Optimizing mRNA vaccines and virusmediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification

With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.

Medicines management of long-term conditions during the COVID19 pandemic: a narrative systematic review

Introduction: Due to lockdown measures associated with the COVID 19 pandemic (1), there were substantial changes to healthcare delivery, including the suspension of face-to-face medical appointments, expansion of telehealth and changes to medication protocols.(2) It is important to learn from the successes and challenges of this period to ensure we adapt and improve how we support people to take medicines in the future. Aim(s): We sought to conduct a systematic review to explore the different approaches used to deliver medicines management services for people living with long term conditions (LTCs) during the pandemic and identify strategies that could be integrated into standard care. Method(s): We conducted a systematic review across 3 large databases: MEDLINE (OVID), EMBASE (OVID) and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Our research question and search strategy was developed using the PICO framework (Population: adults with LTCs, Intervention: medicines management during the COVID 19 pandemic;no comparison group. Outcome(s): any aspect relating to medicines management. Search terms relating to 'long term conditions', 'medication management' and 'COVID-19' were used. One reviewer (LM) screened all titles, s, and full texts. We included studies discussing medication management of LTCs, in patients of all ages and healthcare settings, throughout the pandemic. Primary literature sources, feasibility studies and case studies, were included. We excluded studies solely focusing on disease monitoring, or the treatment of COVID/ 'long Covid'. One reviewer performed a thematic analysis, synthesising the findings into themes and sub-themes, which were discussed with a further reviewer (CT). A critical appraisal was performed using the Critical Appraisal Skills Programme checklists. Result(s): The search returned 2365 results. After deduplication, articles were removed at the title (n=1070) (n=813) and full text (n=232) stages. 31 studies were included. Studies were conducted in India (n=6), US (n=5), international (n=4), France (n=2), Italy (n=2), and one each from China, Japan, Jordan, Mexico, Morocco, Nigeria, Romania, Saudi Arabia, Spain, UK, UK and US, and location not specified. Most studies (n=17) employed subjective methods of data collection (surveys/ questionnaires). We identified 6 themes. These were: changes in consultation type, for instance using teleconsultations and smartphone apps to monitor glucose control and diabetic management. Studies described temporary changes to treatment protocols e.g., using oral chemotherapy to reduce the need for in-person appointments and reduce the infection risk associated with intravenous administration. Control of certain conditions for example epilepsy was reduced in some studies. Patients missed doses due to drug shortages associated with disruptions in the medication supply chain, particularly in low-income countries. Finally, we identified prescribing trend changes in certain classes of medicines (e.g. reduced biologic usage due to immunosuppression risk) and an increase in patients self-medicating conditions including anxiety and depression, with associated safety risks. Conclusion(s): This review suggested that certain medical conditions such as diabetes and hypertension were more suited to remote monitoring with technological interventions such as smartphone apps. While other conditions e.g., cancer and epilepsy, demonstrated a greater need for in-person care. Countries of lower socioeconomic status were disproportionately affected by the pandemic.

Semi-Supervised Machine Learning for Analyzing COVID-19 Related Twitter Data for Asian Hate Speech

The COVID-19 pandemic left a lot of people sick, tired, and frustrated. Many people expressed their feelings on social media through comments and posts. Detecting hate speech on social media is important to help reduce the spread of racist comments. Machine learning algorithms can be used to classify hate speech. In our experiments, we implement semi-supervised machine learning algorithms to classify Twitter data. We used a count vectorizer as the feature and a support vector machine (SVM) classifier to classify COVID-19 related Twitter data while changing the amount of labeled data available. We found that self-training semi-supervised machine learning has similar effectiveness to supervised learning when there is significantly less training data available. © 2022 IEEE.

The "problem” of teacher quality: exploring challenges and opportunities in developing teacher quality during the Covid-19 global pandemic in England

Teachers and teacher education are often presented as "problems” to be solved, with policy solutions that focus on ways to make teachers "better” and improve teacher "quality” by introducing prescriptive strategies. We investigate the ways Covid-19-related changes to university and school-based facets of Initial Teacher Education (ITE) in England influence teacher quality in relation to both student teachers and early career teachers, working in secondary schools. Drawing on 34 interviews with school leaders, school mentors and ITE tutors, we critically explore the ways in which teacher quality was developed through key aspects of teachers' pedagogy and practice during the pandemic crisis when schools were closed and teaching moved online. Our findings show that the pandemic crisis has highlighted the different facets of teacher quality which arguably disrupt narrow and prescriptive understandings of what constitutes "quality” in policy terms. Although there were many instances of challenge in the development of new and student teachers, our data also shows how ITE tutors, school mentors and leaders responded creatively to the crisis. Participants highlighted the opportunities afforded by the pandemic to develop diverse and innovative pedagogies and practice, enhance students' subject knowledge, as well as overcome some of the challenges in other areas of pedagogy and practice. Furthermore, the study shows that teacher quality was not substantially reduced despite the challenges arising from the pandemic and concerns that pre-service teachers would not be ready and prepared for a career in the classroom. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

'Safe spaces and places': the value of design-led methodologies in developing online narratives

This paper considers the value of a design-led methodological approach, adopted during the COVID-19 pandemic to facilitate online interviews with young people (aged 15-17) who had been involved in crime and violence in Newcastle-upon-Tyne, UK. The development of an original digital workshop and set of exercises (referred to as a tool) using interactive methods engaged criminalised youths online and gathered qualitative data regarding their experiences of crime and violence. The research demonstrated how principles of design can be used to empower participants, overcome communication barriers, obtain rich data through online methods, and move away from a traditional 'interview' experience, creating a safer space for more genuine accounts and narratives. Thus, this paper suggests that researchers of youth crime and violence, and social scientists more broadly, may wish to consider how adopting design-led methodologies can allow places and spaces for participants' narratives to develop.

Adverse reactions associated with the transfusion of blood components processed with different methods: The impact of automated pre-storage leukocyte depletion

Background: In modern transfusion therapy, whole blood is used only in certain limited circumstances and trust is placed in the use of specific blood components (BCs). BC must be processed using appropriate validated procedures, including measures to avoid contamination and microbial growth in the initial and final prepared BCs (Directive 2005/62/EC, Annex 6.42). Consequently, methods of centrifugation of whole blood, filtration of leukocytes, washing and irradiation must be specified. Aim(s): We analyse national data on non-haemolytic pyrexial and allergic reactions related to blood transfusion reported to the Coordinating Haemovigilance Centre and Surveillance of Transfusion (SKAEM) of the Hellenic National Public Health Organization (EODY) by hospital Transfusion Departments in 2010-2020, in relation to the processing procedures applied using conventional blood bank methodologies. The results of an automated blood processing system employed in two hospital blood banks are also discussed in view of the national policy for stepwise implementation of a centralized automated processing procedure aiming to improve the quality and safety of blood transfusion. Method/Study: Annual haemovigilance data for all adverse reactions associated with BCs transfusion are reported to SKAEM using standardized questionnaires. Protocols are in line with International Haemovigilance Network guidelines and ISBT definitions of the types of adverse reactions associated with blood transfusion. The processing procedures used are: buffy coat removal, leukocyte depletion after storage, pre-storage leukodepletion, red cell washing in additive solution, and irradiation. The Reveos Automated Blood System (Terumo BCT) was also used, processing 4 units of whole blood to two components (plasma and red cells) or three main components (plasma, concentrated red cells and interim platelet unit) according to the manufacturer's instructions. Both protocols collect a Leukopak unit containing the main leukocyte fraction which is discarded. The resulting RCC is further leukoreduced by gravity using the Reveos in-line filter. Consistent leukoreduction of plasma is done through the simultaneous centrifugation/ extraction step of this method. Result(s): 13005 adverse reactions (AR) associated with the transfusion of 7 894 054 blood components were reported. Febrile nonhaemolytic transfusion reactions were 43.7% and allergic 37%. The distribution of febrile reactions in relation to processing procedure was: in RBCs with buffy coat 61.7%, without buffy coat 10.9%, leukodepletion after storage 16.5%, leukodepletion pre-storage 6.7%, washing 4.1% and irradiation 0.1%. Results from the use of the Reveos Automated Processing System (Terumo BCT) by the National Blood Centre for processing the blood collected and used by two large HBBs over a two-year period showed a statistically significant reduction of pyrexial reactions (p = 0.044 in one hospital and 0.002 in the other) in comparison with the relevant data before the use of this system. The corresponding difference in the allergic reactions was not statistically significant. Conclusion(s): This study demonstrates high incidence of pyrexial nonhaemolytic and allergic reactions associated with the use of blood components processed without leukodepletion, particularly during the COVID-19 pandemic when blood transfusion services were shortstaffed owing to re-assignment to other duties. Compliance with Good Practice Guidelines and improvement of blood processing and safety by automation should be a national priority.

Managing Medications During a Pandemic: A Mixed-Methods Study of Perception of Adult Kidney Transplant Recipients and Those Waiting for a Kidney Transplant

Purpose: Patients interact with healthcare providers (HCP) and pharmacists to manage medications. Little is known about the impact of COVID-19 on medication management. The purpose of this study was to describe medication management, HCP/pharmacist interactions, and adherence, including initiation, implementation and persistence, during the COVID-19 pandemic in kidney transplant (KT) patients and those on the KT wait list. Method(s): The IRB determined this study was exempt. Using a mixed methods design, 340 adults at a transplant center in the midwestern US were recruited. The Managing Medications in the Midst of a Pandemic Survey measured HCP/pharmacy encounters and medication management. The Basel assessment of adherence to medications scale measured medication adherence. Result(s): The sample average age was 58.2 years, 61% male, and 86% White. During the COVID-19 pandemic, 90% had/were currently practicing socially distancing, 87% had /were currently wearing a face mask when out in public, 19% had/were currently diagnosed with COVID-19, and 84% received the vaccine. Additional survey results include: Medication management: 82% percent plan/organize their own medications. Healthcare team interactions: 98% talked with their HCP since the beginning of social distancing;13% delayed seeing a HCP because of COVID-19 concerns. Pharmacy interactions: 11% changed their method of obtaining medications from pharmacy due to social distancing and 3.5% delayed refilling medications. Medication adherence-Initiation: 2.5% were prescribed a new medication but did not begin taking it. Medication adherence-Implementation: in the 4 weeks prior to the survey, 19% missed a dose, 6.7% skipped a dose, 16% took a medication more than 2-hour time difference from the prescribed time, and 2.5% altered prescribed amount. Medication adherence- Persistence: 3.4% stopped taking a prescribed medication without a doctor's order during the pandemic. Conclusion(s): A majority of the patients waiting for a KT and KT patients acted to prevent COVID-19 but some still contracted the virus. The pandemic changed medication management interactions with HCP and pharmacists. Adherence implementation problems were nearly 20%. Findings are relevant to transplant HCP and pharmacists, who must support patients attempting to manage and adhere to prescribed medications during the pandemic.

Perceptions and attitudes of blood donors in Greece towards vaccination against COVID-19

Background: The speed of development of COVID-19 vaccines, and the need to balance their effectiveness versus possible complications, raised doubts over vaccine acceptance in the first period of the national vaccination campaign aiming at herd immunity against SARSCoV- 2. In the field of transfusion medicine, timely vaccination of the blood donor population represents a powerful measure in the general strategy to sustain blood collection and optimize the blood supply. Aims: To explore perceptions and attitudes of blood donors towards SARS-CoV-2 vaccination, in comparison to the general population. Methods: Donors in 20 blood collection services throughout Greece in May-October 2021 answered voluntarily and confidentially a structured questionnaire, covering: donor demographics;date and type of blood donation;frequency of donation;history of COVID-19;SARSCoV- 2 vaccination including type and doses;reasons for getting vaccinated or not;satisfaction with the vaccination procedure;side effects;feelings after vaccination;certainty about return to normality;and recommending vaccination to others. Hesitancy and beliefs leading to not getting vaccinated, worries over future side effects, and not recommending vaccination to others were also investigated. Results: Completed questionnaires were received from 3361 blood donors (61% response rate) aged 18-65 years during blood sessions at mobile sites and within hospitals. Respondents were mainly males (72%). A very high proportion (92%) of responders had completed high school of higher education and the majority resided in large cities. Almost half were regular donors. A small proportion (5.4%) had undergone a mild COVID19 infection and 17.3% mentioned COVID-19 in a relative. 52% had already been vaccinated. The proportion vaccinated increased steadily throughout the study. Vaccine acceptance was highest in males 45-54 years old and in females 18-24 and 50-59 years old. All four EMA approved vaccines (Pfizer, Moderna, Astra Zeneca and Johnson) were used. Mild complications were reported by 21% of vaccinated donors after the first dose and 19% after the second. Thirty-five donors reported fever and local pain at the vaccination site after both doses. The vast majority (79%) of vaccinated donors were very satisfied with the vaccination procedure and only 10 complained. After vaccination, 20% of donors felt safe and protected against COVID-19 and 55% intended to continue all recommended personal protective measures in their families and felt satisfaction for doing the right thing. Among unvaccinated respondents, 48% were awaiting their appointment, 19% were undecided, 16% were afraid of complications, a few said that they were waiting for more information about the beneficial effect of the vaccines, or that COVID-19 is not a severe disease, and 10% did not specify their reasons. In the general population of Greece surveyed in May 2021 in the Flash Eurobarometer study, COVID-19 vaccination acceptance was 59%. The proportion of those with negative perception and attitude towards vaccination was 12%. Key reasons for getting vaccinated or not were similar to those found in blood donors. Summary/Conclusions: The benefits of vaccination and the need to continue all personal protection measures were highly recognized by blood donors, whether already vaccinated or awaiting vaccination. The perceptions and attitudes towards vaccination against COVID-19, especially of regular donors, are compatible with their high social, altruistic and humanitarian behaviour.

Outbreak of SARS-CoV-2 in a teenage discotheque in Northern Ireland-November 2021.

OBJECTIVES: To report key findings associated with an outbreak of SARS-CoV-2 following a teenage disco in Northern Ireland. STUDY DESIGN: Observational case series. METHODS: A case was defined as an individual who attended the event with a positive SARS-CoV-2 result between 6th and 20th November 2021. Demographic and clinical information, including symptom status, date of onset and school attended, were recorded during contact tracing. Vaccination status was derived from the COVID-19 Vaccine Management System. Forty-five samples associated with the outbreak were sequenced as part of the NI Whole Genome Sequencing (WGS) programme. RESULTS: Only 2.4% (5/205) of cases received a COVID-19 vaccine more than 14 days before the event. 84.9% (174/205) had received no vaccine at the time of the event and 12.7% (26/205) had been vaccinated within 14 days, offering only limited disease protection. The AY4.2.2 lineage of two cases who attended the event after symptom onset was found in 69% of sequenced outbreak cases. CONCLUSIONS: This study demonstrates extensive COVID-19 transmission in largely unvaccinated teenagers in an indoor venue with limited social distancing, close social contact and mixing, limited ventilation and singing and shouting. Public Health authorities developing COVID-19 entertainment regulations should consider congregations of teenagers in these settings, especially if vaccination rates are low in this group or they are not eligible for vaccination at that time. Public communications should be developed to ensure young people with COVID-19 symptoms follow public guidance regarding self-isolation and in particular avoid indoor events with larger numbers.

Covid-19 vaccine dissemination: A public health ethical evaluation of Pennsylvania's plan during Phase 1A.

Background: The novel COVID-19 pandemic afforded public health leaders an opportunity to expedite vaccine development and dissemination. The United States found itself faced with the arduous task of ensuring swift and equitable distribution of limited resources, in the midst of often-competing priorities, including public health ethics, medical ethics, economic demands, and societal strains. Methodology: Using the American Public Health Association's (APHA) newly revised public health code of ethics, which provides a decision-making framework and guidance for ethical analysis, we analyzed how Pennsylvania's COVID-19 vaccine dissemination plan aligned with the four core functions of public health ethics inquiry. Results/Discussion: Upon investigation, the state's plan evidenced use of public health ethics in goal setting and design. However, the core public health value given the highest priority, promoting health and safety, competed with the other core public health values of inclusivity and engagement, health justice and equity, and professionalism and trust. Despite known social disparities and risk factors, the state plan for COVID-19 vaccine dissemination aligned closely with federal guidance and prioritized all healthcare personnel and long-term care facility populations over high-risk individuals residing in the community. Conclusion/Perspectives: Should another pandemic necessitate allocation of scarce resources, especially preventative measures such as vaccines, decision-making agencies must consider disparate populations in planning and dissemination of material to the public. Any anticipated limitations in the ability to fulfill public health ethical principles should be clearly communicated to the public prior to implementation, thereby increasing trust.

[Association of COVID-19 dissemination with symptoms of anxiety and depression among university students]

BACKGROUND: Evidence about the impact of the COVID-19 pandemic on the mental health of specific subpopulations- such as university students-is needed as communities prepare for future waves. AIMS: To study the association of proximity of COVID-19 with symptoms of anxiety and depression in university students. METHODS: This trend study analyzed weekly cross-sectional surveys of probabilistic samples of students from the University of British Columbia for 13 weeks through the first wave of COVID-19. The main variable assessed was propinquity of COVID-19, defined as "knowing someone who tested positive for COVID-19", which was specified at different levels: knowing someone anywhere globally, in Canada, in Vancouver, in their course, or at home. Proximity was included in multivariable linear regressions to assess its association with primary outcomes, including 30-day symptoms of anxiety and/or depression. RESULTS: Of 1,388 respondents (adjusted response rate=50%), 5.6% knew someone with COVID-19 in Vancouver, 0.8% in their course, and 0.3% at home. Ten percent were overwhelmed and unable to access help. Knowing someone in Vancouver was associated with an 11 percentage-point increase in the probability of 30-day anxiety symptoms (SE=0,05;p<=0,05), moderated by gender, with a significant interaction of the exposure and being female (coefficient= 20(SE=0,09), p<=0,05). No association was found with depressive symptoms. CONCLUSION: Propinquity of COVID-19 cases may increase the likelihood of anxiety symptoms in students, particularly amongst men. Most students report coping well, but additional supports are needed for an emotionally overwhelmed minority who report being unable to access help.

National population prevalence of antibodies to SARS-CoV-2 among pregnant women in Scotland during the second wave of the COVID-19 pandemic: a prospective national serosurvey.

OBJECTIVES: This study aimed to determine SARS-CoV-2 seroprevalence among pregnant women in the Scottish population during the second wave of the COVID-19 pandemic. STUDY DESIGN: Prospective national serosurvey. METHODS: We tested 13,428 residual samples retrieved from pregnant women participating in the first trimester combined ultrasound and biochemical screening for fetal trisomy across Scotland for SARS-CoV-2 antibodies over a 6-month period from November 2020 to April 2021. Seroprevalence estimates were adjusted for the sensitivity and specificity of the assays and weighted to reference populations. RESULTS: Seroprevalence rates in the antenatal samples significantly increased from 5.5% (95% confidence interval [CI] 4.7%-6.5%) in the 5-week period up to and including International Organization for Standardization (ISO) Week 51 (w/b Monday 14 December 2020) to 11.3% (95% CI 10.1%-12.6%) in the 5-week period up to and including ISO Week 14 (w/b Monday 5 April 2021). Increasing seroprevalence trends across the second wave were observed among all age groups. CONCLUSIONS: By the end of the second wave of the COVID-19 pandemic, approximately one in 10 women tested around the end of the first trimester of pregnancy had antibodies to SARS-CoV-2, suggesting that the vast majority were still susceptible to COVID-19 as they progressed to the later stages of pregnancy, when risks from infection are elevated for both mother and baby.

The hidden dangers of staying home: a London trauma unit experience of lockdown during the COVID-19 virus pandemic.

INTRODUCTION: The COVID-19 pandemic resulted in reconfiguration of the NHS. Elective services were stopped and trauma services focused on decreasing patient-clinician interactions and managing injuries nonoperatively wherever possible. The everyday life of the general public changed dramatically with the introduction of a national lockdown to prevent the spread of COVID-19. This paper looks at the experience of a South West London trauma unit. MATERIALS AND METHODS: All patients reviewed in fracture clinic and by the orthopaedic on-call team between 23 March to 23 April 2020 were included. Data on the mechanism of injury and whether this was a usual activity, the injury sustained and its management were collected. RESULTS: A total of 167 trauma injuries were seen, compared with 735 new patients with injuries in the previous month. The number of trauma operations completed decreased by 38%; 55% of injuries occurred inside the home and 44% outside the home during daily exercise. Some 31% of injuries were secondary to a new activity taken up during lockdown. Three open fractures and two polytrauma cases were seen that would have normally been managed at the local major trauma centre. CONCLUSION: Overall, both the number of injuries seen and trauma operations completed during the enforced lockdown decreased. This is probably due to a change in the way the general public are living their lives, and the reconfigurations within the NHS in response to the COVID-19 pandemic. This is an interesting time within trauma and orthopaedic departments, as they continue to adapt to the changing injuries and working environment.

Initiating home spirometry for children during the COVID-19 pandemic - A practical guide.

The COVID-19 pandemic has led to a rapid escalation in use of home monitoring and video consultations in children with a variety of chronic respiratory conditions. Our department set up a home spirometry service from scratch once it became evident that we needed to keep patients away from hospital clinics whenever possible. We faced a number of challenges but now have around 400 children using home spirometers. There are a number of portable spirometers available, some with online platforms. The technology, particularly the software/apps interface, has been improved by the companies in response to issues that have arisen. We believe the use of home monitoring is here to stay.

Post-donation information and haemovigilance reporting for COVID-19 in Greece: Information supporting the absence of SARS-CoV-2 possible transmission through blood components.

BACKGROUND: Although the SARS-CoV-2 virus is transmitted mainly through the respiratory tract, possible transmission by transfusion from asymptomatic carriers should be explored. As yet there are no reports of transfusion transmission of COVID-19. Haemovigilance findings within a three-month surveillance period during the new coronavirus pandemic are presented. MATERIALS AND METHODS: Due to great demand and shortage, blood sessions in outpatient facilities were organized during the high prevalence period of COVID-19, alongside a national plan to monitor the evolving public health situation by random molecular screening of high-risk groups of the population. Haemovigilance protocols were implemented as well as surveillance for any COVID-19 case reported post-transfusion. A 14-day quarantine and follow-up molecular and antibody testing of any COVID-19 positive case was obligatory. RESULTS: Post-donation, post-transfusion information and molecular testing of swab samples collected from three asymptomatic donors at risk for COVID-19, revealed the case of an immunosupressed patient who had been transfused with whole blood derived platelets from a donor subsequently diagnosed with COVID-19. The recipient exhibited no symptoms of the disease. Molecular and antibody testing results were negative. CONCLUSION: Haemovigilance provided information supporting the absence of transfusion transmission of COVID-19, thus strengthening the hypothesis that, even if it cannot yet be definitively ruled out, COVID-19 is not transmitted through blood transfusion. As of early June 2020, a perfect test does not exist, therefore haemovigilance along with the implementation of strict proactive measures is crucial to identify eluding asymptomatic individuals and ensure blood safety during the pandemic.