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1.
Nat Commun ; 13(1): 460, 2022 01 24.
Article in English | MEDLINE | ID: covidwho-1651070

ABSTRACT

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.


Subject(s)
COVID-19/transmission , Contact Tracing/methods , Disease Outbreaks/prevention & control , SARS-CoV-2/isolation & purification , Animals , COVID-19/epidemiology , COVID-19/virology , Chlorocebus aethiops , Humans , RNA-Seq/methods , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Time Factors , Vero Cells , Viral Load/genetics , Viral Load/physiology , Virus Replication/genetics , Virus Replication/physiology , Virus Shedding/genetics , Virus Shedding/physiology
2.
Nat Commun ; 12(1): 5730, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1447303

ABSTRACT

Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.


Subject(s)
COVID-19/transmission , Immune Evasion/genetics , Models, Biological , Pandemics/statistics & numerical data , SARS-CoV-2/pathogenicity , Adolescent , Adult , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Computer Simulation , Forecasting/methods , Humans , Middle Aged , Mutation , Pandemics/prevention & control , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Stochastic Processes , United Kingdom/epidemiology , Vaccination/statistics & numerical data , Young Adult
3.
Philos Trans R Soc Lond B Biol Sci ; 376(1829): 20200264, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1309684

ABSTRACT

Early assessments of the growth rate of COVID-19 were subject to significant uncertainty, as expected with limited data and difficulties in case ascertainment, but as cases were recorded in multiple countries, more robust inferences could be made. Using multiple countries, data streams and methods, we estimated that, when unconstrained, European COVID-19 confirmed cases doubled on average every 3 days (range 2.2-4.3 days) and Italian hospital and intensive care unit admissions every 2-3 days; values that are significantly lower than the 5-7 days dominating the early published literature. Furthermore, we showed that the impact of physical distancing interventions was typically not seen until at least 9 days after implementation, during which time confirmed cases could grow eightfold. We argue that such temporal patterns are more critical than precise estimates of the time-insensitive basic reproduction number R0 for initiating interventions, and that the combination of fast growth and long detection delays explains the struggle in countries' outbreak response better than large values of R0 alone. One year on from first reporting these results, reproduction numbers continue to dominate the media and public discourse, but robust estimates of unconstrained growth remain essential for planning worst-case scenarios, and detection delays are still key in informing the relaxation and re-implementation of interventions. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.


Subject(s)
COVID-19/epidemiology , Models, Theoretical , Pandemics , COVID-19/virology , Humans , Italy/epidemiology , Physical Distancing , SARS-CoV-2
4.
Science ; 372(6539)2021 04 16.
Article in English | MEDLINE | ID: covidwho-1125076

ABSTRACT

Extensive global sampling and sequencing of the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have enabled researchers to monitor its spread and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals and how likely they are to be transmitted. To characterize within-host diversity and transmission, we deep-sequenced 1313 clinical samples from the United Kingdom. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high and by a narrow bottleneck at transmission. Most variants are either lost or occasionally fixed at the point of transmission, with minimal persistence of shared diversity, patterns that are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape SARS-CoV-2 variants are likely to arise infrequently but could spread rapidly if successfully transmitted.


Subject(s)
COVID-19/transmission , COVID-19/virology , Genetic Variation , SARS-CoV-2/genetics , COVID-19/immunology , Coinfection/virology , Coronavirus Infections/virology , Coronavirus OC43, Human , Family Characteristics , Genome, Viral , Humans , Immune Evasion , Mutation , Phylogeny , RNA, Viral/genetics , RNA-Seq , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Selection, Genetic , Spike Glycoprotein, Coronavirus/genetics , United Kingdom , Viral Load
5.
Nature ; 584(7820):192-192, 2020.
Article | WHO COVID | ID: covidwho-734237

ABSTRACT

Letter to the Editor

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