown whether LAIV administration influences the outcomes of acute SARS-CoV-2 infection or disease. To investigate this, quadrivalent LAIV was administered to ferrets 3 days before or after SARS-CoV-2 infection. LAIV administration did not exacerbate the SARS-CoV-2 disease course or lung pathology with either regimen. In addition, LAIV administered before SARS-CoV-2 infection significantly reduced SARS-CoV-2 replication and shedding in the upper respiratory tract. This study demonstrated that LAIV administration in close proximity to SARS-CoV-2 infection does not exacerbate mild disease and can reduce SARS-CoV-2 shedding.

The Impact of the COVID-19 Pandemic on Consumer Satisfaction Judgments, Behavior Patterns, and Purchase Intentions

Employing recent research results covering consumer satisfaction judgments, behavior patterns, and purchase intentions during the COVID-19 pandemic, and building our argument by drawing on data collected from AlixPartners, Criteo, Deloitte, and McKinsey, we performed analyses and made estimates regarding how the COVID-19 pandemic may alter food purchases and retail grocery sales permanently, influencing consumers to adopt sustainable shopping behaviors and thus possibly improving their satisfaction and quality of life. Descriptive statistics of compiled data from the completed surveys were calculated when appropriate.

Will the COVID-19 Pandemic Lead to Long-Term Consumer Perceptions, Behavioral Intentions, and Acquisition Decisions?

Despite the relevance of possible long-term consumer perceptions, behavioral intentions, and acquisition decisions related to the COVID-19 pandemic, only limited research has been conducted on this topic. Using and replicating data from Accenture, KPMG, and McKinsey, we performed analyses and made estimates regarding how the COVID-19 pandemic has reshaped customer attitudes, behaviors, values, and expectations, reconfiguring consumer traits, sentiments, trust, and engagement, and thus leading to altered purchasing decisions and habits, and buying patterns in terms of psychological risk perception. The results of a study based on data collected from 9,200 respondents provide support for our research model. Descriptive statistics of compiled data from the completed surveys were calculated when appropriate.

An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Development of a Hamster Natural Transmission Model of SARS-CoV-2 Infection.

The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection.

A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19.

SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately, effective prophylaxis. The molecule was similarly potent by intraperitoneal injection.

ChAdOx1 nCoV-19 protection against SARS-CoV-2 in rhesus macaque and ferret challenge models.

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

One or two dose regimen of the SARS-CoV-2 synthetic DNA vaccine INO-4800 protects against respiratory tract disease burden in nonhuman primate challenge model.

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 106 pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.

Implementing An Active Learning, Large-Enrollment Online Physiology Course During The COVID-19 Pandemic

The Department of Neurobiology & Behavior at Stony Brook University offers a large-enrollment gateway undergraduate physiology course, BIO 203 - Fundamentals of Biology: Cellular and Organ Physiology. BIO 203 is a required course in the biology and biochemistry majors and in the pre-health curriculum, and undergraduates typically register for BIO 203 in their sophomore year. Since Fall 2015, BIO 203 has been offered in two formats, traditional PowerPoint-based lectures presented twice per week (80 min / session) in a 570-seat auditorium with individual fixed seats and a flipped, active-learning format delivered once per week (113 min / session) in a 250-seat auditorium with shared desks and rotating chairs. Students in both sections had equal access to prerecorded lectures and online activities (content quizzes, journal activities and thought questions). The focus of the lecture section was content delivery while the flipped section emphasized active group learning facilitated by instructors and experienced undergraduate teaching assistants. Student learning was evaluated by performance on common high-stakes multiple choice exams. On average, students in the flipped section exhibited better performance on the common exams than students in the lecture section (Fall 2019 exam total, p < 0.05 in two sample t test and Wilcoxon rank sum test). As a result of the COVID-19 pandemic, Stony Brook University required large-enrollment courses to switch to online instruction starting in March 2020 and continuing through the Fall 2020 semester. The BIO 203 instructors implemented a synchronous online version of BIO 203 based on the active-learning curriculum developed for the flipped section. In Fall 2020, this synchronous online version of BIO 203 was offered simultaneously to two sections. Students in both sections had access to the same online resources (recorded lectures, content quizzes and activities) and were evaluated using low-stakes quizzes (administered during scheduled class time) and a common cumulative final exam (administered during a common final exam period). The primary difference between the two sections was the frequency and duration of the synchronous online meetings with instructors and teaching assistants. Section 01 (595 students) met twice a week for 80 min per session, whereas section 02 (257 students) met once a week for 130 min. A preliminary analysis of the scores on the common final exam indicates that students in section 01 (two meetings per week) performed better than students in section 02 (1 meeting per week) (p < 0.05 in two sample t test and Wilcoxon rank sum test). These preliminary findings are consistent with the hypothesis that student learning is enhanced by frequent engagement in active learning.

Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19.

A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques. Immune responses against SARS-CoV-2 are also similar in both species and equivalent to those reported in milder infections and convalescent human patients. This finding is reiterated by our transcriptional analysis of respiratory samples revealing the global response to infection. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the preferred study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of interventions against SARS-CoV-2. Importantly, accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.

Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity.

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.