COVID-19: time to rethink palliative care strategy in resource-poor settings

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40 days and 40 nights: Clinical characteristics of major trauma and orthopaedic injury comparing the incubation and lockdown phases of COVID-19 infection

Aims The first death in the UK caused by COVID-19 occurred on 5 March 2020. We aim to describe the clinical characteristics and outcomes of major trauma and orthopaedic patients admitted in the early COVID-19 era. Methods A prospective trauma registry was reviewed at a Level 1 Major Trauma Centre. We divided patients into Group A, 40 days prior to 5 March 2020, and into Group B, 40 days after. Results A total of 657 consecutive trauma and orthopaedic patients were identified with a mean age of 55 years (8 to 98; standard deviation (SD) 22.52) and 393 (59.8%) were males. In all, 344 (approximately 50%) of admissions were major trauma. Group A had 421 patients, decreasing to 236 patients in Group B (36%). Mechanism of injury (MOI) was commonly a fall in 351 (52.4%) patients, but road traffic accidents (RTAs) increased from 56 (13.3%) in group A to 51 (21.6%) in group B (p = 0.030). ICU admissions decreased from 26 (6.2%) in group A to 5 (2.1%) in group B. Overall, 39 patients tested positive for COVID-19 with mean age of 73 years (28 to 98; SD 17.99) and 22 (56.4%) males. Common symptoms were dyspnoea, dry cough, and pyrexia. Of these patients, 27 (69.2%) were nosocomial infections and two (5.1%) of these patients required intensive care unit (ICU) admission with 8/39 mortality (20.5%). Of the patients who died, 50% were older and had underlying comorbidities (hypertension and cardiovascular disease, dementia, arthritis). Conclusion Trauma admissions decreased in the lockdown phase with an increased incidence of RTAs. Nosocomial infection was common in 27 (69.2%) of those with COVID-19. Symptoms and comorbidities were consistent with previous reports with noted inclusion of dementia and arthritis. The mortality rate of trauma and COVID-19 was 20.5%, mainly in octogenarians, and COVID-19 surgical mortality was 15.4%

SARS-CoV-2 variants, spike mutations and immune escape.

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of 'variants of concern', that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets

From COVID-19 research to vaccine application: why might it take 17 months not 17 years and what are the wider lessons?

It is often said that it takes 17 years to move medical research from bench to bedside. In a coronavirus disease (COVID-19) world, such time-lags feel intolerable. In these extraordinary circumstances could years be made into months? If so, could those lessons be used to accelerate medical research when the crisis eases? To measure time-lags in health and biomedical research as well as to identify ways of reducing them, we developed and published (in 2015) a matrix consisting of overlapping tracks (or stages/phases) in the translation from discovery research to developed products, policies and practice. The matrix aids analysis by highlighting the time and actions required to develop research (and its translation) both (1) along each track and (2) from one track to another, e.g. from the discovery track to the research-in-humans track. We noted four main approaches to reducing time-lags, namely increasing resources, working in parallel, starting or working at risk, and improving processes. Examining these approaches alongside the matrix helps interpret the enormous global effort to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of COVID-19. Rapid progress in the discovery/basic and human research tracks is being made through a combination of large-scale funding, work being conducted in parallel (between different teams globally and through working in overlapping tracks), working at greater (but proportionate) risk to safety than usual, and adopting various new processes. The overlapping work of some of the teams involves continuing animal research whilst entering vaccine candidates into Phase I trials alongside planning their Phase II trials. The additional funding available helps to reduce some of the usual financial risks in moving so quickly. Going forward through the increasingly large human trials for safety, dosage and efficacy, it will be vital to overlap work in parallel in the often challenging public policy and clinical tracks. Thus, regulatory and reimbursement bodies are beginning and preparing rapid action to pull vaccines proving to be safe and effective through to extraordinarily rapid application to the general population. Monitoring the development of a COVID-19 vaccine using the matrix (modified as necessary) could help identify which of the approaches speeding development and deployment could be usefully applied more widely in the future.United Kingdom’s Medical Research Council grant MR/K014773/1 ‘Time Lags in the Translation of Medical Research: Developing a Case Study Approach to Achieve a Better Understanding’ from the MRC’s Economic Impact call from the Methodology Research Programme