The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses.

The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. Unlike cellular membranes, procoagulant amino-PLs were present on the external side of the viral envelope at levels exceeding those on activated platelets. Accordingly, virions directly promoted blood coagulation. To investigate whether these differences could enable selective targeting of the viral envelope in vivo, we tested whether oral rinses containing lipid-disrupting chemicals could reduce infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, povidone-iodine, or chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-s oral rinse with cetylpyridinium chloride mouthwash eliminated live virus in the oral cavity of patients with coronavirus disease 19 for at least 1 h, whereas povidone-iodine and saline mouthwashes were ineffective. We conclude that the SARS-CoV-2 lipid envelope i) is distinct from the host plasma membrane, which may enable design of selective antiviral approaches; ii) contains exposed phosphatidylethanolamine and phosphatidylserine, which may influence thrombosis, pathogenicity, and inflammation; and iii) can be selectively targeted in vivo by specific oral rinses.

Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study.

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.

Standards for research in NHS Wales critical care units: A modified Delphi study.

Introduction: The importance of research and development in all aspects of healthcare is well acknowledged. Within critical care, national guidelines provide a limited number of standards and series of recommendations on Research and Development (R&D) activity. The aim of this study was to create a broader set of standards in support of R&D activity in critical care departments. Methods: A modified Delphi study was undertaken across NHS Wales critical care units. Proposed standards were developed by a group of experts, which across three rounds, majority agreement was sought. Additional standards were added based on participant's responses. Results: This study identified 49 standards for R&D activity within critical care units in NHS Wales. All these standards reached majority agreement, as determined by >70% of multi-disciplinary participants determine each standard as essential. Conclusions: The results of this study will be utilised within Wales to inform wider service specification with regard workforce requirements, responsibilities, reporting and collaboration.

Nurse and allied health professional experiences and attitudes toward critical care research: A national questionnaire study.

Introduction: The aim of this study was to investigate nurse and allied health professional experiences and attitudes toward critical care research in Wales. Methods: Data were collected related to demographic characteristics, involvement in and understanding of research, perceived influences and attitudes towards research. We calculated means (ranges) for continuous variable and frequencies (proportions) for discrete variables and performed an exploratory factor analysis. Results: Response rate was 55% (n = 575). Most respondents (84%) had participated in research less than five times in the previous 12 months, yet 91% believed research led to improved care patients. Only 32% respondents felt they were encouraged by managers to participate in research. Only 25% respondents had undertaken research training. Few respondents (29%) reported receiving adequate information regarding study progress or results (25%). Linear regression models indicate that a higher level of formal education was associated with a more positive view of research across all attitude factors. Promotion of research by colleagues and recognition/ opportunities for involvement in critical care research, were positively associated with the acceptability and experience of research. Discussion: A number of factors have been identified that could be targeted to improve recruitment to critical care research, including identification of staff to promote research, improved communication of study progress and findings and management encouragement to attend research training. Staff attitudes were positive towards the benefit of research on patient care in Wales.

Prevalence and Outcomes of Acute Hypoxaemic Respiratory Failure in Wales: The PANDORA-WALES Study.

BACKGROUND: We aimed to identify the prevalence of acute hypoxaemic respiratory failure (AHRF) in the intensive care unit (ICU) and its associated mortality. The secondary aim was to describe ventilatory management as well as the use of rescue therapies. METHODS: Multi-centre prospective study in nine hospitals in Wales, UK, over 2-month periods. All patients admitted to an ICU were screened for AHRF and followed-up until discharge from the ICU. Data were collected from patient charts on patient demographics, clinical characteristics, management and outcomes. RESULTS: Out of 2215 critical care admissions, 886 patients received mechanical ventilation. A total of 197 patients met inclusion criteria and were recruited. Seventy (35.5%) were non-survivors. Non-survivors were significantly older, had higher SOFA scores and received more vasopressor support than survivors. Twenty-five (12.7%) patients who fulfilled the Berlin definition of acute respiratory distress syndrome (ARDS) during the ICU stay without impact on overall survival. Rescue therapies were rarely used. Analysis of ventilation showed that median Vt was 7.1 mL/kg PBW (IQR 5.9-9.1) and 21.3% of patients had optimal ventilation during their ICU stay. CONCLUSIONS: One in four mechanically ventilated patients have AHRF. Despite advances of care and better, but not optimal, utilisation of low tidal volume ventilation, mortality remains high.

A multicentre prospective evaluation of alcohol-related admissions to intensive care units in Wales.

PURPOSE: We conducted a prospective multicentre study in 13 Welsh intensive care units to assess what proportion of intensive care admissions relate to alcohol, and how outcomes among these patients compare with non-alcohol related admissions. MATERIALS AND METHODS: Data were prospectively collected for one month between June and July 2015. Every intensive care admission was screened for alcohol associations based on ICD-10 criteria, using a pre-designed pro-forma. Follow-up data were collected at 60 days using a pre-existing database (WardWatcher; Critical Care Audit Ltd, England). Outcomes included: lengths of mechanical ventilation, intensive care units and hospital stay; intensive care units and hospital mortality. RESULTS: Alcohol contributed directly to 10% of all ICU admissions and to 11% of unplanned admissions. These patients were younger (52 vs. 66, p = 0.0011), more likely to be male (68% vs. 52%, p = 0.014) and had more prolonged ventilation (p = 0.019) There was no significant difference between the groups with respect to length of stay or mortality. CONCLUSIONS: Alcohol contributes to a significant proportion of ICU admissions in Wales, a Western European country with a relatively low number of ICU beds per capita. Strategies to address this impact should be explored.