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Showing papers by "University of Oxford published in 2022"


Journal ArticleDOI
Yaning Lin1
TL;DR: In this article , the authors compared the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes and found that outbreaks of the Delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variants.
Abstract: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17-43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32-3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08-1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47-8·05] and for hospital admission or emergency care attendance 1·58 [0·69-3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29-4·16] and 1·43 [1·04-1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

447 citations


Journal ArticleDOI
TL;DR: Zahradník et al. as discussed by the authors reported that omicron is highly transmissible, in a population where 60% already show serological evidence of previous infection or vaccination; although early reports do not indicate more severe disease.

263 citations


Journal ArticleDOI
TL;DR: In this paper , the authors investigated the severity of omicron and the extent to which booster vaccines are effective in preventing symptomatic infection using a nested test-negative design incident case-control study covering the period Nov 1-Dec 19, 2021.
Abstract: Since its emergence in November, 2021, in southern Africa, the SARS-CoV-2 omicron variant of concern (VOC) has rapidly spread across the world. We aimed to investigate the severity of omicron and the extent to which booster vaccines are effective in preventing symptomatic infection.In this study, using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, we did a cohort analysis with a nested test-negative design incident case-control study covering the period Nov 1-Dec 19, 2021, to provide initial estimates of omicron severity and the effectiveness of vaccine boosters against symptomatic disease relative to 25 weeks or more after the second vaccine dose. Primary care data derived from 940 general practices across Scotland were linked to laboratory data and hospital admission data. We compared outcomes between infection with the delta VOC (defined as S-gene positive) and the omicron VOC (defined as S-gene negative). We assessed effectiveness against symptomatic SARS-CoV-2 infection, with infection confirmed through a positive RT-PCR.By Dec 19, 2021, there were 23 840 S-gene-negative cases in Scotland, which were predominantly among those aged 20-39 years (11 732 [49·2%]). The proportion of S-gene-negative cases that were possible reinfections was more than ten times that of S-gene-positive cases (7·6% vs 0·7%; p<0·0001). There were 15 hospital admissions in S-gene-negative individuals, giving an adjusted observed-to-expected admissions ratio of 0·32 (95% CI 0·19-0·52). The booster vaccine dose was associated with a 57% (54-60) reduction in the risk of symptomatic S-gene-negative infection relative to individuals who tested positive 25 weeks or more after the second vaccine dose.These early national data suggest that omicron is associated with a two-thirds reduction in the risk of COVID-19 hospitalisation compared with delta. Although offering the greatest protection against delta, the booster dose of vaccination offers substantial additional protection against the risk of symptomatic COVID-19 for omicron compared with 25 weeks or more after the second vaccine dose.Health Data Research UK, National Core Studies, Public Health Scotland, Scottish Government, UK Research and Innovation, and University of Edinburgh.

160 citations


Journal ArticleDOI
Tracy Hussell1, Ramsey Sabit2, Rachel Upthegrove3, Daniel M. Forton4  +524 moreInstitutions (270)
TL;DR: The Post-hospitalisation COVID-19 study (PHOSP-COVID) as mentioned in this paper is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID19 across the UK.

118 citations


Posted ContentDOI
TL;DR: In this article, a discussion of measurement uncertainty associated with surveillance of wastewater, focusing on lessons-learned from the UK programmes monitoring COVID-19 is presented, showing that sources of uncertainty impacting measurement quality and interpretation of data for public health decision-making, are varied and complex.

86 citations


Journal ArticleDOI
25 Mar 2022-Science
TL;DR: In this article , the authors analyzed the prevalence of SARS-CoV-2 and its dynamics in England from the end of November to mid-December 2021 among almost 100,000 participants in the REACT-1 study.
Abstract: The unprecedented rise in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed the prevalence of SARS-CoV-2 and its dynamics in England from the end of November to mid-December 2021 among almost 100,000 participants in the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, with an increasing proportion of infections due to Omicron. We observed large decreases in swab positivity among mostly vaccinated older children (12 to 17 years) relative to unvaccinated younger children (5 to 11 years), and in adults who received a third (booster) vaccine dose versus two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.

84 citations


Journal ArticleDOI
01 Jul 2022
TL;DR: Mulembakani et al. as discussed by the authors reported a major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo, with most cases restricted to endemic areas.
Abstract: Monkeypox virus was first documented in humans in the 1970s and outbreaks have been reported in many countries, with most cases restricted to endemic areas.1Rimoin AW Mulembakani PM Johnston SC et al.Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo.Proc Natl Acad Sci USA. 2010; 107: 16 262-16 267Crossref Scopus (246) Google Scholar In early May, 2022, monkeypox cases were reported in the UK, Spain, and elsewhere in Europe (figure, appendix).2UK Health Security AgencyMonkeypox cases confirmed in England—latest updates.https://www.gov.uk/government/news/monkeypox-cases-confirmed-in-england-latest-updatesDate: May 14, 2022Date accessed: May 25, 2022Google Scholar The pattern of geographical dispersal was much larger compared with past outbreaks that were more localised and occurred often in under-resourced communities.3Nakoune E Olliaro P Waking up to monkeypox.BMJ. 2022; 377o1321PubMed Google Scholar The size of the outbreak clusters is growing each day, as is the geographical spread across Europe and North America. Within the first week of the initial report, 24 countries reported suspected and confirmed cases of monkeypox virus, some of which had known travel links to the UK, Spain, Canada, and western Europe. As of June 5, 2022, there have been 920 confirmed and 70 suspected cases. Of 64 confirmed cases with known travel history, 32 were associated with travel from Europe, three from west Africa, two from Canada, and one from Australia. For 26 cases, travel history locations remain unknown. WHO convened a meeting of experts and technical advisory groups on May 20, 2022,4WHOWHO working closely with countries responding to monkeypox.https://www.who.int/news/item/20-05-2022-who-working-closely-with-countries-responding-to-monkeypoxDate: May 20, 2022Date accessed: May 25, 2022Google Scholar to investigate the causes of the outbreak and have released updated guidance on surveillance, case investigation, and contact tracing.5WHOSurveillance, case investigation and contact tracing for monkeypox.https://www.who.int/publications/i/item/WHO-MPX-surveillance-2022.1Date: May 22, 2022Date accessed: May 25, 2022Google Scholar The reason for the outbreak having a broader geographical reach is being investigated by the international and national public health community and the research community, contributing to a finer scale understanding of the outbreak dynamics. However, cessation of smallpox vaccination programmes, encroachment of humans into forested areas, and growing international mobility seem to be playing important roles in the epidemiology of monkeypox virus outbreaks.6Bunge EM Hoet B Chen L et al.The changing epidemiology of human monkeypox—a potential threat? A systematic review.PLoS Negl Trop Dis. 2022; 16e0010141Crossref PubMed Scopus (75) Google Scholar To support global response efforts, our team created an open-access database and visualisation to track the occurrence of cases in different countries. In addition, where available, we added information on age (aggregated into age ranges, with a minimum range of 5 years), gender, dates of symptom onset and laboratory confirmation, symptoms, locations (aggregated to the state level), travel history, and additional metadata defined by WHO.5WHOSurveillance, case investigation and contact tracing for monkeypox.https://www.who.int/publications/i/item/WHO-MPX-surveillance-2022.1Date: May 22, 2022Date accessed: May 25, 2022Google Scholar Data are compiled from verified sources, including reports from governments and public health organisations and news media reporting of health official statements. As verified information and official statements are published, we document secondary sources and update the metadata in the dataset. An on-call schedule for curators that runs 24 h a day, 7 days a week was established to ensure data are updated in near real-time. Each case is seen and discussed by at least two curators before being made available via our Global.health GitHub repository, and pushed to the map visualisation at least four times per day. During the early stages of outbreaks, obtaining reliable, synthesised data on the characteristics of cases is a challenge, especially at a global scale. Our work attempts to harmonise information across countries and provide additional data to support the epidemiological understanding of the origins and transmission dynamics of this outbreak. Ideally, these data are paired with virus genomic data and integrated directly with countries' epidemiological line-list data. In our repository, we are also working with colleagues and the WHO Hub for Pandemic and Epidemic Intelligence to define a contact data schema allowing countries and researchers to estimate and re-estimate key epidemiological parameters, such as the incubation period and serial interval, across different settings. Real-time data are necessary to plan effective control measures should this outbreak grow further. The work builds on infrastructure developed for epidemic control and pandemic preparedness and was used for the COVID-19 pandemic.7Kraemer MUG Scarpino SV Marivate V et al.Data curation during a pandemic and lessons learned from COVID-19.Nat Comput Sci. 2021; 1: 9-10Crossref Scopus (10) Google Scholar Global efforts are needed to ensure similar efforts to rapidly harmonise and publish detailed epidemiological data are supported during future outbreaks of emerging and re-emerging pathogens. This example will be a learning pathway to build better surveillance systems globally. MUGK and JSB report funding from The Rockefeller Foundation and Google.org. TdO received fees from Illumina as a member of the Infectious Disease Testing Advisory Board and received partial travel support to attend the Nobel Symposium of Medicine in May, 2022. IIB received consulting fees from BlueDot and NHL Players' Association. All other authors declare no competing interests. Download .pdf (2.09 MB) Help with pdf files Supplementary appendix

83 citations


Journal ArticleDOI
TL;DR: In this paper, the authors explore how plastic contributes to greenhouse gas (GHG) emissions from the beginning to the end of its life cycle, and show that more extreme weather and floods associated with climate change, will exacerbate the spread of plastic in the natural environment.

76 citations


Journal ArticleDOI
TL;DR: In this article , a bi-level scheduling model is proposed for isolated micro-grids with consideration of multi-stakeholders, where the lower and upper level models respectively aim to the minimization of user cost and microgrid operational cost under real-time electricity pricing environments.

69 citations


Journal ArticleDOI
TL;DR: In this paper , a systematic review and network meta-analysis was conducted to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.

53 citations


Journal ArticleDOI
TL;DR: In this article, a review of face-centred cubic CrMnFeCoNi, also known as the Cantor alloy, and the irradiation response of the Cantor Alloy and its sub-systems is presented.

Journal ArticleDOI
TL;DR: Aquaporins facilitate the passive transport of water, solutes, or ions across biological membranes as discussed by the authors and are implicated in diverse pathologies including brain edema following stroke or trauma, epilepsy, cancer cell migration and tumor angiogenesis, metabolic disorders, and inflammation.

Journal ArticleDOI
TL;DR: Raman spectroscopy combined with machine learning techniques provides a rapid method for breast cancer analysis able to reveal differences in intracellular compositions and molecular structures among subtypes.

Journal ArticleDOI
Tito Magri1
TL;DR: In this article , a wide range of cognitive functions critical for daily life (including sustained attention, memory, motor control, planning, semantic reasoning, mental rotation and spatial-visual attention) in people who had previously suffered from COVID-19 but were not significantly different from a control group on self-reported fatigue, forgetfulness, sleep abnormality, motivation, depression, anxiety and personality profile.
Abstract: Abstract Recent studies indicate that COVID-19 infection can lead to serious neurological consequences in a small percentage of individuals. However, in the months following acute illness, many more suffer from fatigue, low motivation, disturbed mood, poor sleep and cognitive symptoms, colloquially referred to as ‘brain fog’. But what about individuals who had asymptomatic to moderate COVID-19 and reported no concerns after recovering from COVID-19? Here, we examined a wide range of cognitive functions critical for daily life (including sustained attention, memory, motor control, planning, semantic reasoning, mental rotation and spatial–visual attention) in people who had previously suffered from COVID-19 but were not significantly different from a control group on self-reported fatigue, forgetfulness, sleep abnormality, motivation, depression, anxiety and personality profile. Reassuringly, COVID-19 survivors performed well in most abilities tested, including working memory, executive function, planning and mental rotation. However, they displayed significantly worse episodic memory (up to 6 months post-infection) and greater decline in vigilance with time on task (for up to 9 months). Overall, the results show that specific chronic cognitive changes following COVID-19 are evident on objective testing even amongst those who do not report a greater symptom burden. Importantly, in the sample tested here, these were not significantly different from normal after 6–9 months, demonstrating evidence of recovery over time.

Journal ArticleDOI
TL;DR: A review of the literature on the trafficking of mammalian aquaporins with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis is presented in this paper .
Abstract: The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating the diffusion of small polar solutes. AQPs have been recognised as drug targets for a variety of disorders associated with disrupted water or solute transport, including brain oedema following stroke or trauma, epilepsy, cancer cell migration and tumour angiogenesis, metabolic disorders, and inflammation. Despite this, drug discovery for AQPs has made little progress due to a lack of reproducible high-throughput assays and difficulties with the druggability of AQP proteins. However, recent studies have suggested that targetting the trafficking of AQP proteins to the plasma membrane is a viable alternative drug target to direct inhibition of the water-conducting pore. Here we review the literature on the trafficking of mammalian AQPs with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis.

Journal ArticleDOI
TL;DR: The authors found that the share of tasks that can be done from home varies considerably both across as well as within occupations and industries, and that women and workers with less stable work arrangements can do fewer tasks from home.

Journal ArticleDOI
TL;DR: In this article , the authors investigated the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID19 outcomes after vaccination by using a large, representative population-based cohort from England.


Journal ArticleDOI
21 Jan 2022-Cells
TL;DR: In this article , the authors explored the main sources and consequences of age-associated inflammation in the context of immunosenescence and highlighted potential interventions to improve later life health, including diet, exercise, and pharmacological interventions.
Abstract: Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately lead to the recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from the continued presence of the initial trigger, or the dysfunction of signalling and/or effector pathways, is harmful to health. While successful ageing in older adults, including centenarians, is associated with low levels of inflammation, elevated inflammation increases the risk of poor health and death. Hence inflammation has been described as one of seven pillars of ageing. Age-associated sterile, chronic, and low-grade inflammation is commonly termed inflammageing-it is not simply a consequence of increasing chronological age, but is also a marker of biological ageing, multimorbidity, and mortality risk. While inflammageing was initially thought to be caused by "continuous antigenic load and stress", reports from the last two decades describe a much more complex phenomenon also involving cellular senescence and the ageing of the immune system. In this review, we explore some of the main sources and consequences of inflammageing in the context of immunosenescence and highlight potential interventions. In particular, we assess the contribution of cellular senescence to age-associated inflammation, identify patterns of pro- and anti-inflammatory markers characteristic of inflammageing, describe alterations in the ageing immune system that lead to elevated inflammation, and finally assess the ways that diet, exercise, and pharmacological interventions can reduce inflammageing and thus, improve later life health.

Journal ArticleDOI
Emma Ladds1
01 Feb 2022-BMJ Open
TL;DR: A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up was carried out by as discussed by the authors to explore the lived experience of "brain fog", the wide variety of neurocognitive symptoms that can follow COVID-19.
Abstract: To explore the lived experience of 'brain fog'-the wide variety of neurocognitive symptoms that can follow COVID-19.A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up.50 participants were recruited from a previous qualitative study of the lived experience of long COVID-19 (n=23) and online support groups for people with persistent neurocognitive symptoms following COVID-19 (n=27). In remotely held focus groups, participants were invited to describe their neurocognitive symptoms and comment on others' accounts. Individuals were followed up by email 4-6 months later. Data were audiotaped, transcribed, anonymised and coded in NVIVO. They were analysed by an interdisciplinary team with expertise in general practice, clinical neuroscience, the sociology of chronic illness and service delivery, and checked by people with lived experience of brain fog.Of the 50 participants, 42 were female and 32 white British. Most had never been hospitalised for COVID-19. Qualitative analysis revealed the following themes: mixed views on the appropriateness of the term 'brain fog'; rich descriptions of the experience of neurocognitive symptoms (especially executive function, attention, memory and language), accounts of how the illness fluctuated-and progressed over time; the profound psychosocial impact of the condition on relationships, personal and professional identity; self-perceptions of guilt, shame and stigma; strategies used for self-management; challenges accessing and navigating the healthcare system; and participants' search for physical mechanisms to explain their symptoms.These qualitative findings complement research into the epidemiology and mechanisms of neurocognitive symptoms after COVID-19. Services for such patients should include: an ongoing therapeutic relationship with a clinician who engages with their experience of neurocognitive symptoms in its personal, social and occupational context as well as specialist services that include provision for neurocognitive symptoms, are accessible, easily navigable, comprehensive and interdisciplinary.

Journal ArticleDOI
TL;DR: In this paper , the effects of cohesin and CTCF depletion on chromatin architecture were investigated and it was shown that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.
Abstract: Abstract Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date (20 bp resolution) and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis -regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.

Journal ArticleDOI
TL;DR: In this paper , the authors analyse the underlying dynamics driving patterns in SARS-CoV-2 prevalence during September, 2021, in England, using RT-PCR swab positivity data from 100 527 participants with valid throat and nose swabs in round 14 of REACT-1.

Journal ArticleDOI
31 Mar 2022
TL;DR: In this paper, the authors provide a foundation for future research in process mining with respect to privacy and confidentiality requirements, which are very important prerequisites for applying process mining to comply with regulations and keep company secrets.
Abstract: Privacy and confidentiality are very important prerequisites for applying process mining to comply with regulations and keep company secrets. This article provides a foundation for future research ...

Journal ArticleDOI
TL;DR: The role of situational factors are revealed in the anticipated eating of a variety of novel/unfamiliar foods, thus providing practical implications on how/where to introduce such foods or engineer appropriate situations to increase the acceptance of, and exposure to, such novels.

Journal ArticleDOI
TL;DR: Aerosol-cloud interactions (ACI) are considered to be the most uncertain driver of present-day radiative forcing due to human activities as discussed by the authors , and using correlations to infer causality can be challenging when meteorological variability also drives both aerosol and cloud changes independently.
Abstract: Aerosol-cloud interactions (ACIs) are considered to be the most uncertain driver of present-day radiative forcing due to human activities. The nonlinearity of cloud-state changes to aerosol perturbations make it challenging to attribute causality in observed relationships of aerosol radiative forcing. Using correlations to infer causality can be challenging when meteorological variability also drives both aerosol and cloud changes independently. Natural and anthropogenic aerosol perturbations from well-defined sources provide "opportunistic experiments" (also known as natural experiments) to investigate ACI in cases where causality may be more confidently inferred. These perturbations cover a wide range of locations and spatiotemporal scales, including point sources such as volcanic eruptions or industrial sources, plumes from biomass burning or forest fires, and tracks from individual ships or shipping corridors. We review the different experimental conditions and conduct a synthesis of the available satellite datasets and field campaigns to place these opportunistic experiments on a common footing, facilitating new insights and a clearer understanding of key uncertainties in aerosol radiative forcing. Cloud albedo perturbations are strongly sensitive to background meteorological conditions. Strong liquid water path increases due to aerosol perturbations are largely ruled out by averaging across experiments. Opportunistic experiments have significantly improved process-level understanding of ACI, but it remains unclear how reliably the relationships found can be scaled to the global level, thus demonstrating a need for deeper investigation in order to improve assessments of aerosol radiative forcing and climate change.

Journal ArticleDOI
TL;DR: In this paper, 16S rRNA sequencing and network analysis were used for deciphering the co-occurrence patterns of bacterial communities in two different types of soil profiles around a typical Tl-bearing pyrite mine.

Journal ArticleDOI
TL;DR: In this paper , a review aimed to describe how anxiety and post-traumatic stress (PTS) are defined and assessed, and to estimate anxiety and PTS prevalence among parents of babies admitted to Neonatal units (NNU).

Journal ArticleDOI
TL;DR: In this article, the Research Grants Council of Hong Kong Special Administrative Region, China (Project No. UGC/FDS15/E01/18) has proposed a research grant scheme for the Hong Kong SAR.

Posted ContentDOI
18 Jan 2022
TL;DR: In a UK community study, loss of taste/smell was markedly less commonly reported with Omicron BA.2 than Delta SARS-CoV-2 infections, with smaller declines in reported shortness of breath, myalgia and fatigue/weakness, but increases in sore throat, challenging symptom-based testing algorithms as mentioned in this paper .
Abstract: ABSTRACT Background The SARS-CoV-2 Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other co-circulating respiratory viruses. Methods In a nationally representative UK community study, the COVID-19 Infection Survey, we investigated symptoms in PCR-positive infection episodes vs. PCR-negative study visits over calendar time, by age and vaccination status, comparing periods when the Delta, Omicron BA.1 and BA.2 variants were dominant. Results Between October-2020 and April-2022, 120,995 SARS-CoV-2 PCR-positive episodes occurred in 115,886 participants, with 70,683 (58%) reporting symptoms. The comparator comprised 4,766,366 PCR-negative study visits (483,894 participants); 203,422 (4%) reporting symptoms. Symptom reporting in PCR-positives varied over time, with a marked reduction in loss of taste/smell as Omicron BA.1 dominated, maintained with BA.2 (44%/45% 17 October 2021, 16%/13% 2 January 2022, 15%/12% 27 March 2022). Cough, fever, shortness of breath, myalgia, fatigue/weakness and headache also decreased after Omicron BA.1 dominated, but sore throat increased, the latter to a greater degree than concurrent increases in PCR-negatives. Fatigue/weakness increased again after BA.2 dominated, although to a similar degree to concurrent increases in PCR-negatives. Symptoms were consistently more common in adults aged 18-65 years than in children or older adults. Conclusions Increases in sore throat (also common in the general community), and a marked reduction in loss of taste/smell, make Omicron harder to detect with symptom-based testing algorithms, with implications for institutional and national testing policies. Summary In a UK community study, loss of taste/smell was markedly less commonly reported with Omicron BA.1/BA.2 than Delta SARS-CoV-2 infections, with smaller declines in reported shortness of breath, myalgia and fatigue/weakness, but increases in sore throat, challenging symptom-based testing algorithms.

Posted ContentDOI
03 Mar 2022
TL;DR: The RECOVERY trial as mentioned in this paper evaluated the use of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, for the treatment of patients admitted to hospital because of COVID-19.
Abstract: SUMMARY Background We evaluated the use of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, for the treatment of patients admitted to hospital because of COVID-19. Methods This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was conducted that included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ). Findings Between 2 February 2021 and 29 December 2021, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% receiving tocilizumab (with planned use within the next 24 hours recorded for a further 9%). Overall, 513 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·98; p=0·026). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of 8 previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths) in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0.57; 95% CI 0.45-0.72). Including the results from RECOVERY into an updated meta-analysis of all 9 completed trials (involving 11,888 randomised patients and 1484 deaths) allocation to baricitinib or other JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0.80; 95% CI 0.71-0.89; p<0.001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no excess of thrombosis, or other safety outcomes. Interpretation In patients hospitalised for COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).