Publications
307 results found
Blassel L, Tostevin A, Villabona-Arenas CJ, et al., 2021, Using machine learning and big data to explore the drug resistance landscape in HIV
<jats:title>Abstract</jats:title><jats:p>Drug resistance mutations (DRMs) appear in HIV under treatment pressure. DRMs are commonly transmitted to naive patients. The standard approach to reveal new DRMs is to test for significant frequency differences of mutations between treated and naive patients. However, we then consider each mutation individually and cannot hope to study interactions between several mutations. Here, we aim to leverage the ever-growing quantity of high-quality sequence data and machine learning methods to study such interactions (i.e. epistasis), as well as try to find new DRMs.</jats:p><jats:p>We trained classifiers to discriminate between Reverse Transcriptase Inhibitor (RTI)-experienced and RTI-naive samples on a large HIV-1 reverse transcriptase (RT) sequence dataset from the UK (<jats:italic>n ≈</jats:italic>55, 000), using all observed mutations as binary representation features. To assess the robustness of our findings, our classifiers were evaluated on independent data sets, both from the UK and Africa. Important representation features for each classifier were then extracted as potential DRMs. To find novel DRMs, we repeated this process by removing either features or samples associated to known DRMs.</jats:p><jats:p>When keeping all known resistance signal, we detected sufficiently prevalent known DRMs, thus validating the approach. When removing features corresponding to known DRMs, our classifiers retained some prediction accuracy, and six new mutations significantly associated with resistance were identified. These six mutations have a low genetic barrier, are correlated to known DRMs, and are spatially close to either the RT active site or the regulatory binding pocket. When removing both known DRM features and sequences containing at least one known DRM, our classifiers lose all prediction accuracy. These results likely indicate that all mutations directly conferring res
Abueg M, Hinch R, Wu N, et al., 2021, Modeling the effect of exposure notification and non-pharmaceutical interventions on COVID-19 transmission in Washington state, NPJ DIGITAL MEDICINE, Vol: 4, ISSN: 2398-6352
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- Citations: 42
Colizza V, Grill E, Mikolajczyk R, et al., 2021, Time to evaluate COVID-19 contact-tracing apps, NATURE MEDICINE, Vol: 27, Pages: 361-362, ISSN: 1078-8956
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- Citations: 44
Graham MS, Sudre CH, May A, et al., 2021, Changes in symptomatology, re-infection and transmissibility associated with SARS-CoV-2 variant B.1.1.7: an ecological study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>SARS-CoV-2 variant B.1.1.7 was first identified in December 2020 in England. It is not known if the new variant presents with variation in symptoms or disease course, if previously infected individuals may become reinfected with the new variant, or how the variant’s increased transmissibility affects measures to reduce its spread.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using longitudinal symptom reports from 36,920 users of the COVID Symptom Study app testing positive for Covid-19 between 28 September and 27 December 2020, we performed an ecological study to examine the association between the regional proportion of B.1.1.7 and reported symptoms, disease course, rates of reinfection, and transmissibility.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>We found no evidence for changes in reported symptoms or disease duration associated with B.1.1.7. We found a likely reinfection rate of 0.7% (95% CI 0.6-0.8), but no evidence that this was higher compared to older strains. We found an increase in R(t) by a factor of 1.35 (95% CI 1.02-1.69). Despite this, we found that R(t) fell below 1 during regional and national lockdowns, even in regions with high proportions of B.1.1.7.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The lack of change in symptoms indicates existing testing and surveillance infrastructure do not need to change specifically for the new variant, and the reinfection findings suggest that vaccines are likely to remain effective against the new variant.</jats:p></jats:sec><jats:sec><jats:title>Funding</jats:title><jats:p>Zoe Global Limited, Department of Health, Wellcome Trust, EPSRC, NIHR, MRC, Alzheimer&
Collier DA, De Marco A, Ferreira IATM, et al., 2021, SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies
<jats:title>Abstract</jats:title><jats:p>Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.</jats:p>
Golubchik T, Lythgoe KA, Hall M, et al., 2021, Early analysis of a potential link between viral load and the N501Y mutation in the SARS-COV-2 spike protein
<jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>1</jats:italic>); 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 samples from individuals infected with the new variant with median inferred viral loads were three-fold higher in individuals with the new variant. Most of the new variants were sampled 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</jats:p><jats:sec><jats:title>Document Description and Purpose</jats:title><jats:p>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 subm
Volz E, Hill V, McCrone J, et al., 2021, Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity, Cell, Vol: 184, Pages: 64-75.e11, ISSN: 0092-8674
In February 2020 a substitution at the interface between SARS-CoV-2 Spike protein subunits, Spike D614G, was observed in public databases. The Spike 614G variant subsequently increased in frequency in many locations throughout the world. Global patterns of dispersal of Spike 614G are suggestive of a selective advantage of this variant, however the origin of Spike 614G is associated with early colonization events in Europe and subsequent radiations to the rest of the world. Increasing frequency of 614G may therefore be due to a random founder effect. We investigate the hypothesis for positive selection of Spike 614G at the level of an individual country, the United Kingdom, using more than 25,000 whole genome SARS-CoV-2 sequences collected by COVID-19 Genomics UK Consortium. Using phylogenetic analysis, we identify Spike 614G and 614D clades with unique origins in the UK and from these we extrapolate and compare growth rates of co-circulating transmission clusters. We find that Spike 614G clusters are introduced in the UK later on average than 614D clusters and grow to larger size after adjusting for time of introduction. Phylodynamic analysis does not show a significant increase in growth rates for clusters with the 614G variant, but population genetic modelling indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We also investigate the potential influence of Spike 614D versus G on virulence by matching a subset of records to clinical data on patient outcomes. We do not find any indication that patients infected with the Spike 614G variant have higher COVID-19 mortality, but younger patients have slightly increased odds of 614G carriage. Despite the availability of a very large data set, well represented by both Spike 614 variants, not all approaches showed a conclusive signal of higher transmission rate for 614G, but significant differences in growth, size, and composition of these lineages indicate a need
Mashe T, Takawira FT, Martins LDO, et al., 2021, Genomic epidemiology of the SARS-CoV-2 epidemic in Zimbabwe: Role of international travel and regional migration in spread
<jats:title>Abstract</jats:title><jats:p>Zimbabwe reported its first case of SARS-Cov-2 infection in March 2020, and case numbers increased to more than 8,099 to 16th October 2020. An understanding of the SARS-Cov-2 outbreak in Zimbabwe will assist in the implementation of effective public health interventions to control transmission. Nasopharyngeal samples from 92,299 suspected and confirmed COVID-19 cases reported in Zimbabwe between 20 March and 16 October 2020 were obtained. Available demographic data associated with those cases identified as positive (8,099) were analysed to describe the national breakdown of positive cases over time in more detail (geographical location, sex, age and travel history). The whole genome sequence (WGS) of one hundred SARS-CoV-2-positive samples from the first 120 days of the epidemic in Zimbabwe was determined to identify their relationship to one another and WGS from global samples. Overall, a greater proportion of infections were in males (55.5%) than females (44.85%), although in older age groups more females were affected than males. Most COVID-19 cases (57 %) were in the 20-40 age group. Eight lineages, from at least 25 separate introductions into the region were found using comparative genomics. Of these, 95% had the D614G mutation on the spike protein which was associated with higher transmissibility than the ancestral strain. Early introductions and spread of SARS-CoV-2 were predominantly associated with genomes common in Europe and the United States of America (USA), and few common in Asia at this time. As the pandemic evolved, travel-associated cases from South Africa and other neighbouring countries were also recorded. Transmission within quarantine centres occurred when travelling nationals returning to Zimbabwe. International and regional migration followed by local transmission were identified as accounting for the development of the SARS-CoV-2 epidemic in Zimbabwe. Based on this, rapid implementati
Zhang Y, Wymant C, Laeyendecker O, et al., 2021, Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: 30-37, ISSN: 1058-4838
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- Citations: 9
Davies NG, Abbott S, Barnard RC, et al., 2020, Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England
<jats:p>A novel SARS-CoV-2 variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in November 2020 and is rapidly spreading towards fixation. Using a variety of statistical and dynamic modelling approaches, we estimate that this variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine roll-out, COVID-19 hospitalisations and deaths across England in 2021 will exceed those in 2020. Concerningly, VOC 202012/01 has spread globally and exhibits a similar transmission increase (59–74%) in Denmark, Switzerland, and the United States.</jats:p>
Fogel JM, Bonsall D, Cummings V, et al., 2020, Performance of a high-throughput next-generation sequencing method for analysis of HIV drug resistance and viral load, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 75, Pages: 3510-3516, ISSN: 0305-7453
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- Citations: 6
Kendall M, Milsom L, Abeler-Dorner L, et al., 2020, Epidemiological changes on the Isle of Wight after the launch of the NHS Test and Trace programme: a preliminary analysis, LANCET DIGITAL HEALTH, Vol: 2, Pages: E658-E666
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- Citations: 43
Novitsky V, Zahralban-Steele M, Moyo S, et al., 2020, Mapping of HIV-1C transmission networks reveals extensive spread of viral lineages across villages in Botswana treatment-as-prevention trial, Journal of Infectious Diseases, Vol: 222, Pages: 1670-1680, ISSN: 0022-1899
BackgroundPhylogenetic mapping of HIV-1 lineages circulating across defined geographical locations is promising for better understanding HIV transmission networks to design optimal prevention interventions.MethodsWe obtained near full-length HIV-1 genome sequences from people living with HIV (PLWH), including participants on antiretroviral treatment in the Botswana Combination Prevention Project, conducted in 30 Botswana communities in 2013–2018. Phylogenetic relationships among viral sequences were estimated by maximum likelihood.ResultsWe obtained 6078 near full-length HIV-1C genome sequences from 6075 PLWH. We identified 984 phylogenetically distinct HIV-1 lineages (molecular HIV clusters) circulating in Botswana by mid-2018, with 2–27 members per cluster. Of these, dyads accounted for 62%, approximately 32% (n = 316) were found in single communities, and 68% (n = 668) were spread across multiple communities. Men in clusters were approximately 3 years older than women (median age 42 years, vs 39 years; P < .0001). In 65% of clusters, men were older than women, while in 35% of clusters women were older than men. The majority of identified viral lineages were spread across multiple communities.ConclusionsA large number of circulating phylogenetically distinct HIV-1C lineages (molecular HIV clusters) suggests highly diversified HIV transmission networks across Botswana communities by 2018.
Thomson EC, Rosen LE, Shepherd JG, et al., 2020, The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity
<jats:p>SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and <jats:italic>in vitro</jats:italic> replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.</jats:p>
Pritchard MG, 2020, COVID-19 symptoms at hospital admission vary with age and sex: ISARIC multinational study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>International, prospective observational study of 60⍰109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30-to 60-year-olds (respectively 80%, 79%, 69%; at least one 95%). They were reported less frequently in children (≤18 years: 69%, 48%, 23%; 85%), older adults (≥70 years: 61%, 62%, 65%; 90%), and women (66%, 66%, 64%; 90%; vs men 71%, 70%, 67%; 93%). The most common atypical presentation under 60 years of age was nausea and vomiting, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.
Lehtinen S, Croucher NJ, Blanquart F, et al., 2020, Epidemiological dynamics of bacteriocin competition and antibiotic resistance
<jats:title>Abstract</jats:title><jats:p>Bacteriocins, toxic peptides involved in the competition between bacterial strains, are extremely diverse. Previous work on bacteriocin dynamics has highlighted the role of non-transitive ‘rock-paper-scissors’ competition in maintaining the coexistence of different bacteriocin profiles. The focus to date has primarily been on bacteriocin interactions at the within-host scale. Yet, in species such as <jats:italic>Streptococcus pneumoniae</jats:italic> with relatively short periods of colonisation and limited within-host diversity, ecological outcomes are also shaped by processes at the epidemiological (between-host) scale. Here, we first investigate bacteriocin dynamics and diversity in epidemiological models. We find that in these models, bacteriocin diversity is more readily maintained than in within-host models, and with more possible combinations of coexisting bacteriocin profiles. Indeed, maintenance of diversity in epidemiological models does not require rock-paper-scissors dynamics; it can also occur through a competition-colonisation trade-off. Second, we investigate the link between bacteriocin diversity and diversity at antibiotic resistance loci. Previous work has proposed that bacterial duration of colonisation modulates the fitness of antibiotic resistance. Due to their inhibitory effects, bacteriocins are a plausible candidate for playing a role in the duration of colonisation episodes. We extend the epidemiological model of bacteriocin dynamics to incorporate an antibiotic resistance locus and demonstrate that bacteriocin diversity can indeed maintain the coexistence of antibiotic sensitive and resistant strains.</jats:p>
Nicholls SM, Poplawski R, Bull MJ, et al., 2020, MAJORA: Continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance
<jats:title>Abstract</jats:title><jats:p>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 sampling 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.</jats:p><jats:p>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.</jats:p><jats:p>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 sample-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.</jats:p>
Azarian T, Martinez PP, Arnold BJ, et al., 2020, Frequency-dependent selection can forecast evolution in <i>Streptococcus pneumoniae</i>, PLOS BIOLOGY, Vol: 18, ISSN: 1544-9173
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- Citations: 9
Hinch R, Probert WJM, Nurtay A, et al., 2020, OpenABM-Covid19 - an agent-based model for non-pharmaceutical interventions against COVID-19 including contact tracing
<jats:title>Abstract</jats:title><jats:p>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 models being used to predict the spread of infection and assess the impact of public health measures. Here, we present OpenABM-Covid19: an agent-based simulation of the epidemic including detailed age-stratification and realistic social networks. By default the model is parameterised to UK demographics and calibrated to the UK epidemic, however, it can easily be re-parameterised for other countries. OpenABM-Covid19 can evaluate non-pharmaceutical interventions, including both manual and digital contact tracing. It can simulate a population of 1 million people in seconds per day allowing parameter sweeps and formal statistical model-based inference. The code is open-source and has been developed by teams both inside and outside academia, with an emphasis on formal testing, documentation, modularity and transparency. A key feature of OpenABM-Covid19 is its Python interface, which has allowed scientists and policymakers to simulate dynamic packages of interventions and help compare options to suppress the COVID-19 epidemic.</jats:p>
Bonsall D, Golubchik T, de Cesare M, et al., 2020, A comprehensive genomics solution for HIV surveillance and clinical monitoring in low-income settings, Journal of Clinical Microbiology, Vol: 58, Pages: 1-13, ISSN: 0095-1137
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 generalized HIV epidemics in low- and middle-income countries. Here, we present veSEQ-HIV, a high-throughput, cost-effective NGS sequencing method and computational pipeline tailored specifically to HIV, which can be performed using leftover blood drawn for routine CD4 cell count testing. This method overcomes several major technical challenges that have prevented HIV sequencing from being used routinely in public health efforts; it is fast, robust, and cost-efficient, and generates full genomic sequences of diverse strains of HIV without bias. The complete veSEQ-HIV pipeline provides viral load estimates and quantitative summaries of drug resistance mutations; it also exploits information on within-host viral diversity to construct directed transmission networks. We evaluated the method’s performance using 1,620 plasma samples collected from individuals attending 10 large urban clinics in Zambia as part of the HPTN 071-2 study (PopART Phylogenetics). Whole HIV genomes were recovered from 91% of samples with a viral load of >1,000 copies/ml. The cost of the assay (30 GBP per sample) compares favorably with existing VL and HIV genotyping tests, proving an affordable option for combining HIV clinical monitoring with molecular epidemiology and drug resistance surveillance in low-income settings.
Ferretti L, Ledda A, Wymant C, et al., 2020, The timing of COVID-19 transmission
<jats:title>Abstract</jats:title><jats:p>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 symptomatic individuals, the timing of transmission of SARS-CoV-2 is more strongly linked to the onset of clinical symptoms of COVID-19 than to the time since infection. We found that it was approximately centered and symmetric around the onset of symptoms, with three quarters of events occurring in the window from 2-3 days before to 2-3 days after. However, we caution against overinterpretation of the right tail of the distribution, due to its dependence on behavioural factors and interventions. We also found that the pre-symptomatic infectious period extended further back in time for individuals with longer incubation periods. This strongly suggests that information about when a case was infected should be collected where possible, in order to assess how far into the past their contacts should be traced. Overall, the fraction of transmission from strictly pre-symptomatic infections was high (41%; 95%CI 31-50%), which limits the efficacy of symptom-based interventions, and the large fraction of transmissions (35%; 95%CI 26-45%) that occur on the same day or the day after onset of symptoms underlines the critical importance of individuals distancing themselves from others as soon as they notice any symptoms, even if they are mild. Rapid or at-home testing and contextual risk information would greatly facilitate efficient early isolation.</jats:p>
Abueg M, Hinch R, Wu N, et al., 2020, Modeling the combined effect of digital exposure notification and non-pharmaceutical interventions on the COVID-19 epidemic in Washington state
<jats:title>Abstract</jats:title><jats:p>Contact tracing is increasingly being used to combat COVID-19, and digital implementations are now being deployed, many of them based on Apple and Google’s Exposure Notification System. These systems are new and are based on smartphone technology that has not traditionally been used for this purpose, presenting challenges in understanding possible outcomes. In this work, we use individual-based computational models to explore how digital exposure notifications can be used in conjunction with non-pharmaceutical interventions, such as traditional contact tracing and social distancing, to influence COVID-19 disease spread in a population. Specifically, we use a representative model of the household and occupational structure of three counties in the state of Washington together with a proposed digital exposure notifications deployment to quantify impacts under a range of scenarios of adoption, compliance, and mobility. In a model in which 15% of the population participated, we found that digital exposure notification systems could reduce infections and deaths by approximately 8% and 6%, effectively complementing traditional contact tracing. We believe this can serve as guidance to health authorities in Washington state and beyond on how exposure notification systems can complement traditional public health interventions to suppress the spread of COVID-19.</jats:p>
Pickles M, Cori A, Probert W, et al., 2020, PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial
<jats:title>Abstract</jats:title><jats:p>Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention.</jats:p>
Kendall M, Milsom L, Abeler-Dörner L, et al., 2020, COVID-19 incidence and R decreased on the Isle of Wight after the launch of the Test, Trace, Isolate programme
<jats:title>Abstract</jats:title><jats:p>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 Local Authorities in England, and at the National level, before and after the launch of the programme on the Isle of Wight. We used Bayesian and Maximum-Likelihood methods to estimate R, and compared the Isle of Wight to other areas using a synthetic control method. We observed significant decreases in incidence and R on the Isle of Wight immediately after the launch. These results are robust across each of our approaches. Our results show that the sub-epidemic on the Isle of Wight was controlled significantly more effectively than the sub-epidemics of most other Upper Tier Local Authorities, changing from having the third highest reproduction number R (of 150) before the intervention to the tenth lowest afterwards. The data is not yet available to establish a causal link. However, the findings highlight the need for further research to determine the causes of this reduction, as these might translate into local and national non-pharmaceutical intervention strategies in the period before a treatment or vaccination becomes available.</jats:p>
Aanensen DM, Abudahab K, Adams A, et al., 2020, An integrated national scale SARS-CoV-2 genomic surveillance network, The Lancet Microbe, Vol: 1, Pages: E99-E100, ISSN: 2666-5247
Parker MJ, Fraser C, Abeler-Dorner L, et al., 2020, Ethics of instantaneous contact tracing using mobile phone apps in the control of the COVID-19 pandemic, JOURNAL OF MEDICAL ETHICS, Vol: 46, Pages: 427-431, ISSN: 0306-6800
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- Citations: 122
El Bouzidi K, Kemp SA, Datir RP, et al., 2020, High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 75, Pages: 1575-1579, ISSN: 0305-7453
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- Citations: 15
Lythgoe KA, Hall M, Ferretti L, et al., 2020, Within-host genomics of SARS-CoV-2
<jats:title>Abstract</jats:title><jats:p>Extensive global sampling 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 individuals, and how likely they are to be transmitted. Here, we characterise the within-host diversity of SARS-CoV-2, and the extent to which genetic diversity is transmitted, by quantifying variant frequencies in 1390 clinical samples from the UK, many from individuals in known epidemiological clusters. We show that SARS-CoV-2 infections are characterised by low levels of within-host diversity 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 individuals in the same phylogenetic or epidemiological cluster, highly infectious individuals with high viral load carry only a limited repertoire of viral diversity. 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 individuals. Nonetheless, we identified Spike variants present in multiple individuals 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.</jats:p>
Ferretti L, Wymant C, Kendall M, et al., 2020, Quantifying SARS-CoV-2 transmission suggests epidemic control with digital contact tracing, SCIENCE, Vol: 368, Pages: 619-+, ISSN: 0036-8075
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- Citations: 1431
Stirrup OT, Asboe D, Pozniak A, et al., 2020, Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation, HIV Medicine, Vol: 21, Pages: 309-321, ISSN: 1464-2662
OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.
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