Effect of Immunosuppression on the Immune Response to SARS-CoV-2 Infection and Vaccination.

Immunosuppressive treatment in patients with rheumatic diseases can maintain disease remission but also increase risk of infection. Their response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is frequently blunted. In this study we evaluated the effect of immunosuppression exposure on humoral and T cell immune responses to SARS-CoV-2 infection and vaccination in two distinct cohorts of patients; one during acute SARS-CoV-2 infection and 3 months later during convalescence, and another prior to SARS-CoV-2 vaccination, with follow up sampling 6 weeks after vaccination. Results were compared between rituximab-exposed (in previous 6 months), immunosuppression-exposed (in previous 3 months), and non-immunosuppressed groups. The immune cell phenotype was defined by flow cytometry and ELISA. Antigen specific T cell responses were estimated using a whole blood stimulation interferon-γ release assay. A focused post-vaccine assessment of rituximab-treated patients using high dimensional spectral cytometry was conducted. Acute SARS-CoV-2 infection was characterised by T cell lymphopenia, and a reduction in NK cells and naïve CD4 and CD8 cells, without any significant differences between immunosuppressed and non-immunosuppressed patient groups. Conversely, activated CD4 and CD8 cell counts increased in non-immunosuppressed patients with acute SARS-CoV-2 infection but this response was blunted in the presence of immunosuppression. In rituximab-treated patients, antigen-specific T cell responses were preserved in SARS-CoV-2 vaccination, but patients were unable to mount an appropriate humoral response.

Efficacy of facemasks in preventing transmission of COVID-19 in non-healthcare settings: A scoping review.

Background: During the COVID-19 pandemic, an abundance of literature relating to the efficacy of face masks on reducing transmission of COVID-19 in non-healthcare settings emerged. Aim/objective: The aim of this scoping review was to allow the identification of: types of evidence conducted in this area; knowledge gaps and common concepts relating to mask efficacy in non-healthcare settings. Methods: A comprehensive literature search was conducted in PubMed, CINAHL, MEDLINE, Embase and the Irish Management Institute bibliographic database on December 15th, 2021. All types of face masks were included. Of 722 records, 16 were included after full text screening. Findings/results: Themes from an adapted model of Howard et al. framework were used to group results and identify common concepts. The grouped thematic results were then applied to the socio-ecological model. This illustrated the multifactorial elements determining the efficacy of masks themselves while also illustrating how other factors such as individual behaviours, social interactions, settings and national policy can influence the degree of the protective effect. Discussion: The findings from this scoping review indicate that an abundance of experimental literature is available indicating that masks are effective at preventing COVID-19 transmission but their degree of efficacy is impacted by external factors. This review highlights that the quality of the evidence available is low.

Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction.

BACKGROUND: Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance. Additionally, we postulate that ongoing immune cell dysfunction may be linked to sustained EC and coagulation activation. PATIENTS AND METHODS: Fifty patients were reviewed at a minimum of 6 weeks following acute COVID-19. ADAMTS-13, Weibel Palade Body (WPB) proteins, and angiogenesis-related proteins were assessed and clinical evaluation and immunophenotyping performed. Comparisons were made with healthy controls (n = 20) and acute COVID-19 patients (n = 36). RESULTS: ADAMTS-13 levels were reduced (p = 0.009) and the VWF-ADAMTS-13 ratio was increased in convalescence (p = 0.0004). Levels of platelet factor 4 (PF4), a putative protector of VWF, were also elevated (p = 0.0001). A non-significant increase in WPB proteins Angiopoietin-2 (Ang-2) and Osteoprotegerin (OPG) was observed in convalescent patients and WPB markers correlated with EC parameters. Enhanced expression of 21 angiogenesis-related proteins was observed in convalescent COVID-19. Finally, immunophenotyping revealed significantly elevated intermediate monocytes and activated CD4+ and CD8+ T cells in convalescence, which correlated with thrombin generation and endotheliopathy markers, respectively. CONCLUSION: Our data provide insights into sustained EC activation, dysregulated angiogenesis, and VWF/ADAMTS-13 axis imbalance in convalescent COVID-19. In keeping with the pivotal role of immunothrombosis in acute COVID-19, our findings support the hypothesis that abnormal T cell and monocyte populations may be important in the context of persistent EC activation and hemostatic dysfunction during convalescence.

Severe COVID-19 is characterised by inflammation and immature myeloid cells early in disease progression.

SARS-CoV-2 infection causes a wide spectrum of disease severity. Identifying the immunological characteristics of severe disease and the risk factors for their development are important in the management of COVID-19. This study aimed to identify and rank clinical and immunological features associated with progression to severe COVID-19 in order to investigate an immunological signature of severe disease. One hundred and eight patients with positive SARS-CoV-2 PCR were recruited. Routine clinical and laboratory markers were measured, as well as myeloid and lymphoid whole-blood immunophenotyping and measurement of the pro-inflammatory cytokines IL-6 and soluble CD25. All analysis was carried out in a routine hospital diagnostic laboratory. Univariate analysis demonstrated that severe disease was most strongly associated with elevated CRP and IL-6, loss of DLA-DR expression on monocytes and CD10 expression on neutrophils. Unbiased machine learning demonstrated that these four features were strongly associated with severe disease, with an average prediction score for severe disease of 0.925. These results demonstrate that these four markers could be used to identify patients developing severe COVID-19 and allow timely delivery of therapeutics.

Democratizing epilepsy care: Utility and usability of an electronic patient portal.

OBJECTIVES: Electronic patient portals (ePortals) can facilitate greater healthcare democratization by providing patients and/or their authorized care partners with secure access to their medical records when and where needed. Such democratization can promote effective healthcare provider-patient partnerships, shared decision-making, and greater patient engagement in managing their health condition. This study examined the usefulness of providing individualized services and care in epilepsy (PiSCES), an epilepsy ePortal, as an enabler of more democratized epilepsy care. METHODS: Seventy-two individuals with epilepsy and 18 care partners were invited to report on their experience of interacting via PiSCES with clinical documents (epilepsy care summary record; epilepsy clinic letters) authored about them by healthcare providers. The OpenNotes reporting tool was adapted to capture participant experience. RESULTS: Twenty-five percent of invited patients and 44% of invited care partners reported on interacting with their epilepsy care summary; 14% of patients and 67% of care partners invited reported on their epilepsy clinic letters. Participant testimonials illustrate the value of PiSCES in: promoting autonomy, aiding memory, developing the knowledgeable patient, and enhancing healthcare partnerships. Ninety-six percent and 100% of respondents, respectively, reported understanding their epilepsy care summary and epilepsy clinic letter; 77% said the summary described their epilepsy history to date; 96% indicated that the letter provided an accurate description of their clinical encounter; 92% and 96%, respectively, valued access to their summary record and clinic letters; 77% of summary record and 73% clinic letter respondents reported learning something about their epilepsy or the healthcare service via PiSCES. Illustrating their potential patient and care partner safety role, 42% respondents identified inaccuracies in their clinical documents which were subsequently resolved by a clinician. SIGNIFICANCE: In the post-digital world highly customized on-demand products and services have come to be expected. Similarly, in epilepsy care, technologies such as PiSCES can enable more personalized, transparent, and engaging services.

Longitudinal Analysis of COVID-19 Patients Shows Age-Associated T Cell Changes Independent of Ongoing Ill-Health.

Objectives: The immunological and inflammatory changes following acute COVID-19 are hugely variable. Persistent clinical symptoms following resolution of initial infection, termed long COVID, are also hugely variable, but association with immunological changes has not been described. We investigate changing immunological parameters in convalescent COVID-19 and interrogate their potential relationships with persistent symptoms. Methods: We performed paired immunophenotyping at initial SARS-CoV-2 infection and convalescence (n=40, median 68 days) and validated findings in 71 further patients at median 101 days convalescence. Results were compared to 40 pre-pandemic controls. Fatigue and exercise tolerance were assessed as cardinal features of long COVID using the Chalder Fatigue Scale and 6-minute-walk test. The relationships between these clinical outcomes and convalescent immunological results were investigated. Results: We identify persistent expansion of intermediate monocytes, effector CD8+, activated CD4+ and CD8+ T cells, and reduced naïve CD4+ and CD8+ T cells at 68 days, with activated CD8+ T cells remaining increased at 101 days. Patients >60 years also demonstrate reduced naïve CD4+ and CD8+ T cells and expanded activated CD4+ T cells at 101 days. Ill-health, fatigue, and reduced exercise tolerance were common in this cohort. These symptoms were not associated with immune cell populations or circulating inflammatory cytokines. Conclusion: We demonstrate myeloid recovery but persistent T cell abnormalities in convalescent COVID-19 patients more than three months after initial infection. These changes are more marked with age and are independent of ongoing subjective ill-health, fatigue and reduced exercise tolerance.

Coproducing health and well-being in partnership with patients, families, and healthcare providers: A qualitative study exploring the role of an epilepsy patient portal.

BACKGROUND: Coproduced epilepsy care sees people with epilepsy (PwE), their care-proxies, and healthcare providers (HCPs), working together as partners to build strong relationships, improve communication, trust, and share decision-making. Coproduction underpins good quality patient- and family-centered care (PFCC) that is responsive to individual patient needs, preferences, and values. By facilitating information sharing and exchange between partners, electronic patient portals (ePortal) can enable coproduction. This paper explores what HCPs, PwE, and their care-proxies value from their user experience of PiSCES, the Irish epilepsy ePortal. METHODS: A purposeful sample of actors involved in the receipt and delivery of epilepsy care and services were recruited via adult epilepsy centers at St James's and Beaumont Hospitals in Dublin. Interactive codesign sessions, surveys, and focus groups were used to elicit perspectives from PwE, care-proxies, and HCPs to understand their perception of how PiSCES could enhance or inhibit the epilepsy care process. RESULTS: Results illustrate that participants welcome the role PiSCES can play in: empowering PwE/care-proxies, strengthening confidence in the healthcare system; aiding memory; advancing health literacy, motivating PwE to understand their condition better; acting as a passport of care between different clinical settings; and creating a foundation for stronger coproduction partnerships. PiSCES was generally embraced; however, some HCPs expressed plausible concerns about how clinical implementation might impact their work practices. CONCLUSION: "Nothing about me without me" is a core value of the PiSCES initiative, recognizing that people need to be included in the planning of their own treatment and care. Our data show that PwE, their care-proxies, and HCPs value PiSCES potential, particularly in bolstering healthcare partnerships that foster inclusion, confidence, and trust.

Igniting intersectoral collaboration in chronic disease management: a participatory action research study on epilepsy care in Ireland.

Models of care developed to improve the lives of people with chronic diseases highlight integrated care as essential to meeting their needs and achieving person (patient)-centered care (PCC). Nevertheless, barriers to collaborative practice and siloed work environments persist. To set in motion some groundwork for intersectoral collaboration this study brought two expert groups of epilepsy care practitioners together to engage in participatory action research (PAR). The expert practitioner groups were hospital-based epilepsy specialist nurses (ESNs) and community-based resource officers (CROs). The PAR highlighted, that while the participants share a mutual interest in caring for people with epilepsy, underdeveloped CRO-ESN relationships, arising from unconscious bias and ambiguity can result in missed opportunities for optimal care coordination with consequent potential for unnecessary replication and waste of finite resources. However, through dialogue and critical self-reflection, a growing emotional connection between the disciplines evolved over the course of the PAR. This allowed for buds of collaboration to develop with CROs and ESNs working together to tackle some of the key barriers to their collaboration.

Are patients ready for integrated person-centered care? A qualitative study of people with epilepsy in Ireland.

The National Clinical Programme for Epilepsy (NCPE) in Ireland aims to deliver a holistic model of integrated person-centered care (PCC) that addresses the full spectrum of biomedical and psychosocial needs of people with epilepsy (PwE). However, like all strategic plans, the model encompasses an inherent set of assumptions about the readiness of the environment to implement and sustain the actions required to realize its goals. In this study, through the lens of PwE, the Irish epilepsy care setting was explored to understand its capacity to adopt a new paradigm of integrated PCC. Focus groups and semi-structured one-to-one interviews were employed to capture the qualitative experiences of a sample of Irish PwE (n = 27) in the context of the care that they receive. Participants were from different regions of the country and were aged between 18 and 55 years with 1 to 42 years since diagnosis (YSD). Highlighting a gap between policy intent and action on the ground, findings suggest that patient readiness to adopt a new model of care cannot be assumed. Expectations, preferences, behaviors, and values of PwE may sustain the more traditional constructions of healthcare delivery rather than the integrated PCC goals of reform. These culturally constituted perceptions illustrate that PwE do not instinctively appreciate the goals of healthcare reform nor the different behavior expected from them within a reformed healthcare system. Recalibrating deep-rooted patient views is necessary to accomplish the aspirations of integrated PCC. Patient engagement emphasizing the meaningful role that they can play in shaping their healthcare services is vital.

The rhetoric and reality of integrated patient-centered care for healthcare providers: An ethnographic exploration of epilepsy care in Ireland.

In line with healthcare reform across the world, the National Clinical Programme for Epilepsy (NCPE) in Ireland describes a model that aims to achieve holistic integrated person (patient)-centered care (PCC). While generally welcomed by stakeholders, the steps required to realize the NCPE ambition and the preparedness of those involved to make the journey are not clear. This study explored the perceptions of healthcare providers in the Irish epilepsy care ecosystem to understand their level of readiness to realize the benefits of an integrated PCC model. Ethnographic fieldwork including observations of different clinical settings across three regions in Ireland and one-to-one interviews with consultant epileptologists (n = 3), epilepsy specialist nurses (n = 5), general practitioners (n = 4), and senior healthcare managers (n = 3) were conducted. While there is a person-centered ambiance and a disposition toward advancing integrated PCC, there are limits to the readiness of the epilepsy care environment to fully meet the aspirations of healthcare reform. These are the following: underdeveloped healthcare partnerships;, poor care coordination;, unintended consequences of innovation;, and tension between pace and productivity. In the journey from policy to practice, the following multiple tensions collide: policy aims to improve services for all patients while simultaneously individualizing care; demands for productivity limit the time and space required to engage in incremental and iterative improvement initiatives. Understanding these tensions is an essential first step on the pathway to integrated PCC implementation.