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1.
Virus evolution ; 8(2), 2022.
Article in English | EuropePMC | ID: covidwho-1999627

ABSTRACT

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation. There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

2.
Nature ; 610(7930): 154-160, 2022 10.
Article in English | MEDLINE | ID: covidwho-1991629

ABSTRACT

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , COVID-19/virology , Cities/epidemiology , Contact Tracing , England/epidemiology , Genome, Viral/genetics , Humans , Quarantine/legislation & jurisprudence , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , SARS-CoV-2/isolation & purification , Travel/legislation & jurisprudence
3.
Cell ; 184(20): 5179-5188.e8, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1401294

ABSTRACT

We present evidence for multiple independent origins of recombinant SARS-CoV-2 viruses sampled from late 2020 and early 2021 in the United Kingdom. Their genomes carry single-nucleotide polymorphisms and deletions that are characteristic of the B.1.1.7 variant of concern but lack the full complement of lineage-defining mutations. Instead, the remainder of their genomes share contiguous genetic variation with non-B.1.1.7 viruses circulating in the same geographic area at the same time as the recombinants. In four instances, there was evidence for onward transmission of a recombinant-origin virus, including one transmission cluster of 45 sequenced cases over the course of 2 months. The inferred genomic locations of recombination breakpoints suggest that every community-transmitted recombinant virus inherited its spike region from a B.1.1.7 parental virus, consistent with a transmission advantage for B.1.1.7's set of mutations.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Pandemics , Recombination, Genetic , SARS-CoV-2/genetics , Base Sequence/genetics , COVID-19/virology , Computational Biology/methods , Gene Frequency , Genome, Viral , Genotype , Humans , Mutation , Phylogeny , Polymorphism, Single Nucleotide , United Kingdom/epidemiology , Whole Genome Sequencing/methods
4.
Science ; 373(6557): 889-895, 2021 08 20.
Article in English | MEDLINE | ID: covidwho-1322770

ABSTRACT

Understanding the causes and consequences of the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is crucial to pandemic control yet difficult to achieve because they arise in the context of variable human behavior and immunity. We investigated the spatial invasion dynamics of lineage B.1.1.7 by jointly analyzing UK human mobility, virus genomes, and community-based polymerase chain reaction data. We identified a multistage spatial invasion process in which early B.1.1.7 growth rates were associated with mobility and asymmetric lineage export from a dominant source location, enhancing the effects of B.1.1.7's increased intrinsic transmissibility. We further explored how B.1.1.7 spread was shaped by nonpharmaceutical interventions and spatial variation in previous attack rates. Our findings show that careful accounting of the behavioral and epidemiological context within which variants of concern emerge is necessary to interpret correctly their observed relative growth rates.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2 , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Nucleic Acid Testing , Communicable Disease Control , Genome, Viral , Humans , Incidence , Phylogeography , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spatio-Temporal Analysis , Travel , United Kingdom/epidemiology
5.
Genome Biol ; 22(1): 196, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1295478

ABSTRACT

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


Subject(s)
Cloud Computing , Genomics/organization & administration , SARS-CoV-2/genetics , COVID-19/epidemiology , Epidemiological Monitoring , Genome, Viral , Humans , Sequence Analysis, DNA , United Kingdom , User-Computer Interface , Whole Genome Sequencing
6.
Nature ; 593(7858): 266-269, 2021 05.
Article in English | MEDLINE | ID: covidwho-1152860

ABSTRACT

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show 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. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.


Subject(s)
COVID-19/transmission , COVID-19/virology , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/pathogenicity , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Basic Reproduction Number , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , England/epidemiology , Evolution, Molecular , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/analysis , Spike Glycoprotein, Coronavirus/genetics , Time Factors , Young Adult
7.
Science ; 371(6530): 708-712, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1066806

ABSTRACT

The United Kingdom's COVID-19 epidemic during early 2020 was one of world's largest and was unusually well represented by virus genomic sampling. We determined the fine-scale genetic lineage structure of this epidemic through analysis of 50,887 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes, including 26,181 from the UK sampled throughout the country's first wave of infection. Using large-scale phylogenetic analyses combined with epidemiological and travel data, we quantified the size, spatiotemporal origins, and persistence of genetically distinct UK transmission lineages. Rapid fluctuations in virus importation rates resulted in >1000 lineages; those introduced prior to national lockdown tended to be larger and more dispersed. Lineage importation and regional lineage diversity declined after lockdown, whereas lineage elimination was size-dependent. We discuss the implications of our genetic perspective on transmission dynamics for COVID-19 epidemiology and control.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Genome, Viral , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19/transmission , Chain of Infection , Communicable Disease Control , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/virology , Epidemics , Humans , Phylogeny , Travel , United Kingdom/epidemiology
8.
Cell ; 184(1): 64-75.e11, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-1064909

ABSTRACT

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant.


Subject(s)
Amino Acid Substitution , COVID-19/transmission , COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Aspartic Acid/analysis , Aspartic Acid/genetics , COVID-19/epidemiology , Genome, Viral , Glycine/analysis , Glycine/genetics , Humans , Mutation , SARS-CoV-2/growth & development , United Kingdom/epidemiology , Virulence , Whole Genome Sequencing
9.
Rev Inst Med Trop Sao Paulo ; 62: e30, 2020.
Article in English | MEDLINE | ID: covidwho-246727

ABSTRACT

We conducted the genome sequencing and analysis of the first confirmed COVID-19 infections in Brazil. Rapid sequencing coupled with phylogenetic analyses in the context of travel history corroborate multiple independent importations from Italy and local spread during the initial stage of COVID-19 transmission in Brazil.


Subject(s)
Betacoronavirus/genetics , Communicable Diseases, Imported/transmission , Coronavirus Infections/transmission , Pandemics , Pneumonia, Viral/transmission , Aged , Brazil/epidemiology , COVID-19 , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/virology , Coronavirus Infections/epidemiology , Humans , Middle Aged , Phylogeny , Pneumonia, Viral/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
10.
Cell ; 181(5): 990-996.e5, 2020 05 28.
Article in English | MEDLINE | ID: covidwho-60444

ABSTRACT

The novel coronavirus SARS-CoV-2 was first detected in the Pacific Northwest region of the United States in January 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the United States, we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Travel , Betacoronavirus/isolation & purification , COVID-19 , Connecticut/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Epidemiological Monitoring , Humans , Likelihood Functions , Pandemics , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Travel/legislation & jurisprudence , United States/epidemiology , Washington/epidemiology
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