ORCID Profile
0000-0002-6072-5949
Current Organisation
University of Cambridge
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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: eLife Sciences Publications, Ltd
Date: 02-03-2021
DOI: 10.7554/ELIFE.64618
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.
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: Elsevier BV
Date: 11-2021
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: eLife Sciences Publications, Ltd
Date: 13-08-2021
DOI: 10.7554/ELIFE.66857
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 ersity could theoretically help identify close contacts. Here we describe the patterns of within-host ersity in 1181 SARS-CoV-2 s les sequenced to high depth in duplicate. 95.1% of s les 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 ersity 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 s les result from infection by a single lineage, we identify multiple putative ex les of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between s les could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.
Publisher: European Centre for Disease Control and Prevention (ECDC)
Date: 13-08-2020
DOI: 10.2807/1560-7917.ES.2020.25.32.2001410
Abstract: We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.
Publisher: Cold Spring Harbor Laboratory
Date: 25-12-2020
DOI: 10.1101/2020.12.23.424229
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 ersity could theoretically help identify close contacts. Here we describe the patterns of within-host ersity in 1,181 SARS-CoV-2 s les sequenced to high depth in duplicate. 95% of s les 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 ersity 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 s les result from infection by a single lineage, we identify multiple putative ex les of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between s les could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.
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: 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: Elsevier BV
Date: 2021
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: Springer Science and Business Media LLC
Date: 27-12-0001
DOI: 10.1038/S41586-021-04069-Y
Abstract: The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of s led SARS-CoV-2 genomes on 26 June 2021.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Malte Pinckert.