Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α.

OBJECTIVES: Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-ß and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown. METHODS: We retrospectively analysed a monocentric longitudinal cohort of 609 patients with SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed by abolishment of Madin-Darby bovine kidney cell protection by IFN-α2 against vesicular stomatitis virus challenge. Serum-neutralising activity against IFN-α2, IFN-ß and IFN-ω was also determined with a reporter luciferase activity assay. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns. RESULTS: Neutralising and non-neutralising anti-IFN-α antibodies are present at a frequency of 3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-α, unlike non-neutralising AAbs, are associated with reduced IFN-α serum levels and a reduced likelihood to develop active disease. However, they predispose patients to an increased risk of herpes zoster and severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE is mostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-α AAbs do not interfere with COVID-19 vaccine humoral immunogenicity. CONCLUSION: The production of non-neutralising and neutralising anti-IFN-I antibodies in SLE is likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficial effect on disease activity, yet a greater viral risk. This finding reinforces the recommendations for vaccination against SARS-CoV-2 in SLE.

Changes in Health-Related Behaviours and Mental Health in a UK Public Sample during the First Set of COVID-19 Public Health Restrictions.

Public health restrictions, in response to the COVID-19 pandemic, have had potentially wide-ranging, unintended effects on health-related behaviours such as diet and physical activity and also affected mental health due to reduced social interactions. This study explored how health-related behaviours and mental health were impacted in a sample of the UK public during the first set of COVID-19 public health restrictions. Two online surveys were administered in the UK, one within the first three months of the restrictions (Timepoints 1 (T1-involving pre-pandemic recall) and 2/T2) and another ten weeks later (Timepoint 3/T3). Moderate-vigorous physical activity (MVPA), outdoor time, sitting time, screen time and sexual activity were self-reported. Diet was assessed using the Dietary Instrument for Nutrition Education questionnaire. Mental health was measured using the short-form Warwick-Edinburgh Mental Wellbeing Scale and Becks' Anxiety and Depression Inventories. Differences between timepoints were explored using the Friedman, Wilcoxon signed-rank, McNemar and McNemar-Bowker tests. Two hundred and ninety-six adults (74% under 65 years old; 65% female) provided data across all timepoints. Between T1 and T2, MVPA, time outdoors and sexual activity decreased while sitting, and screen time increased (p < 0.05). Between T2 and T3, saturated fat intake, MVPA, time outdoors, and mental wellbeing increased while sitting, screen time and anxiety symptoms decreased (p < 0.05). This study found that depending on the level of COVID-19 public health restrictions in place, there appeared to be a varying impact on different health-related behaviours and mental health. As countries emerge from restrictions, it is prudent to direct necessary resources to address these important public health issues.

Changes in Health-Related Behaviours and Mental Health in a UK Public Sample during the First Set of COVID-19 Public Health Restrictions

Public health restrictions, in response to the COVID-19 pandemic, have had potentially wide-ranging, unintended effects on health-related behaviours such as diet and physical activity and also affected mental health due to reduced social interactions. This study explored how health-related behaviours and mental health were impacted in a sample of the UK public during the first set of COVID-19 public health restrictions. Two online surveys were administered in the UK, one within the first three months of the restrictions (Timepoints 1 (T1-involving pre-pandemic recall) and 2/T2) and another ten weeks later (Timepoint 3/T3). Moderate–vigorous physical activity (MVPA), outdoor time, sitting time, screen time and sexual activity were self-reported. Diet was assessed using the Dietary Instrument for Nutrition Education questionnaire. Mental health was measured using the short-form Warwick–Edinburgh Mental Wellbeing Scale and Becks' Anxiety and Depression Inventories. Differences between timepoints were explored using the Friedman, Wilcoxon signed-rank, McNemar and McNemar–Bowker tests. Two hundred and ninety-six adults (74% under 65 years old;65% female) provided data across all timepoints. Between T1 and T2, MVPA, time outdoors and sexual activity decreased while sitting, and screen time increased (p < 0.05). Between T2 and T3, saturated fat intake, MVPA, time outdoors, and mental wellbeing increased while sitting, screen time and anxiety symptoms decreased (p < 0.05). This study found that depending on the level of COVID-19 public health restrictions in place, there appeared to be a varying impact on different health-related behaviours and mental health. As countries emerge from restrictions, it is prudent to direct necessary resources to address these important public health issues.

Ensuring the quality and quantity of personal protective equipment (PPE) by enhancing the procurement process in Northern Ireland during the coronavirus disease 2019 pandemic: Challenges in the procurement process for PPE in NI.

This article outlines the purchasing process for personal protective equipment that was established for Health and Social Care in Northern Ireland in response to the outbreak of coronavirus disease 2019. The Business Services Organisation Procurement and Logistics Service, who are the sole provider of goods and services for Health and Social Care organisations, was faced with an unprecedented demand for personal protective equipment in response to the coronavirus disease 2019 pandemic. The usual procurement process was further complicated by changing messages within guidelines which resulted in confusion and anxiety when determining whether or not a product would meet the required safety guidance and was therefore suitable for purchase. In order to address these issues in a rapidly changing and escalating scenario the Department of Health asked the Business Services Organisation Procurement and Logistics Service to work with the Medicines Optimisation Innovation Centre to maximise the availability of personal protective equipment whilst ensuring that it met all requisite quality and standards. A process was implemented whereby the Medicines Optimisation Innovation Centre validated all pertinent essential documentation relating to products to ensure that all applicable standards were met, with the Business Services Organisation Procurement and Logistics Service completing all procurement due diligence tasks in line with both normal and coronavirus disease 2019 emergency derogations. It is evident from the data presented that whilst there were a significant number of potential options for supply, a large proportion of these were rejected due to failure to meet the quality assurance criteria. Thus, by the process that was put in place, a large number of unsuitable products were not purchased and only those that met extant standards were approved.

Joining the workforce during the COVID-19 pandemic: views of Allied Health Profession students.

In the United Kingdom, the onset of the COVID-19 pandemic placed great pressures on universities to ensure final year health care students completed their studies earlier than planned in order to join the National Health Service workforce. This study aimed to explore the anticipations and support needs of final year allied health profession students transitioning to practice during a pandemic. Final year university students across seven healthcare professions were asked to complete an online survey. Demographic data were analyzed by descriptive statistics and responses to open questions were explored using content analysis. Sixty participants completed the survey. Content analysis regarding students' anticipations, fears, and support needs identified the following themes: professional identity and growth; opportunities for improvement; preparedness for transition from university to the workplace, the workplace environment; COVID-19; support from lecturers; daily support within the workplace and innovative methods of support. Although the transition from student to practitioner continues to be a stressful period, only a minority of participants reported COVID-19 as an explicit stressor. However, as the effects of COVID-19 continue to evolve in the United Kingdom, universities and healthcare trusts must ensure adequate supports are in place for recent graduates navigating this transition during a healthcare crisis.

The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.

BACKGROUND: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. METHODS: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. RESULTS: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1ß, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-ß), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. CONCLUSION: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.

Correlates of symptoms of anxiety and depression and mental wellbeing associated with COVID-19: a cross-sectional study of UK-based respondents.

BACKGROUND: The aim was to assess the impact of COVID-19 self-isolation/social distancing on mental health, and potential correlates, among a sample of the UK population. METHODS: A cross-sectional study. Mental health was measured using the Beck Anxiety and Depression Inventory. Mental wellbeing was measured using The Short Warwick-Edinburgh Mental Well-being Scale. Data collected on predictors included sex, age, marital status, employment, annual income, region, current smoking, current alcohol consumption, physical multimorbidity, any physical symptoms experienced during self-isolation/social distancing, and the number of days of self-isolation/social distancing. The association between potential predictors and poor mental health was studied using a multivariable logistic regression. RESULTS: 932 participants were included. Factors associated with poor mental health were sex (reference: male; female: OR=1.89, 95%CI=1.34-2.68), age (18-24 years: reference;45-54 years: OR=0.27, 95%CI=0.14-0.53; 55-64 years: OR=0.24, 95%CI=0.12-0.47; 65-74years: OR=0.10, 95% CI=0.05-0.22; and ≥75years: OR=0.08,95% CI=0.03-0.24),annual income (<£15,000: reference; £25,000-<£40,000: OR=0.54, 95% CI=0.31-0.93; £40,000-<£60,000: OR=0.39, 95% CI=0.22-0.69; and ≥£60,000: OR=0.38, 95% CI=0.21-0.67), current smoking (yes: OR=2.59, 95%CI=1.62-4.20), and physical multimorbidity (OR=2.35, 95%CI=1.61-3.46). CONCLUSIONS: In this sample of UK adults self-isolating/social distancing females, younger age groups, those with a lower annual income, current smokers and those with physical multimorbidity were associated with higher levels of poor mental health.