We remember: a critical care COVID-19 remembrance service

BackgroundThere is increasing recognition that palliative care when provided appropriately to critically ill patients with life limiting illness can not only offer physical, psychosocial and spiritual care to patients but also helps improve family and staff satisfaction.1 Given this, a multi-disciplinary group within the critical care unit of the Royal Alexandra Hospital was established to improve the delivery of palliative care. A staff survey highlighted the desire from staff to improve bereavement support for both families and staff. In light of this, the decision was made to host a remembrance service in memory of patients who had passed away in the unit during Covid-19 pandemic.MethodsFunding was secured from the charity To Absent Friends. The critical care database, Ward Watcher, was utilised to collate the details of patients who had passed away in the unit from March 2020 until August 2021. The number of patients identified was 237. The families of each patient were invited. A non-denominational remembrance service consisting of readings, live music and acts of remembrance was held in November 2022.Data13 staff and 40 families attended. 69% of staff who attended completed a feedback survey. 89% reported that the service brought them benefit and 100% reported that they would want the service to be held again. Written feedback from families included: ‘The Service on Saturday became our ‘closure' time and helped me get a new perspective on the last two years'ConclusionsAlthough the feedback received was limited, the data suggests that a remembrance service can be of benefit to both families and staff, particularly in the context of a pandemic when visiting was curtailed. This collaborative project has also demonstrated the need for further cross specialty working in order to ensure the delivery of palliative care within a critical care unit.ReferenceIto K, George N, Wilson J, et al. Primary palliative care recommendations for critical care clinicians. J Intensive Care 2022;10:20. https://doi.org/10.1186/s40560-022-00612-9

The impacts of the COVID-19 shock on sustainability and farmer livelihoods in Sri Lanka.

The COVID-19 pandemic and its handling in Sri Lanka has affected vegetable farmers in numerous ways and these impacts will constrain the country's move towards sustainable development. A field level study with vegetable farmers and key informants was carried out using exploratory research to understand, describe and analyze the impact of COVID-19 on the livelihoods of vegetable farmers and its relevance in achieving SDG 1. Data were supplemented by an extensive literature review. The analysis showed that the pandemic's impact on vegetable farmers in Sri Lanka is multidimensional and will increase vulnerability among vegetable farmers, for the long run. Adapting alternative inputs and marketing strategies, provision of immediate financial support, promoting innovative technology and service provision, and implementing intervention strategies tailored to farmer heterogeneity will improve farmer livelihoods and the prosperity of the sector.

Risk Factors for Severe Outcomes in Patients With Systemic Vasculitis and COVID-19: A Binational, Registry-Based Cohort Study.

OBJECTIVE: COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID-19. We undertook this study to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS: A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. RESULTS: The cohort included 65 patients with systemic vasculitis who developed COVID-19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1-14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9-38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. CONCLUSION: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision-making relating to the risk of severe COVID-19 in this vulnerable patient group.

Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies.

Of the 16 non-structural proteins (Nsps) encoded by SARS CoV-2, Nsp3 is the largest and plays important roles in the viral life cycle. Being a large, multidomain, transmembrane protein, Nsp3 has been the most challenging Nsp to characterize. Encoded within Nsp3 is the papain-like protease domain (PLpro) that cleaves not only the viral polypeptide but also K48-linked polyubiquitin and the ubiquitin-like modifier, ISG15, from host cell proteins. We here compare the interactors of PLpro and Nsp3 and find a largely overlapping interactome. Intriguingly, we find that near full length Nsp3 is a more active protease compared to the minimal catalytic domain of PLpro. Using a MALDI-TOF based assay, we screen 1971 approved clinical compounds and identify five compounds that inhibit PLpro with IC50s in the low micromolar range but showed cross reactivity with other human deubiquitinases and had no significant antiviral activity in cellular SARS-CoV-2 infection assays. We therefore looked for alternative methods to block PLpro activity and engineered competitive nanobodies that bind to PLpro at the substrate binding site with nanomolar affinity thus inhibiting the enzyme. Our work highlights the importance of studying Nsp3 and provides tools and valuable insights to investigate Nsp3 biology during the viral infection cycle.

A literature review of the economics of COVID-19.

The goal of this piece is to survey the developing and rapidly growing literature on the economic consequences of COVID-19 and the governmental responses, and to synthetize the insights emerging from a very large number of studies. This survey: (i) provides an overview of the data sets and the techniques employed to measure social distancing and COVID-19 cases and deaths; (ii) reviews the literature on the determinants of compliance with and the effectiveness of social distancing; (iii) mentions the macroeconomic and financial impacts including the modelling of plausible mechanisms; (iv) summarizes the literature on the socioeconomic consequences of COVID-19, focusing on those aspects related to labor, health, gender, discrimination, and the environment; and (v) summarizes the literature on public policy responses.

Development of a High-Throughput Screening Assay to Identify Inhibitors of the SARS-CoV-2 Guanine-N7-Methyltransferase Using RapidFire Mass Spectrometry.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents a significant threat to human health. Despite its similarity to related coronaviruses, there are currently no specific treatments for COVID-19 infection, and therefore there is an urgent need to develop therapies for this and future coronavirus outbreaks. Formation of the cap at the 5' end of viral RNA has been shown to help coronaviruses evade host defenses. Nonstructural protein 14 (nsp14) is responsible for N7-methylation of the cap guanosine in coronaviruses. This enzyme is highly conserved among coronaviruses and is a bifunctional protein with both N7-methyltransferase and 3'-5' exonuclease activities that distinguish nsp14 from its human equivalent. Mutational analysis of SARS-CoV nsp14 highlighted its role in viral replication and translation efficiency of the viral genome. In this paper, we describe the characterization and development of a high-throughput assay for nsp14 utilizing RapidFire technology. The assay has been used to screen a library of 1771 Food and Drug Administration (FDA)-approved drugs. From this, we have validated nitazoxanide as a selective inhibitor of the methyltransferase activity of nsp14. Although modestly active, this compound could serve as a starting point for further optimization.

Mass surveillance in the age of COVID-19.

Epidemiological surveillance programs such as digital contact tracing have been touted as a silver bullet that will free the American public from the strictures of social distancing, enabling a return to school, work, and socializing. This Article assesses whether and under what circumstances the United States ought to embrace such programs. Part I analyzes the constitutionality of programs like digital contact tracing, arguing that the Fourth Amendment's protection against unreasonable searches and seizures may well regulate the use of location data for epidemiological purposes, but that the legislative and executive branches have significant latitude to develop these programs within the broad constraints of the ``special needs'' doctrine elaborated by the courts in parallel circumstances. Part II cautions that the absence of a firm warrant requirement for digital contact tracing should not serve as a green light for unregulated and mass digital location tracking. In light of substantial risks to privacy, policy makers must ask hard questions about efficacy and the comparative advantages of location tracking versus more traditional means of controlling epidemic contagions, take seriously threats to privacy, tailor programs parsimoniously, establish clear metrics for determining success, and set clear plans for decommissioning surveillance programs.