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1.
Cell Rep Med ; 3(6): 100651, 2022 06 21.
Article in English | MEDLINE | ID: covidwho-1873330

ABSTRACT

Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.


Subject(s)
COVID-19 , T-Lymphocytes , Antibodies, Neutralizing , Antibodies, Viral , Humans , Reinfection , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
2.
Nat Struct Mol Biol ; 29(3): 250-260, 2022 03.
Article in English | MEDLINE | ID: covidwho-1735263

ABSTRACT

The SARS-CoV-2 nonstructural proteins coordinate genome replication and gene expression. Structural analyses revealed the basis for coupling of the essential nsp13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex or RTC) associated with two copies of nsp13 (nsp132-RTC). One copy of nsp13 interacts with the template-RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backward on the RNA template (backtracking), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of nsp13. Here we use cryogenic-electron microscopy and molecular dynamics simulations to analyze the nsp132-RTC, revealing four distinct conformational states of the helicases. The results indicate a mechanism for the nsp132-RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis or backtracking in response to stimuli at the RdRp active site.


Subject(s)
COVID-19 , SARS-CoV-2 , Cryoelectron Microscopy , Humans , RNA Helicases/chemistry , Viral Nonstructural Proteins/chemistry , Virus Replication
3.
Intern Med J ; 2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1731168

ABSTRACT

BACKGROUND: COVID-19 vaccination represents a key preventative part of the Australian public health approach to the SARS-CoV-2 pandemic. Hospital inpatients are frequently high-risk for severe COVID-19 and death. Anecdotes of high-risk inpatients being unvaccinated and a lack of EMR visibility of COVID-19 vaccination status prompted this study as these patients could represent a risk to themselves, staff, other patients and service provision. AIMS: To determine the uptake of COVID-19 vaccine among inpatients at an adult Australian tertiary public hospital and identify reasons for non-vaccination. METHODS: A point-prevalence study of patient-reported COVID-19 vaccine status was conducted on 26th October 2021 via an in-person interview with collection of demographic factors and reasons for non-vaccination. RESULTS: Of 368 (68% of inpatients) participants, 280 (76%) reported receiving at least 1 COVID-19 vaccine dose. Vaccination status was associated with older age, having received the flu vaccine, being born in Australia and not requiring an English-language interpreter. The majority (88%) of participants had at least 1 co-morbid risk factor for severe COVID-19. Of the unvaccinated (n=88), 67% were willing to be vaccinated with 54% of those indicating vaccination in hospital would be helpful and 42% requesting approval from their doctor. CONCLUSIONS: Vaccine uptake in our cohort is sub-optimal. Existing public health programs have failed to reach this high-risk, vulnerable population. Changes to the national vaccination strategy to include a parallel in-hospital program for all hospital encounters and target culturally and linguistically diverse individuals may improve uptake among this high-risk, hard to reach group of patients. This article is protected by copyright. All rights reserved.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323169

ABSTRACT

Background: Duration and quality of immunity to SARS-CoV-2 have significant implications for the management of COVID-19 pandemic. Here, we present a comprehensive set of immunological data from a cohort of individuals (n=43), 12 months after mild COVID-19 disease and in the absence of virus re-exposure.Methods: Serum and PBMC were collected from mild-COVID-19 convalescents 12 months after the COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15). Serum titers of SARS-CoV-2-specific immunoglobulins were quantified by ELISA and virus neutralisation activity was assessed using SARS-CoV-2-Spike pseudovirus particles. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped with an activation-induced marker assay.Findings: In the absence of re-exposure to SARS-CoV-2 Spike- and RBD-specific antibodies were present in 90% of COVID-19 convalescents 12 months post-infection. RBD-specific IgG + memory B cells were maintained in 88.9% of patients, while 62% of patients had serum neutralising activity. Functionally mature memory CD4 + and CD8 + T cells were maintained at frequencies previously reported for earlier time points post-COVID-19, indicating substantial maintenance of durable T cell responses. Interpretations: Immunity to SARS-CoV-2 persists for 12 months in mild COVID-19 convalescent patients that retain high Spike-specific antibody titres, virus neutralisation capacity and circulating RBD-specific memory B cells. Significantly, T cell immunity remained stable 12 months post-infection. This study offers vital information on the duration of natural COVID-19 immunity and its potential protective effect against SARS-CoV-2 reinfection and clinical disease, with clear implications for the ongoing management of the global pandemic. Funding Statement: This work was funded by project grants from The Hospital Research Foundation and Women’s and Children’s Foundation, Adelaide, Australia. This work has been supported by NIH contract 75N9301900065 (A.S, D.W).Declaration of Interests: A.S. is currently a consultant for Gritstone, Flow Pharma, Arcturus, Epitogenesis, Oxfordimmunotech, Caprion and Avalia. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work.Authors PGV, CMH, MGM, AELY, HB, ZAM, ZAD, AA, DA, JG, CF, SO, EMM, DJL, GM, EJG, BAJR, DS, CKL, MRB, DW, RAB, SCB and BGB declare no conflict of interest.Ethics Approval Statement: Study protocols were approved by the Central Adelaide Clinical Human Research Ethics Committee (#13050) and the Women’s and Children’s Health Network Human research ethics (protocol HREC/19/WCHN/65), Adelaide, Australia.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309404

ABSTRACT

An understanding of how infected-susceptible populations interact is critical to identify underlying causal factors and disease transmission patterns of infectious diseases. Disease transmission patterns are dynamic, non-linear, and spatially complex. This anisotropic characteristic of disease spread necessitates the ideal solution to be sensitive to the geographic context. A Spatial Diffusion Model (SDM) to predict interaction potential and COVID-19 risk probability is developed by adapting the Newtonian gravity model. This novel approach overcomes the limitations of existing epidemiological studies by characterizing the behavioral patterns of the infected population to model the spatiotemporal transmission of disease across the geographic space. The proposed model is robust as it couples a multicriteria behavioral pattern to enhance predictive capability. The model shows an 83.74% correlation with the observational COVID-19 case data. The highest risk patterns for COVID-19 are predicted in the neighborhoods of New York City (NYC), exhibiting clustered socioeconomic disparities along with racial and ethnic heterogeneity. Policymakers can use these results to identify neighborhoods at high risk for becoming hot spots;efficiently match community resources with needs, and ensure that the most vulnerable have access to equipment, personnel, and medical interventions. This study emphasizes the need for improved spatial epidemiological models including enhanced depictions of human activity patterns and the need to integrate spatial data with advanced mathematical models.

6.
BMC Med ; 20(1): 26, 2022 01 14.
Article in English | MEDLINE | ID: covidwho-1637129

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. METHODS: We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection. RESULTS: Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. CONCLUSIONS: Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/complications , Humans , Immune System , SARS-CoV-2
7.
Aust N Z J Public Health ; 46(1): 32-35, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1583717

ABSTRACT

OBJECTIVE: To complement the 2020 ANZJPH editorial "How COVID-safe Santa can save Christmas". In addition to a concise update regarding SARS-CoV-2/COVID-19, we aimed to explore some risks of Christmas in terms of adverse health effects, which we call 'Chrishaps'. Our overall study question was "which hazards have been scientifically associated with old Christmas essentials such as decoration, gifts, menus, and Santa himself, as well as new challenges associated with COVID-19?" METHOD: We searched the PubMed, Web of Science, and Open Grey databases systematically and Google unsystematically. RESULTS: Thirty-six pertinent articles - most of them case reports or retrospective analyses - documented Chrishaps. CONCLUSION: Overall results suggested that Chrishaps come in different shapes and guises. Implications for public health: Chrishaps pose a potential minor public health threat that should be borne in mind every festive season. Assessing and discussing specific public health implications of Chrishaps requires systematic risk research to be conducted.


Subject(s)
COVID-19 , Humans , Public Health , Retrospective Studies , SARS-CoV-2
8.
J Bioeth Inq ; 19(1): 7-10, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1529623
9.
J Bioeth Inq ; 18(4): 589-594, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482285

ABSTRACT

We have a responsibility to obey COVID-19 rules, in order to minimize risk. Yet it is still seen as rude to challenge people who do not respect those rules, when in fact the opposite is true; it is rude to increase risk to others. In this paper I analyse the relationship between risk, responsibility, and rudeness by analysing the evolution of the main governmental slogans and rules and explore the complex relationship between simplicity, safety, and perceived fairness of these rules, and how these features in turn influence the extent to which we act responsibly. I begin by exploring the relationship between rudeness and risk in our interactions about coronavirus, before going on to analyse the importance of clear rules in minimizing tension between us, illustrating the argument with various slogans including "stay at home," "stay alert," and the now infamous "rule of six," which is actually at least three different rules. Ultimately, we are faced with a paradox: people annoyed about complex/unfair rules are less likely to obey them, even if that means rules will apply for longer and even though it was noncompliance with earlier simpler rules that means new rules are necessary. And if rules make less or no sense it is harder to try to get people to follow them in your own capacity as a citizen; it is hard to police rules that are seen as arbitrary or unfair.


Subject(s)
COVID-19 , Incivility , Humans , Loneliness , SARS-CoV-2 , Social Behavior
10.
J Med Ethics ; 2021 Jun 08.
Article in English | MEDLINE | ID: covidwho-1262406

ABSTRACT

One of the many problems posed by the collective effort to tackle COVID-19 is non-compliance with restrictions. Some people would like to obey restrictions but cannot due to their job or other life circumstances; others are not good at following rules that restrict their liberty, even if the potential consequences of doing so are repeatedly made very clear to them. Among this group are a minority who simply do not care about the consequences of their actions. But many others fail to accurately perceive the harms that they might be causing. One of the main reasons for this is that the harms done by transmitting COVID-19 to someone else are morally distant from the agent, particularly in cases where infection is asymptomatic. In this paper, I describe seven different aspects of moral distance in the context of COVID-19, explore how they affect (lack of) motivation to obey restrictions, and suggest several ways in which such moral distance can be reduced - primarily through enhanced-contact tracing that makes it clear to individuals and the public precisely who they could be harming and how.

11.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1254144

ABSTRACT

Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking. We use cryo-electron microscopy, RNA-protein cross-linking, and unbiased molecular dynamics simulations to characterize SARS-CoV-2 RdRp backtracking. The results establish that the single-stranded 3' segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3' end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking. Backtracking may aid proofreading, a crucial process for SARS-CoV-2 resistance against antivirals.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , Virus Replication/genetics , Adenosine Monophosphate/pharmacology , Antiviral Agents/pharmacology , COVID-19/genetics , COVID-19/metabolism , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Cryoelectron Microscopy/methods , DNA Helicases/metabolism , Genome, Viral , Humans , Molecular Dynamics Simulation , RNA Helicases/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Dependent RNA Polymerase/metabolism , RNA-Dependent RNA Polymerase/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics
12.
Lancet Digit Health ; 3(6): e360-e370, 2021 06.
Article in English | MEDLINE | ID: covidwho-1240696

ABSTRACT

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. METHODS: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. FINDINGS: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded. INTERPRETATION: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. FUNDING: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).


Subject(s)
Bacterial Infections/epidemiology , COVID-19 , Respiratory Tract Infections/epidemiology , Bacterial Infections/transmission , COVID-19/prevention & control , Haemophilus influenzae , Humans , Incidence , Interrupted Time Series Analysis , Neisseria meningitidis , Population Surveillance , Prospective Studies , Public Health Practice , Streptococcus agalactiae , Streptococcus pneumoniae
13.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1196910

ABSTRACT

Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking. We use cryo-electron microscopy, RNA-protein cross-linking, and unbiased molecular dynamics simulations to characterize SARS-CoV-2 RdRp backtracking. The results establish that the single-stranded 3' segment of the product RNA generated by backtracking extrudes through the RdRp nucleoside triphosphate (NTP) entry tunnel, that a mismatched nucleotide at the product RNA 3' end frays and enters the NTP entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking. Backtracking may aid proofreading, a crucial process for SARS-CoV-2 resistance against antivirals.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , Virus Replication/genetics , Adenosine Monophosphate/pharmacology , Antiviral Agents/pharmacology , COVID-19/genetics , COVID-19/metabolism , Coronavirus RNA-Dependent RNA Polymerase/metabolism , Cryoelectron Microscopy/methods , DNA Helicases/metabolism , Genome, Viral , Humans , Molecular Dynamics Simulation , RNA Helicases/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Dependent RNA Polymerase/metabolism , RNA-Dependent RNA Polymerase/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics
14.
Camb Q Healthc Ethics ; 30(2): 255-261, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1149657

ABSTRACT

We all now know that the novel coronavirus is anything but a common cold. The pandemic has created many new obligations for all of us, several of which come with serious costs to our quality of life. But in some cases, the guidance and the law are open to a degree of interpretation, leaving us to decide what is the ethical (or unethical but desired) course of action. Because of the high cost of some of the obligations, a conflict of interest can arise between what we want to do and what it is right to do. And so, some people choose to respect only the letter of the law, but not the spirit, or not to respect even the spirit of the guidelines. This paper identifies and describes the new obligations imposed on us all by the pandemic, considers their costs in terms of the good life, and provides an ethical analysis of two personal and two public cases in terms of the letter and spirit of the guidance and legislation.


Subject(s)
COVID-19/prevention & control , Ethical Analysis , Government Regulation , Moral Obligations , Quarantine/ethics , Communicable Disease Control/legislation & jurisprudence , Humans , Quarantine/legislation & jurisprudence , United Kingdom
15.
Bioethics ; 35(4): 380-384, 2021 05.
Article in English | MEDLINE | ID: covidwho-1124656

ABSTRACT

Much of the ethical discourse concerning the coronavirus pandemic has focused on the allocation of scarce resources, be it potentially beneficial new treatments, ventilators, intensive care beds, or oxygen. Somewhat ironically, the more important ethical issues may lie elsewhere, just as the more important medical issues do not concern intensive care or treatment for COVID-19 patients, but rather the diversion towards these modes of care at the expense of non-Covid patients and treatment. In this article I explore how ethicists can and should prioritize which ethical issues to deal with, and develop a method of triage for identification and prioritization of ethical issues both in the next public health emergency and in bioethics more widely.


Subject(s)
Bioethical Issues , COVID-19 , Ethicists , Health Priorities/ethics , Humans , Research/standards , SARS-CoV-2
16.
Intern Med J ; 51(1): 42-51, 2021 01.
Article in English | MEDLINE | ID: covidwho-944728

ABSTRACT

BACKGROUND: On 31 December 2019, the World Health Organization recognised clusters of pneumonia-like cases due to a novel coronavirus disease (COVID-19). COVID-19 became a pandemic 71 days later. AIM: To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID-19 in Australia. METHODS: This is a retrospective, multi-centre case series. All patients with confirmed COVID-19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. RESULTS: The median age of the patient cohort was 42 years (interquartile range (IQR), 24-53 years) with six men and five women. Eight (72.7%) patients had returned from Wuhan, one from Shenzhen, one from Japan and one from Europe. Possible human-to-human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co-morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75-21), all patients were discharged. CONCLUSIONS: This is a historical record of the first COVID-19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID-19 models of care and informing the management of COVID-19 over time as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection.


Subject(s)
COVID-19/epidemiology , Adult , Australia/epidemiology , COVID-19/therapy , Female , Humans , Male , Middle Aged , Patient Discharge , Retrospective Studies , Tertiary Care Centers , Young Adult
17.
Medicine and Law ; 39(2):249-267, 2020.
Article in English | Web of Science | ID: covidwho-838920

ABSTRACT

Whereas the heart of the purpose and activity of the European Union is concerned with economic harmonisation, its internal market, and the freedom of movement of people, goods, services, and capital, necessarily require public health measures. The EU is committed to both human rights and to "Health in All Policies". This paper considers how that agenda has been confronted by the COVID-19 pandemic. It considers how the EU Treaties limit the possible scope of that response. The paper considers responses in relation to freedom of movement, the work of the European Centre for Disease Prevention and Control, issues relating to the operation of the General Data Protection Regulation, and the Clinical Trials Directive and Medical Devices Directive. It concludes with a brief examination of the economic responses of the EU to the COVID-19 pandemic. An Appendix gives a brief introduction to EU (health) law and history.

18.
J. Intensive Care Soc. ; 2020.
Article in English | WHO COVID, ELSEVIER | ID: covidwho-736344

ABSTRACT

CRITCON-Pandemic levels with an associated operational responsibility matrix were recently published by the Intensive Care Society as a modification to Winter Flu CRITCON levels, to better account for differences between a winter flu surge in critical care activity and the capacity challenges of the COVID-19 pandemic. In this paper, we propose an expansion and explanation of the operational matrix to suggest a stepwise ethical approach to clinician responsibility. We propose and outline the main ethical risks created at each level and discuss how those risks can be mitigated through a balanced application of the predominant ethical principle which in turn provides practical guidance to clinician responsibility. We thus seek to specify the ethical and legal principles that should be used in applying the operational matrix, and what the practical effects could be.

20.
Chronobiol Int ; 37(7): 1115-1117, 2020 07.
Article in English | MEDLINE | ID: covidwho-635180

ABSTRACT

With countless "natural" experiments triggered by the COVID-19-associated physical distancing, one key question comes from chronobiology: "When confined to homes, how does the reduced exposure to natural daylight arising from the interruption of usual outdoor activities plus lost temporal organization ordinarily provided from workplaces and schools affect the circadian timing system (the internal 24 h clock) and, consequently, health of children and adults of all ages?" Herein, we discuss some ethical and scientific facets of exploring such natural experiments by offering a hypothetical case study of circadian biology.


Subject(s)
Betacoronavirus/pathogenicity , Circadian Rhythm/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Adult , COVID-19 , Child , Humans , Light , Pandemics , SARS-CoV-2 , Sleep/physiology
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