Chris Wymant's research while affiliated with University of Oxford and other places

Publications (52)

Article
The SARS-CoV-2 epidemic has been extended by the evolution of more transmissible viral variants. In autumn 2020, the B.1.177 lineage became the dominant variant in England, before being replaced by the B.1.1.7 (Alpha) lineage in late 2020, with the sweep occurring at different times in each region. This period coincided with a large number of non-p...
Article
Full-text available
The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and the agent-based model Covasim, in June 2021, to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50–80% more transmissible than B.1.177 and...
Preprint
Full-text available
Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining duration of infection classify samples into recent and non-recent and are unable to give more granular TSI estimates. These binary classifications have a limited recency time window of several...
Article
Full-text available
Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 104 and 105 copies of viral RNA per ml. Here we aimed to detect tran...
Article
We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advan...
Preprint
Full-text available
The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and calibration of an stochastic agent-based model Covasim to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B....
Preprint
Full-text available
Quarantining close contacts of individuals infected with SARS-CoV-2 for 10 to 14 days is a key strategy in reducing transmission. However, quarantine requirements are often unpopular, with low adherence, especially when a large fraction of the population has been vaccinated. Daily contact testing (DCT), in which contacts are required to isolate onl...
Article
Full-text available
SARS-CoV-2 has spread across the world, causing high mortality and unprecedented restrictions on social and economic activity. Policymakers are assessing how best to navigate through the ongoing epidemic, with computational models being used to predict the spread of infection and assess the impact of public health measures. Here, we present OpenABM...
Article
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The COVID-19 pandemic has seen digital contact tracing emerge around the world to help prevent spread of the disease. A mobile phone app records proximity events between app users, and when a user tests positive for COVID-19, their recent contacts can be notified instantly. Theoretical evidence has supported this new public health intervention1–6,...
Preprint
Full-text available
Digital contact tracing is a public health intervention. It should be integrated with local health policy, provide rapid and accurate notifications to exposed individuals, and encourage high app uptake and adherence to quarantine. Real-time monitoring and evaluation of effectiveness of app-based contact tracing is key for improvement and public tru...
Article
Full-text available
Background In May 2020, the UK National Health Service (NHS) Test and Trace programme was launched in England in response to the COVID-19 pandemic. The programme was first rolled out on the Isle of Wight and included version 1 of the NHS contact tracing app. The aim of the study was to make a preliminary assessment of the epidemiological impact of...
Preprint
The timing of SARS-CoV-2 transmission is a critical factor to understand the epidemic trajectory and the impact of isolation, contact tracing and other non- pharmaceutical interventions on the spread of COVID-19 epidemics. We examined the distribution of transmission events with respect to exposure and onset of symptoms. We show that for symptomati...
Article
Full-text available
Viral genetic sequencing can be used to monitor the spread of HIV drug resistance, identify appropriate antiretroviral regimes, and characterize transmission dynamics. Despite decreasing costs, next-generation sequencing (NGS) is still prohibitively costly for routine use in generalised HIV epidemics in low- and middle-income countries. Here, we pr...
Preprint
Full-text available
In May 2020 the UK introduced a Test, Trace, Isolate programme in response to the COVID-19 pandemic. The programme was first rolled out on the Isle of Wight and included Version 1 of the NHS contact tracing app. We used COVID-19 daily case data to infer incidence of new infections and estimate the reproduction number R for each of 150 Upper Tier Lo...
Article
Full-text available
Instantaneous contact tracing New analyses indicate that severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is more infectious and less virulent than the earlier SARS-CoV-1, which emerged in China in 2002. Unfortunately, the current virus has greater epidemic potential because it is difficult to trace mild or presymptomatic infections. As...
Preprint
Mobile phone apps implementing algorithmic contact tracing can speed up the process of tracing newly diagnosed individuals, spreading information instantaneously back through a past contact network to inform them that they are at risk of being infected, and thus allow them to take appropriate social distancing and testing measures. The aim of non-p...
Article
Full-text available
Background: International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. Methods:...
Article
Full-text available
BACKGROUND: International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda. METHODS: W...
Article
Background: Phylogenetic analysis can be used to assess HIV transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Methods: Complete next generation sequencing (NGS) data were obtained for 105 unique index-partner sampl...
Article
Full-text available
To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these ‘source’ populations are. Here we demonstrate how viral deep-sequencing can be used to rec...
Article
Full-text available
Understanding which HIV-1 variants are most likely to be transmitted is important for vaccine design and predicting virus evolution. Since most infections are founded by single variants, it has been suggested that selection at transmission has a key role in governing which variants are transmitted. We show that the composition of the viral populati...
Article
Scientific institutions invariably have policies for preventing and reducing harm, which address problems such as physical safety and data security. Surely the protection of planetary health, through the dramatic carbon cuts that are now urgently required, has a place in institutional policy, too.
Preprint
Full-text available
Understanding which HIV-1 variants are most likely to be transmitted is important for vaccine design and predicting virus evolution. Since most infections are founded by single variants, it has been suggested that selection at transmission has a key role in governing which variants are transmitted. We show that the composition of the viral populati...
Preprint
Full-text available
High-throughput viral genetic sequencing is needed to monitor the spread of drug resistance, direct optimal antiretroviral regimes, and to identify transmission dynamics in generalised HIV epidemics. Public health efforts to sequence HIV genomes at scale face three major technical challenges: (i) minimising assay cost and protocol complexity, (ii)...
Article
Full-text available
Studying the evolution of viruses and their molecular epidemiology relies on accurate viral sequence data, so that small differences between similar viruses can be meaningfully interpreted. Despite its higher throughput and more detailed minority variant data, next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accura...
Article
Full-text available
For the production of viral genomic RNA, HIV-1 is dependent on an early viral protein, Tat, which is required for high-level transcription. The quantity of viral RNA detectable in blood of HIV-1 infected individuals varies dramatically, and a factor involved could be the efficiency of Tat protein variants to stimulate RNA transcription. HIV-1 virul...
Chapter
We describe a detailed protocol for the manual workup of blood (plasma/serum) samples from individuals infected with the human immunodeficiency virus type 1 (HIV-1) for deep sequence analysis of the viral genome. The study optimizing the assay was performed in the context of the BEEHIVE (Bridging the Evolution and Epidemiology of HIV in Europe) pro...
Article
Full-text available
A central feature of pathogen genomics is that different infectious particles (virions, bacterial cells, etc.) within an infected individual may be genetically distinct, with patterns of relatedness amongst infectious particles being the result of both within-host evolution and transmission from one host to the next. Here we present a new software...
Preprint
Full-text available
A central feature of pathogen genomics is that different infectious particles (virions, bacterial cells, etc.) within an infected individual may be genetically distinct, with patterns of relatedness amongst infectious particles being the result of both within-host evolution and transmission from one host to the next. Here we present a new software...
Article
Full-text available
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the “Phylogenetics and Networks for Generalised HIV Epidemics in Africa” consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai...
Data
Schematic of a donor-recipient pair. On the left, the genealogy of a donor transmitting to a recipient. Arrows denote the time of sampling and measurement of each partner. We assume the donor is measured and sampled before the branching in the genealogy (which may be anterior to the transmission event because of within-host diversity). On the right...
Article
Full-text available
HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, whic...
Data
Maximum likelihood subtype B phylogeny. The maximum likelihood phylogeny of viral sequences of subtype B used for the estimation of heritability (N = 1581), with edges coloured by viral load value (in log10 copies/mL). Black points show nodes with bootstrap values greater than 90%. The data used in the figure is provided as supplementary informatio...
Data
Analysis of heritability for another viral load measure, for a linear model with country included as a covariate, and for other inclusion criteria for viral sequences. (DOCX)
Data
Linkage disequilibrium in the population as a function of the distance separating pairs of loci. We considered all subtype B sequences (N = 1581), and calculated the linkage disequilibrium for 100,000 pairs of positions where the two most common nucleotides have frequency greater than 0.01. Linkage disequilibrium was calculated as D = (XAB-pA pB)/√...
Data
Estimated heritability as a function of sample size. Estimated heritability under the BM (top panel) and OU (bottom panel) models, as a function of sample size. We randomly sampled 40 subsets of the full dataset (subtype B only, N = 1581) and inferred maximum likelihood parameters and heritability in each subset. Bullets show the maximum likelihood...
Data
Increase in phenotypic variance in the data and predicted increase in genetic variance in the phylogenetic models. Bullets show the variance in GSVL (black) and SPVL (gray) among subtype B samples as a function of the time of the sample, calculated over 2-years intervals. The corresponding lines show the linear regression, with a significant increa...
Data
Analysis of temporal trends in GSVL and SPVL. (DOCX)
Data
The relationship between phylogenetic heritability and donor-recipient regression. (DOCX)
Data
Analysis of heritability stratified by country, gender, mode of transmission. (DOCX)
Data
Analysis of variance for three viral load measures, for the subset of patients infected by subtype B virus. (DOCX)
Data
Analysis of variance for GSVL and SPVL viral load measures, for patients infected by all subtypes (N = 2028). (DOCX)
Article
Full-text available
To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai...
Preprint
Full-text available
Next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of rapid between- and within-host evolution may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to b...

Citations

... Furthermore, in some cases, extremely low values for their specificity were reported [8,9,10], suggesting that false positives may be common, J o u r n a l P r e -p r o o f Journal Pre-proof although this later appeared not to be the case for the devices that were systematically tested and rolled out to the wider public in the UK [1,11]. Models of SARS-CoV-2 testing and observational studies predicted that regular asymptomatic testing and contact-tracing could significantly reduce transmission rates in the population [12,13,14,15]. Furthermore, specific studies on hospitals [16], care-homes [17], and schools [18,19] have demonstrated the impact that regular LFD testing can have and has had on reducing transmission in these vital settings. ...
... Subsequently, the combined availability of licensed vaccines, new therapeutic opportunities and non-pharmaceutical interventions drastically reduced the mortality. The continuous SARS-CoV-2 evolution with appearance of new VOCs (Beta, Gamma, Delta and Omicron) raises important concerns about the effectiveness of the current vaccination strategies [9][10][11]. ...
... Those problems delay every prediction whatever the domain and authorities are eager to control the spread of coronavirus. Numerous studies [20][21][22] emphasized the use of mathematics to understand the spread of COVID-19 and the results of vaccinations. From a number of works [23][24][25][26], authors found that the pandemic tendency will be unstable (decreasing and increasing as well within years). ...
... There were 650,000 people that died of AIDS related causes in the year 2021 alone which amounts to one death every minute (https://aidsinfo.unaids.org/). The recent recognition of a more pathogenic variant of HIV-1 circulating in the Netherlands places increased pressure on the need for an effective prophylactic vaccine [2]. Prior to the COVID-19 pandemic, the availability of healthcare and multiple antiretroviral drugs for many in developed countries significantly reduced HIV transmission, viral loads, and disease progression, resulting in an extension of life for many HIV infected persons. ...
... The local time-varying reproduction number is an important quantity to monitor the infectiousness and transmissibility of diseases and, therefore, to design and adjust public health responses during an outbreak. Recent examples include monitoring transmission of the COVID-19 pandemic and demonstrating the efficacy of non-pharmaceutical interventions in more than 100 countries [1][2][3][4][5][6]. The value of the local time-varying reproduction number, R local * (t), represents the expected number of secondary local cases arising from a primary case infected at time t. ...
... On the basis of the above research, the researchers pushed the agent-based model from theory to application, and formed a series of agent-based model open source simulation platforms represented by covasim [44] and openABM-covid19 [45] . These open-source platforms focus on multiple scenarios. ...
... Sachs et al. [2] reported similar findings while introducing a mobile health tool during the 2014-16 Ebola epidemic in West Africa. There are recent studies on the effectiveness of DCT apps in real-world settings in La Gomera, Spain [11], Switzerland [12], Norway [13] and the UK [14] that conclude positively about the performance of the app. The results are difficult to compare with our findings because the effectiveness was estimated via indirect parameters due to the decentralized approach of the apps. ...
... The maximum of global daily new cases have exceeded 1,000,000, and situations in many countries are increasingly aggravating. It is pressing to find efficient ways to suppress the transmission of SARS-CoV-2 [2][3][4][5][6][7][8][9][10][11] , which has been recognized as top priority since the very beginning of the initial outbreak in China and reiterated by the multidisciplinary online conference on 3 August 2020, organized by the World Health Organization 12 . ...
... During the time period of a wave, usually the first half presented an increasing trend and was followed by a decreasing trend in the second half. The incubation period of COVID-19 was around 8.2 to 15.6 days (approximately 1 to 2 weeks) [37] with an infectious period of around 2-3 days before and after the onset of symptoms [38]. In other words, 2 months indicates half of a wave, which is about 4 to 8 rounds of infections. ...
... The collection of reliable data in these environments (e.g., schools, summer camps) is itself a nontrivial task. During the pandemic, several local and national governments have launched smartphone digital contact tracing (DCT) apps based on the Bluetooth Low Energy (BLE) technology [26] and the GAEN (Google and Apple Exposure Notification) interface [27], and several studies have shown the effectiveness of Bluetooth-based DCT using real-world contact patterns [28,29] and in pilot and country-wide studies conducted in Switzerland, the United Kingdom (the Isle of Wight and the whole country), and Spain (Gomera island) [30][31][32][33]. ...