Applying the principles of triage to support the rapid transition to online learning during the pandemic

In the higher education sector, military academies operate in environments that differ from university campuses. Like other institutions, military academies had to manage changes to learning and teaching in response to the COVID-19 pandemic. This required an approach, a model, that acknowledges and aligns with the needs of a military academy. Using a case study approach, the changes at one faculty at an Australian military academy undergoing a rapid transition to online learning are outlined and evaluated using both survey and unobtrusive data. The changes were framed by a new 3S triage model of see, solve and share, specifically designed for the context of the military academy. Distributed leadership approach and its 6E theoretical tenets are used to detail the model’s application, the role of policy, and positive outcomes, including an increase in student satisfaction.

A New Direction? The Arts and Central Government Policy in Aotearoa New Zealand, 2017-2020

Artistic work in Aotearoa has long been underpaid and undervalued. In this paper, we examine policy statements made by the New Zealand government from September 2017 until November 2020 about the nature and value of artistic work. Early statements appear to challenge the economization of the arts, and to suggest alternative ways the arts might be valued, including for their inherent connection to well-being and social justice. However, rather than moving the arts away from commercial imperatives, we argue that government initiatives have been implicitly equipping artists and arts organizations to deliver their own economization.

Antibody Profiling in COVID-19 Patients with Different Severities by Using Spike Variant Protein Microarrays.

The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.

Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine.

The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 µg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 µg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 µg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 µg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 µg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-µg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 µg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine.

Development of SARS-CoV-2 variant protein microarray for profiling humoral immunity in vaccinated subjects.

SARS-CoV-2 is quickly evolving from wild-type to many variants and spreading around the globe. Since many people have been vaccinated with various types of vaccines, it is crucial to develop a high throughput platform for measuring the antibody responses and surrogate neutralizing activities against multiple SARS-CoV-2 variants. To meet this need, the present study developed a SARS-CoV-2 variant (CoVariant) array which consists of the extracellular domain of spike variants, e.g., wild-type, D614G, B.1.1.7, B.1.351, P.1, B.1.617, B.1.617.1, B.1.617.2, and B.1.617.3. A surrogate virus neutralization on the CoVariant array was established to quantify the bindings of antibody and host receptor ACE2 simultaneously to spike variants. By using a chimeric anti-spike antibody, we demonstrated a broad binding spectrum of antibodies while inhibiting the bindings of ACE2 to spike variants. To monitor the humoral immunities after vaccination, we collected serums from unvaccinated, partial, or fully vaccinated individuals with either mRNA-1273 or AZD1222 (ChAdOx1). The results showed partial vaccination increased the surrogate neutralization against all the mutants while full vaccination boosted the most. Although IgG, IgA, and IgM isotypes correlated with surrogate neutralizing activities, they behave differently throughout the vaccination processes. Overall, this study developed CoVariant arrays and assays for profiling the humoral responses which are useful for immune assessment, vaccine research, and drug development.

Sickle Cell Disease (SCD) As a Risk for COVI19 Compared to Those without SCD Among Patients Admitted in a Large Urban Center, As Estimated By PCR Sars-v-2 Positive Vs Negative Testing

A diagnosis of SCD is considered to be at risk for COVD19. To further define the association between SCD and infection with COVID-19, we estimated risk, by comparing presence or absence of COVID19 infections in individuals with and without SCD admitted concurrently to a large urban health care facility (Grady Memorial Hospital, Atlanta, GA;960 beds, 5th largest public hospital in the US). Primary outcome was a positive or negative COVID-19 diagnosis as defined bySARS-CoV-2 PCR testing. A patient was considered to be COVID-19 positive if tested positive withSARS-CoV-2 PCR for the first time, anytime during the study period, irrespective of number of tests. A patient was considered to be COVID-19 negative if patient had no positive tests during the study period, and had one or moreSARS-CoV-2 PCR negative tests. For COVID19 positive patients, the admission of theSARS-CoV-2 PCR positive test was included in the analysis. For COVID19 negative patients, the first admission with aSARS-CoV-2 PCR negative test was considered for analysis. For this interim analysis, SCD was defined by ICD10 and registry data. Clinical diagnosis such as obesity and respiratory failure were defined by ICD10 coding. Data was obtained from quarterly centralized Epic EMR data extractions. Analysis of outcome of COVID19 positive vs negatives was stratified in four separate analysis: all admissions, ICU admissions, those with respiratory failure and those who died. Multivariate dichotomous logistic regression analyses modeled binary outcome effect of SCD, adjusted for age (<40 vs. > 40 years), sex at birth (females vs. males) and obesity (SAS version 9.4 was used for statistical analyses and overall significance level was set at 0.05). To ensure population homogeneity analysis was conducted on patient ages 20 to 60 years that were Black/African American and admitted from the Emergency Department for a short stay and/or the medicine service (variable interactions at a p<0.01). The study was approved by the institutional review board and by the hospital research oversight committee. Overall, between 3/23/2020 and 6/30/2020, 23697 patients were admitted once or more to Grady Memorial Hospital with one or more PCR sars-cov-2 test, of these 405 were patients with SCD (1.7%). Of the total, 2566 patients (10.8%) tested positive for COVID-19, and 48 patients with SCD (11.8%) were positive. Of 7041 (29.7%) were part of the study population, 332 (4.7%) where patients with SCD (hemoglobin [hb] SS/Sbeta0 =252, hbSC n=55, hbS beta thalassemia+ or hbS beta thalassemia undetermined n=21). Among patients without SCD, 36.3% were female, (n=2557) and among patients with SCD, 53.6% (n=178). The mean age of patients without SCD was: 51.1 years (standard deviation [std]) +/- 19.5 years), and for those with SCD: 35.0 years (std +/- 12.0 years). Results of univariate and multivariate analysis are presented in the table. In conclusion, in a Black/African American patients admitted from the Emergency Room for observation and/or the internal medicine service, when adjusted for age, gender and obesity, with SCD are at a significant increased risk for admissions with COVID-19 infection in general as well as ICU admission or admission with respiratory failures. Further studies can help articulate the risk associated with SCD as well as its potential interaction with other factors, with attention to confounders. [Formula presented] Disclosures: No relevant conflicts of interest to declare.

An mRNA vaccine to prevent genital herpes.

The rapid development of two nucleoside-modified mRNA vaccines that are safe and highly effective against coronavirus disease 2019 has transformed the vaccine field. The mRNA technology has the advantage of accelerated immunogen discovery, induction of robust immune responses, and rapid scale up of manufacturing. Efforts to develop genital herpes vaccines have been ongoing for 8 decades without success. The advent of mRNA technology has the potential to change that narrative. Developing a genital herpes vaccine is a high public health priority. A prophylactic genital herpes vaccine should prevent HSV-1 and HSV-2 genital lesions and infection of dorsal root ganglia, the site of latency. Vaccine immunity should be durable for decades, perhaps with the assistance of booster doses. While these goals have been elusive, new efforts with nucleoside-modified mRNA-lipid nanoparticle vaccines show great promise. We review past approaches to vaccine development that were unsuccessful or partially successful in large phase 3 trials, and describe lessons learned from these trials. We discuss our trivalent mRNA-lipid nanoparticle approach for a prophylactic genital herpes vaccine and the ability of the vaccine to induce higher titers of neutralizing antibodies and more durable CD4+ T follicular helper cell and memory B cell responses than protein-adjuvanted vaccines.

Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models.

Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA- compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.

Walkthrough digital virtual hospice tour: A survey study to explore practicality and acceptability for patients

Background: Patients referred to a hospice may feel trepidation about this unknown environment, and the word hospice can carry stigma for some. Virtual Reality (VR) applications allow users to feel present and become immersed in a realistic computer-generated environment and are used for instance by estate agents for house viewings. Our cancer hospital in Cardiff uses 360° photo/video technology on tablet computers to give patients a 'digital tour' of two regional hospices. Aims: To evaluate whether the use of these 360° walkthrough tours of local hospices is acceptable to patients/proxy and readily implementable within a clinical environment. Methods: 360° filming/photography was undertaken in two local hospices & uploaded to hospital media pads. An online survey was created to assess patients'/relatives' experience. Patients on the ward for whom a hospice referral was suggested by the MDT were offered this digital tour and were included in this survey. Staff were asked whether it was easy to use. Results: Of 25 patients/relatives, 90% felt the 360° tour improved their readiness for hospice transfer. Also, 95% of patients/relatives stated they would recommend it to other patients being referred to hospices. All patients/proxy found it acceptable. Staff felt the 360° tour was easily integrated into their work, and preferred using tablet computers over VR headsets. Conclusion: The technological use of 360° hospice photographic views as an introduction to the hospice infrastructure can make a difference to patients/proxy and addresses the fear of an unknown environment. Integration of this innovative technology into the clinical environment is feasible and appears acceptable to patients. Creating 360° imagery in local hospices was not technologically difficult, but is aided by availability of staff interested in digital media. Furthermore, informal hospice visits were curtailed during the Covid-19 pandemic, driving up the usage of these virtual tours significantly.

Development and Application of Human Coronavirus Protein Microarray for Specificity Analysis.

Coronavirus is an enveloped RNA virus that causes mild to severe respiratory diseases in humans, including HKU1-CoV, 229E-CoV, NL63-CoV, OC43-CoV, SARS-CoV, MERS-CoV, and SARS-CoV-2. Due to the outbreak of SARS-CoV-2, it is important to identify the patients and investigate their immune responses. Protein microarray is one of the best platforms to profile the antibodies in the blood because of its fast, multiplexed, and sensitive nature. To fully understand the immune responses and biological specificities, this study developed a human coronavirus (HCoV) protein microarray and included all seven human coronaviruses and three influenza viruses. Each protein was printed in triplicate and formed 14 identical blocks per array. The HCoV protein microarray showed high reproducibility and sensitivity to the monoclonal antibodies against spike and nucleocapsid protein with detection limits of 10-200 pg. The HCoV proteins that were immobilized on the array were properly folded and functional by showing interactions with a known human receptor, e.g., ACE2. By profiling the serum IgG and IgA from 32 COVID-19 patients and 36 healthy patients, the HCoV protein microarray demonstrated 97% sensitivity and 97% specificity with two biomarkers. The results also showed the cross-reactivity of IgG and IgA in COVID-19 patients to spike proteins from various coronaviruses, including that from SARS-CoV, HKU1-CoV, and OC43-CoV. Finally, an innate immune protein named surfactant protein D showed broad affinities to spike proteins in all human coronaviruses. Overall, the HCoV protein microarray is multiplexed, sensitive, and specific, which is useful in diagnosis, immune assessment, biological development, and drug screening.