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1.
Rural Remote Health ; 22(4): 7657, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2081330

ABSTRACT

INTRODUCTION: The first outbreak of the omicron variant of COVID-19 in the Torres and Cape region of Far North Queensland in Australia was declared in late December 2021. A COVID-19 Care at Home program was created to support the health and non-health needs of people with COVID-19 and their families throughout the mandatory isolation periods and included centralising the coordination and delivery of COVID-19 therapeutics. The therapeutics available included one intravenous monoclonal antibody (sotrovimab) and two oral antiviral therapies: nirmatrelvir and ritonavir (Paxlovid®) and molnupiravir (Lagevrio®). This article describes the uptake and delivery of this therapeutics program. METHODS: COVID-19 cases were documented in a notification database, screened to determine eligibility for COVID-19 therapies and prioritised based on case age, vaccination status, immunosuppression status and existing comorbidities, in line with Queensland clinical guidelines. Eligible cases were individually contacted by phone to discuss treatment options, and administration of therapies were coordinated in partnership with local primary healthcare centres and hospitals. RESULTS: A total of 4744 cases were notified during the outbreak period, of which 217 (4.6%) were deemed eligible for treatment after medical review. Treatment was offered to 148/217 cases (68.2%), with 90/148 cases (60.8%) declining treatment and 53/148 cases (35.8%) receiving therapeutic treatment for COVID-19. Among these 53 cases, 29 received sotrovimab (54.7%), 20 received Paxlovid (37.7%) and four received Lagevrio (7.5%). First Nations people accounted for 48/53 cases (90.6%) who received treatment, and COVID-19 therapeutics were delivered to cases in 16 remote First Nations communities during the outbreak period. CONCLUSION: The COVID-19 Care at Home program demonstrated a novel, public health led approach to delivering time-critical medications to individuals across a large, remote and logistically complex region. The application of similar models to outbreaks and chronic conditions of public health importance offers potential to address many health access inequities experienced by remote Australian First Nations communities.


Subject(s)
COVID-19 , Health Services, Indigenous , Humans , Native Hawaiian or Other Pacific Islander , Queensland/epidemiology , Australia/epidemiology , COVID-19/epidemiology , Ritonavir , SARS-CoV-2 , Disease Outbreaks , Antibodies, Monoclonal , Antiviral Agents
2.
Int J Ment Health Nurs ; 31(6): 1467-1479, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1992826

ABSTRACT

A strong association exists between the quality of nurse-service user therapeutic relationship and care outcomes on acute mental health inpatient wards. Despite evidence that service users desire improved therapeutic engagement, and registered mental health nurses recognize the benefits of therapeutic relationships, such interactions remain sub-optimal. There is a dearth of evidence on factors influencing implementation of interventions to support and encourage therapeutic engagement. This study aimed to understand the barriers and enablers to implementation of the Therapeutic Engagement Questionnaire (TEQ), across fifteen acute inpatient wards in seven English mental health organizations. Qualitative methods were used in which data were collected from ethnographic field notes and documentary review, coded, and analysed using thematic analysis. Theoretical framing supported data analysis and interpretation. Reporting adheres to the Standards for Reporting Qualitative Research. The TEQ as an evidence-based intervention co-produced with service users and nurses was valued and welcomed by many nurse directors, senior clinicians, and ward managers. However, a range of practical and perceptual factors impeded implementation. Furthermore, many existing contextual challenges for intervention implementation in acute inpatient wards were magnified by the COVID-19 pandemic. Suitable facilitation to address these barriers can help support implementation of the TEQ, with some transferability to implementation of other interventions in these settings. Our study suggests several facilitation methods, brought together in a conceptual model, including encouragement of reflective, facilitative discussion meetings among stakeholders and researchers, effort put into winning nurse 'buy-in' and identifying and supporting ward-level agents of change.


Subject(s)
COVID-19 , Mental Health , Humans , Inpatients/psychology , Pandemics , Qualitative Research , Surveys and Questionnaires
3.
Oxf Open Immunol ; 2(1): iqaa007, 2021.
Article in English | MEDLINE | ID: covidwho-1081925

ABSTRACT

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.

4.
mBio ; 11(3)2020 06 23.
Article in English | MEDLINE | ID: covidwho-612678

ABSTRACT

It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 "don't eat me" signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents.IMPORTANCE Immune responses to infectious agents are initiated when a pathogen or its components bind to pattern recognition receptors (PRRs). PRR binding sets off a cascade of events that activates immune responses. We now show that, in addition to activating immune responses, PRR signaling also initiates an immunosuppressive response, probably to limit inflammation. The importance of the current findings is that blockade of immunomodulatory signaling, which is mediated by the upregulation of the CD47 molecule, can lead to enhanced immune responses to any pathogen that triggers PRR signaling. Since most or all pathogens trigger PRRs, CD47 blockade could be used to speed up and strengthen both innate and adaptive immune responses when medically indicated. Such immunotherapy could be done without a requirement for knowing the HLA type of the individual, the specific antigens of the pathogen, or, in the case of bacterial infections, the antimicrobial resistance profile.


Subject(s)
Betacoronavirus/immunology , CD47 Antigen/metabolism , Immunomodulation/immunology , Receptors, Pattern Recognition/immunology , A549 Cells , Adaptive Immunity/immunology , Animals , CD47 Antigen/genetics , Cell Line, Tumor , Cytokines/immunology , Female , Humans , Immunity, Innate/immunology , Lymphocytic choriomeningitis virus/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mycobacterium tuberculosis/immunology , SARS-CoV-2 , Up-Regulation/immunology
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