ORCID Profile
0000-0001-5095-6367
Current Organisations
University of Oxford
,
Oxford University Hospitals NHS Foundation Trust
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Publisher: Elsevier BV
Date: 02-2017
Publisher: Cold Spring Harbor Laboratory
Date: 15-01-2021
DOI: 10.1101/2021.01.12.20249080
Abstract: A new variant of SARS-CoV-2 has emerged which is increasing in frequency, primarily in the South East of England (lineage B.1.1.7 ( 1 ) VUI-202012/01). One potential hypothesis is that infection with the new variant results in higher viral loads, which in turn may make the virus more transmissible. We found higher (sequence derived) viral loads in s les from in iduals infected with the new variant with median inferred viral loads were three-fold higher in in iduals with the new variant. Most of the new variants were s led in Kent and Greater London. We observed higher viral loads in Kent compared to Greater London for both the new variant and other circulating lineages. Outside Greater London, the variant has higher viral loads, whereas within Greater London, the new variant does not have significantly higher viral loads compared to other circulating lineages. Higher variant viral loads outside Greater London could be due to demographic effects, such as a faster variant growth rate compared to other lineages or concentration in particular age-groups. However, our analysis does not exclude a causal link between infection with the new variant and higher viral loads. This is a preliminary analysis and further work is needed to investigate any potential causal link between infection with this new variant and higher viral loads, and whether this results in higher transmissibility, severity of infection, or affects relative rates of symptomatic and asymptomatic infection This is an updated report submitted to NERVTAG in December 2020 as part of urgent investigations into the new variant of SARS-COV-2 (VUI-202012/01). It makes full use of (and is restricted to) all sequence data and associated metadata available to us at the time this original report was submitted and remains provisional. Under normal circumstances more genomes and metadata would be obtained and included before making this report public. We will update this preprint when more genomes and metadata are available and before submitting for peer review.
Publisher: Oxford University Press (OUP)
Date: 11-12-2013
DOI: 10.1093/GBE/EVT204
Publisher: Springer Science and Business Media LLC
Date: 25-03-2021
DOI: 10.1038/S41586-021-03470-X
Abstract: The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England
Publisher: Massachusetts Medical Society
Date: 26-09-2013
Publisher: Springer Science and Business Media LLC
Date: 11-03-2021
DOI: 10.1038/S41586-021-03412-7
Abstract: Transmission of SARS-CoV-2 is uncontrolled in many parts of the world control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant
Publisher: Cold Spring Harbor Laboratory
Date: 22-09-2020
DOI: 10.1101/2020.09.21.307223
Abstract: Clostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000 C. difficile genomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI-III. The emergence of these three novel genomospecies predates clades C1-5 by millions of years, rewriting the global population structure of C. difficile specifically and taxonomy of the Peptostreptococcaceae in general. These genomospecies all show unique and highly ergent toxin gene architecture, advancing our understanding of the evolution of C. difficile and close relatives. Beyond the taxonomic ramifications, this work impacts the diagnosis of CDI worldwide.
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2020
DOI: 10.1101/2020.10.06.328328
Abstract: Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough to inform outbreak response, and cheaply enough to justify dense s ling of even large epidemics. With increased availability of sequencing it is possible for agile networks of sequencing facilities to collaborate on the sequencing and analysis of epidemic genomic data. In response to the ongoing SARS-CoV-2 pandemic in the United Kingdom, the COVID-19 Genomics UK (COG-UK) consortium was formed with the aim of rapidly sequencing 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 Majora, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and s le-associated metadata produced across the COG-UK network. The system was designed and implemented pragmatically to stand up capacity rapidly in a pandemic caused by a novel virus. This approach has underpinned the success of COG-UK, which has rapidly become the leading contributor of SARS-CoV-2 genomes to international databases and has generated over 60,000 sequences to date.
Publisher: Oxford University Press (OUP)
Date: 29-11-2012
Publisher: Springer Science and Business Media LLC
Date: 21-07-2021
DOI: 10.1038/S41564-021-00947-3
Abstract: We report that in a cohort of 45,965 adults, who were receiving either the ChAdOx1 or the BNT162b2 SARS-CoV-2 vaccines, in those who had no prior infection with SARS-CoV-2, seroconversion rates and quantitative antibody levels after a single dose were lower in older in iduals, especially in those aged years. Two vaccine doses achieved high responses across all ages. Antibody levels increased more slowly and to lower levels with a single dose of ChAdOx1 compared with a single dose of BNT162b2, but waned following a single dose of BNT162b2 in older in iduals. In descriptive latent class models, we identified four responder subgroups, including a ‘low responder’ group that more commonly consisted of people aged years, males and in iduals with long-term health conditions. Given our findings, we propose that available vaccines should be prioritized for those not previously infected and that second doses should be prioritized for in iduals aged years. Further data are needed to better understand the extent to which quantitative antibody responses are associated with vaccine-mediated protection.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2021
DOI: 10.1038/S41467-021-26479-2
Abstract: Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection and risk of reinfection, however large-scale representative studies are limited. Here we estimated antibody response after SARS-CoV-2 infection in the general population using representative data from 7,256 United Kingdom COVID-19 infection survey participants who had positive swab SARS-CoV-2 PCR tests from 26-April-2020 to 14-June-2021. A latent class model classified 24% of participants as ‘non-responders’ not developing anti-spike antibodies, who were older, had higher SARS-CoV-2 cycle threshold values during infection (i.e. lower viral burden), and less frequently reported any symptoms. Among those who seroconverted, using Bayesian linear mixed models, the estimated anti-spike IgG peak level was 7.3-fold higher than the level previously associated with 50% protection against reinfection, with higher peak levels in older participants and those of non-white ethnicity. The estimated anti-spike IgG half-life was 184 days, being longer in females and those of white ethnicity. We estimated antibody levels associated with protection against reinfection likely last 1.5-2 years on average, with levels associated with protection from severe infection present for several years. These estimates could inform planning for vaccination booster strategies.
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 12-03-2015
DOI: 10.2807/1560-7917.ES2015.20.10.21059
Abstract: We describe an Australia-wide Clostridium difficile outbreak in 2011 and 2012 involving the previously uncommon ribotype 244. In Western Australia, 14 of 25 cases were community-associated, 11 were detected in patients younger than?65 years, 14 presented to emergency/outpatient departments, and 14 to non-tertiary/community hospitals. Using whole genome sequencing, we confirm ribotype 244 is from the same C. difficile clade as the epidemic ribotype 027. Like ribotype 027, it produces toxins A, B, and binary toxin, however it is fluoroquinolone-susceptible and thousands of single nucleotide variants distinct from ribotype 027. Fifteen outbreak isolates from across Australia were sequenced. Despite their geographic separation, all were genetically highly related without evidence of geographic clustering, consistent with a point source, for ex le affecting the national food chain. Comparison with reference laboratory strains revealed the outbreak clone shared a common ancestor with isolates from the United States and United Kingdom (UK). A strain obtained in the UK was phylogenetically related to our outbreak. Follow-up of that case revealed the patient had recently returned from Australia. Our data demonstrate new C. difficile strains are an on-going threat, with potential for rapid spread. Active surveillance is needed to identify and control emerging lineages.
Publisher: Springer Science and Business Media LLC
Date: 08-02-2022
DOI: 10.1038/S41467-021-27942-W
Abstract: Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2021
Publisher: eLife Sciences Publications, Ltd
Date: 11-06-2021
DOI: 10.7554/ELIFE.64325
Abstract: Clostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000 C. difficile genomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, and pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI–III. The emergence of these three novel genomospecies predates clades C1–5 by millions of years, rewriting the global population structure of C. difficile specifically and taxonomy of the Peptostreptococcaceae in general. These genomospecies all show unique and highly ergent toxin gene architecture, advancing our understanding of the evolution of C. difficile and close relatives. Beyond the taxonomic ramifications, this work may impact the diagnosis of CDI.
Publisher: Cold Spring Harbor Laboratory
Date: 04-01-2021
DOI: 10.1101/2020.12.30.20249034
Abstract: The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic ersity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England extrapolation to other transmission contexts therefore requires caution.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-04-2021
Abstract: A year into the severe acute respiratory syndrome coronavirus 2 pandemic, we are experiencing waves of new variants emerging. Some of these variants have worrying functional implications, such as increased transmissibility or antibody treatment escape. Lythgoe et al. have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within in iduals. Overall, there seem to be consistent and reproducible patterns of within-host virus ersity. The authors observed only one or two variants in most s les, but a few carried many variants. Although the evidence indicates strong purifying selection, including in the spike protein responsible for viral entry, the authors also saw evidence for transmission clusters associated with households and other possible superspreader events. After transmission, most variants fizzled out, but occasionally some initiated ongoing transmission and wider dissemination. Science , this issue p. eabg0821
Publisher: BMJ
Date: 2012
Publisher: Elsevier BV
Date: 02-2022
Publisher: eLife Sciences Publications, Ltd
Date: 15-02-2021
Publisher: Elsevier BV
Date: 04-2017
Publisher: Public Library of Science (PLoS)
Date: 26-12-0001
Publisher: Springer Science and Business Media LLC
Date: 29-06-2022
DOI: 10.1038/S41467-022-31495-X
Abstract: Given high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out in many settings, there is a need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity. We evaluate whether a single vaccination in in iduals who have already been infected with SARS-CoV-2 generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single vaccination with ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults median (50 (IQR: 37–63) years) receiving at least one vaccination, 13,404 (13.3%) had serological/PCR evidence of prior infection. Prior infection significantly boosted antibody responses, producing higher peak levels and/or longer half-lives after one dose of all three vaccines than those without prior infection receiving one or two vaccinations. In those with prior infection, the median time above the positivity threshold was year after the first vaccination. Single-dose vaccination targeted to those previously infected may provide at least as good protection to two-dose vaccination among those without previous infection.
Publisher: Elsevier BV
Date: 2021
Publisher: Microbiology Society
Date: 06-2015
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 10-03-2022
DOI: 10.1038/S41467-022-28898-1
Abstract: The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.
Publisher: Massachusetts Medical Society
Date: 30-12-2021
DOI: 10.1056/NEJMC2103227
Publisher: Public Library of Science (PLoS)
Date: 16-08-2017
Publisher: Cold Spring Harbor Laboratory
Date: 28-05-2020
DOI: 10.1101/2020.05.28.118992
Abstract: Extensive global s ling and whole genome sequencing of the pandemic virus SARS-CoV-2 have enabled researchers to characterise its spread, and to identify mutations that may increase transmission or enable the virus to escape therapies or vaccines. Two important components of viral spread are how frequently variants arise within in iduals, and how likely they are to be transmitted. Here, we characterise the within-host ersity of SARS-CoV-2, and the extent to which genetic ersity is transmitted, by quantifying variant frequencies in 1390 clinical s les from the UK, many from in iduals in known epidemiological clusters. We show that SARS-CoV-2 infections are characterised by low levels of within-host ersity across the entire viral genome, with evidence of strong evolutionary constraint in Spike, a key target of vaccines and antibody-based therapies. Although within-host variants can be observed in multiple in iduals in the same phylogenetic or epidemiological cluster, highly infectious in iduals with high viral load carry only a limited repertoire of viral ersity. Most viral variants are either lost, or occasionally fixed, at the point of transmission, consistent with a narrow transmission bottleneck. These results suggest potential vaccine-escape mutations are likely to be rare in infectious in iduals. Nonetheless, we identified Spike variants present in multiple in iduals that may affect receptor binding or neutralisation by antibodies. Since the fitness advantage of escape mutations in highly-vaccinated populations is likely to be substantial, resulting in rapid spread if and when they do emerge, these findings underline the need for continued vigilance and monitoring.
Publisher: Springer Science and Business Media LLC
Date: 2012
Publisher: Elsevier BV
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 14-02-2022
DOI: 10.1038/S41591-022-01721-6
Abstract: Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 in iduals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older in iduals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Oxford University Press (OUP)
Date: 05-2020
DOI: 10.1093/OFID/OFAA158
Abstract: Whole-genome sequencing clustered Australian Candida auris isolates from sporadic cases within clade III. Case isolates were genomically distinct however, unexpectedly, those from 1 case comprised 2 groups separated by & single nucleotide polymorphisms (SNPs) with no isolate being identical, in contrast to outbreaks where isolates from any 1 in idual have differed by & SNPs. Multidrug resistance was absent. High within-host genetic heterogeneity should be considered when investigating C. auris infections.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Eyre.