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1.
English Academy Review ; : 1-14, 2023.
Article in English | Taylor & Francis | ID: covidwho-2212438
2.
Elife ; 112022 09 13.
Article in English | MEDLINE | ID: covidwho-2217486

ABSTRACT

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated. Results: A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources. Conclusions: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days. Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. Clinical trial number: NCT04405934.


Subject(s)
COVID-19 , Cross Infection , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/prevention & control , Prospective Studies , Infection Control/methods , Cross Infection/epidemiology , Cross Infection/prevention & control , Hospitals
3.
J Bioeth Inq ; 19(2): 191-202, 2022 06.
Article in English | MEDLINE | ID: covidwho-1906501

ABSTRACT

Human connection is universally important, particularly in the context of serious illness and at the end of life. The presence of close family and friends has many benefits when death is close. Hospital visitation restrictions during the Coronavirus (COVID-19) pandemic therefore warrant careful consideration to ensure equity, proportionality, and the minimization of harm. The Australian and New Zealand Society for Palliative Medicine COVID-19 Special Interest Group utilized the relevant ethical and public health principles, together with the existing disease outbreak literature and evolving COVID-19 knowledge, to generate a practical framework of visiting restrictions for inpatients receiving palliative and end-of-life care. Expert advice from an Infectious Diseases physician ensured relevance to community transmission dynamics. Three graded levels of visitor restrictions for inpatient settings are proposed, defining an appropriate level of minimum access. These depend upon the level of community transmission of COVID-19, the demand on health services, the potential COVID-19 status of the patient and visitors, and the imminence of the patient's death. This framework represents a cohesive, considered, proportionate, and ethically robust approach to improve equity and consistency for inpatients receiving palliative care during the COVID-19 pandemic and may serve as a template for future disease outbreaks.


Subject(s)
COVID-19 , Australia , COVID-19/epidemiology , Humans , Inpatients , Palliative Care , Pandemics
4.
Am Surg ; 88(7): 1689-1693, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1892040

ABSTRACT

BACKGROUND: Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The "death diamond" (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile. METHODS: A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined. RESULTS: A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient. DISCUSSION: The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.


Subject(s)
Blood Coagulation Disorders , Wounds and Injuries , Biomarkers , Humans , Retrospective Studies , Thrombelastography/methods , Trauma Centers , Wounds and Injuries/diagnosis , Wounds and Injuries/therapy
5.
Med J Aust ; 216(4): 203-208, 2022 Mar 07.
Article in English | MEDLINE | ID: covidwho-1551800

ABSTRACT

INTRODUCTION: Older people living with frailty and/or cognitive impairment who have coronavirus disease 2019 (COVID-19) experience higher rates of critical illness. There are also people who become critically ill with COVID-19 for whom a decision is made to take a palliative approach to their care. The need for clinical guidance in these two populations resulted in the formation of the Care of Older People and Palliative Care Panel of the National COVID-19 Clinical Evidence Taskforce in June 2020. This specialist panel consists of nursing, medical, pharmacy and allied health experts in geriatrics and palliative care from across Australia. MAIN RECOMMENDATIONS: The panel was tasked with developing two clinical flow charts for the management of people with COVID-19 who are i) older and living with frailty and/or cognitive impairment, and ii) receiving palliative care for COVID-19 or other underlying illnesses. The flow charts focus on goals of care, communication, medication management, escalation of care, active disease-directed care, and managing symptoms such as delirium, anxiety, agitation, breathlessness or cough. The Taskforce also developed living guideline recommendations for the care of adults with COVID-19, including a commentary to discuss special considerations when caring for older people and those requiring palliative care. CHANGES IN MANAGEMENT AS RESULT OF THE GUIDELINE: The practice points in the flow charts emphasise quality clinical care, with a focus on addressing the most important challenges when caring for older individuals and people with COVID-19 requiring palliative care. The adult recommendations contain additional considerations for the care of older people and those requiring palliative care.


Subject(s)
COVID-19/therapy , Palliative Care/standards , Aged , Australia , Humans
6.
Int J Infect Dis ; 114: 178-182, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1487753

ABSTRACT

This article reports a case of a 21-year-old woman with refractory B-cell acute lymphocytic leukaemia who presented with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). She remained positive for SARS-CoV-2 by viral culture for 78 days and by polymerase chain reaction (PCR) for 97 days. Sequencing of repeat samples over time demonstrated an increasing and dynamic repertoire of mutations.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Female , Humans , Immunocompromised Host , Mutation , Virus Shedding , Young Adult
7.
J Bioeth Inq ; 17(4): 461-463, 2020 12.
Article in English | MEDLINE | ID: covidwho-1384575
8.
Elife ; 102021 08 13.
Article in English | MEDLINE | ID: covidwho-1357606

ABSTRACT

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within- and between-host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.


The COVID-19 pandemic has had major health impacts across the globe. The scientific community has focused much attention on finding ways to monitor how the virus responsible for the pandemic, SARS-CoV-2, spreads. One option is to perform genetic tests, known as sequencing, on SARS-CoV-2 samples to determine the genetic code of the virus and to find any differences or mutations in the genes between the viral samples. Viruses mutate within their hosts and can develop into variants that are able to more easily transmit between hosts. Genetic sequencing can reveal how genetically similar two SARS-CoV-2 samples are. But tracking how SARS-CoV-2 moves from one person to the next through sequencing can be tricky. Even a sample of SARS-CoV-2 viruses from the same individual can display differences in their genetic material or within-host variants. Could genetic testing of within-host variants shed light on factors driving SARS-CoV-2 to evolve in humans? To get to the bottom of this, Tonkin-Hill, Martincorena et al. probed the genetics of SARS-CoV-2 within-host variants using 1,181 samples. The analyses revealed that 95.1% of samples contained within-host variants. A number of variants occurred frequently in many samples, which were consistent with mutational hotspots in the SARS-CoV-2 genome. In addition, within-host variants displayed mutation patterns that were similar to patterns found between infected individuals. The shared within-host variants between samples can help to reconstruct transmission chains. However, the observed mutational hotspots and the detection of multiple strains within an individual can make this challenging. These findings could be used to help predict how SARS-CoV-2 evolves in response to interventions such as vaccines. They also suggest that caution is needed when using information on within-host variants to determine transmission between individuals.


Subject(s)
COVID-19/genetics , COVID-19/physiopathology , Genetic Variation , Genome, Viral , Host-Pathogen Interactions/genetics , Mutation , SARS-CoV-2/genetics , Base Sequence , Humans , Pandemics , Phylogeny
9.
Genome Biol ; 22(1): 196, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1295478

ABSTRACT

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.


Subject(s)
Cloud Computing , Genomics/organization & administration , SARS-CoV-2/genetics , COVID-19/epidemiology , Epidemiological Monitoring , Genome, Viral , Humans , Sequence Analysis, DNA , United Kingdom , User-Computer Interface , Whole Genome Sequencing
10.
Elife ; 102021 03 02.
Article in English | MEDLINE | ID: covidwho-1112865

ABSTRACT

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Nursing Homes , SARS-CoV-2/genetics , Aged, 80 and over , COVID-19/virology , Disease Outbreaks , England/epidemiology , Female , Humans , Infectious Disease Transmission, Patient-to-Professional , Infectious Disease Transmission, Professional-to-Patient , Male , Polymorphism, Single Nucleotide , Sequence Analysis , Time Factors
11.
J Bioeth Inq ; 17(4): 761-765, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-728238

ABSTRACT

Among the far-reaching impacts of COVID-19 is its impact on care systems, the social and other systems that we rely on to maintain and provide care for those with "illness." This paper will examine these impacts through a description of the influence on palliative care systems that have arisen within this pandemic. It will explore the impact on the meaning of care, how care is performed and identified, and the responses of palliative care systems to these challenges. It will also highlight the current and potential future implications of these dynamics within the unfolding crisis of this pandemic.


Subject(s)
COVID-19 , Delivery of Health Care , Palliative Care , Pandemics , Humans , SARS-CoV-2
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