Characteristics of pediatric patients with multiple sclerosis and related disorders infected with SARS-CoV-2.

BACKGROUND: Pediatric patients with multiple sclerosis (POMS) and related disorders, clinically isolated syndrome (CIS), myelin oligodendrocyte glycoprotein antibody disorder (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), are commonly treated with immunosuppressants. Understanding the impact of SARS-CoV-2 infection in patients may inform treatment decisions. OBJECTIVE: Characterize SARS-CoV-2 infection prevalence and severity among a cohort of patients with POMS and related disorders, as well as the impact of disease-modifying therapies (DMTs). METHODS: POMS and related disorders patients enrolled in a large, prospective registry were screened for COVID-19 during standard-of-care neurology visits. If confirmed positive of having infection, further analysis was undertaken. RESULTS: Six hundred and sixty-nine patients were surveyed between March 2020 and August 2021. There were 73 confirmed COVID-19 infections. Eight of nine hospitalized patients (89%), and all patients admitted to the ICU were treated with B cell depleting therapy. The unadjusted odds ratio of hospitalization among those who tested positive of having had COVID-19 was 15.27 among those on B-cell-depleting therapy (p = 0.016). CONCLUSIONS: B-cell-depleting treatment was associated with a higher risk of COVID-19, higher rates of hospitalization, and ICU admission, suggesting this therapy carries a higher risk of severe infection in POMS and related disorders.

Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19.

IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signal via different modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates pro-inflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL-6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making.

Prehospital Testing and Surveillance for SARS-CoV-2: A Special Report from the Sacramento (California USA) Mobile Integrated Health Unit.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has killed nearly 800,000 Americans since early 2020. The disease has disproportionately affected older Americans, men, persons of color, and those living in congregate living facilities. Sacramento County (California USA) has used a novel Mobile Integrated Health Unit (MIH) to test hundreds of patients who dwell in congregate living facilities, including skilled nursing facilities (SNF), residential care facilities (ie, assisted living facilities [ALF] and board and care facilities [BCF]), and inpatient psychiatric facilities (PSY), for SARS-CoV-2. METHODS: The MIH was authorized and rapidly created at the beginning of the COVID-19 pandemic as a joint venture between the Sacramento County Department of Public Health (SCDPH) and several fire-based Emergency Medical Services (EMS) agencies within the county to perform SARS-CoV-2 testing and surveillance in a prehospital setting at a number of congregate living facilities. All adult patients (≥18 years) who were tested for SARS-CoV-2 infection by the MIH from March 31, 2020 through April 30, 2020 and lived in congregate living facilities were included in this retrospective descriptive cohort. Demographic and laboratory data were collected to describe the cohort of patients tested by the MIH. RESULTS: During the study period, the MIH tested a total of 323 patients from 15 facilities in Sacramento County. The median age of patients tested was 66 years and the majority were female (72%). Overall, 72 patients (22%) tested positive for SARS-CoV-2 in congregate living settings, a higher rate of positivity than was measured across the county during the same time period. CONCLUSION: The MIH was a novel method of epidemic surveillance that succeeded in delivering effective and efficient testing to patients who reside in congregate living facilities and was able to accurately identify pockets of infection within otherwise low prevalence areas. Cooperative prehospital models are an effective model to deliver out-of-hospital testing and disease surveillance that may serve as a blueprint for community-based care delivery for a number of disease states and future epidemics or pandemics.

Interleukin-6: obstacles to targeting a complex cytokine in critical illness.

Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and anti-inflammatory functions. An adequate understanding of the complex processes by which IL-6 signalling occurs is crucial for the correct interpretation of IL-6 concentrations in the blood or lung, the use of IL-6 as a critical care biomarker, or the design of effective anti-IL-6 strategies. Here, we outline the role of IL-6 in health and disease, explain the different types of IL-6 signalling and their contribution to the net biological effect of the cytokine, describe the approaches to IL-6 inhibition that are currently available, and discuss implications for the future use of treatments such as tocilizumab in the critical care setting.

The Experiences of Carers of Adults With Intellectual Disabilities During the First COVID-19 Lockdown Period.

Background: The recent COVID-19 pandemic led to widespread international restrictions, severely impacting on health and social care services. For many individuals with an intellectual disability (ID) this meant reduced access to services and support for them and their carers. Aim: The aim of this study was to gain insight into the ways parents of adults with ID coped during the first 2020 lockdown period. Methods: Eight parents of adults with ID were interviewed. The recordings of these interviews were subjected to a thematic analysis. Results: Four main themes were identified: powerless and unappreciated; coping under lockdown; support; and the impact of lockdown on well-being. Conclusions: The parents of adults with ID who made up our sample reported that they received little support from services and experienced a sense of powerlessness. Nevertheless, they were open to accepting support from family and friends and showed remarkable resilience. These findings are discussed in the light of the Willner et al. (2020) survey results on parental mental health and coping, and suggestions for future service provision during pandemic conditions are proposed.

The experiences of mothers of children and young people with intellectual disabilities during the first COVID-19 lockdown period.

BACKGROUND: Recent COVID-19 lockdown restrictions resulted in reduced access to educational, professional and social support systems for children with intellectual disabilities and their carers. AIM: The aim of this study was to gain insight into the ways mothers of children with intellectual disabilities coped during the first 2020 lockdown period. METHODS: Eight mothers of children with intellectual disabilities were interviewed. The recordings of these interviews were subjected to a thematic analysis. RESULTS: Three main themes were identified: carrying the burden; a time of stress; and embracing change and looking to the future. CONCLUSIONS: All mothers experienced increased burden and stress. However, some also described some positive impact of lockdown conditions on them as well as on their child's well-being and behaviour. These findings are discussed in the light of the (Journal of Applied Research in Intellectual Disabilities, 33, 2020, 1523) survey results on parental coping and suggestions for future service provision during pandemic conditions are proposed.

Preferences for a COVID-19 vaccine in Australia.

In absence of a COVID-19 vaccine, testing, contact tracing and social restrictions are among the most powerful strategies adopted around the world to slow down the spread of the pandemic. Citizens of most countries are suffering major physical, psychological and economic distress. At this stage, a safe and effective COVID-19 vaccine is the most sustainable option to manage the current pandemic. However, vaccine hesitancy by even a small subset of the population can undermine the success of this strategy. The objective of this research is to investigate the vaccine characteristics that matter the most to Australian citizens and to explore the potential uptake of a COVID-19 vaccine in Australia. Through a stated preference experiment, preferences towards a COVID-19 vaccine of 2136 residents of the Australian states and territories were collected and analysed via a latent class model. Results show that preferences for mild adverse cases, mode of administration, location of administration, price and effectiveness are heterogeneous. Conversely, preferences for immediacy and severe reactions are homogeneous, with respondents preferring a shorter period until vaccine is available and lower instances of severe side effects. The expected uptake of the vaccine is estimated under three different scenarios, with the value of 86% obtained for an average scenario. By calculating individual preferences, the willingness to pay is estimated for immediacy, effectiveness, mild and severe side effects.

Interleukin-6 signalling in health and disease.

Biochemically, interleukin-6 belongs to the class of four-helical cytokines. The cytokine can be synthesised and secreted by many cells. It acts via a cell surface-expressed interleukin-6 receptor, which is not signalling competent. This receptor, when complexed with interleukin-6, associates with the signalling receptor glycoprotein 130 kDa (gp130), which becomes dimerised and initiates intracellular signalling via the Janus kinase/signal transducer and activator of transcription and rat sarcoma proto oncogene/mitogen-activated protein kinase/phosphoinositide-3 kinase pathways. Physiologically, interleukin-6 is involved in the regulation of haematopoiesis and the coordination of the innate and acquired immune systems. Additionally, interleukin-6 plays an important role in the regulation of metabolism, in neural development and survival, and in the development and maintenance of various cancers. Although interleukin-6 is mostly regarded as a pro-inflammatory cytokine, there are numerous examples of protective and regenerative functions of this cytokine. This review will explain the molecular mechanisms of the, in part opposing, activities of the cytokine interleukin-6.

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge.

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.

Effect of the COVID-19 pandemic on the mental health of carers of people with intellectual disabilities.

INTRODUCTION: The measures implemented to manage the COVID-19 pandemic have been shown to impair mental health. This problem is likely to be exacerbated for carers. METHOD: Informal carers (mainly parents) of children and adults with intellectual disabilities, and a comparison group of parents of children without disabilities, completed an online questionnaire. Almost all the data were collected while strict lockdown conditions were in place. RESULTS: Relative to carers of children without intellectual disability, carers of both children and adults with intellectual disability had significantly greater levels of a wish fulfilment coping style, defeat/entrapment, anxiety, and depression. Differences were 2-3 times greater than reported in earlier pre-pandemic studies. Positive correlations were found between objective stress scores and all mental health outcomes. Despite their greater mental health needs, carers of those with intellectual disability received less social support from a variety of sources. CONCLUSIONS: The greater mental health needs of carers in the context of lesser social support raises serious concerns. We consider the policy implications of these findings.