Publications
307 results found
Ghafari M, Hall M, Golubchik T, et al., 2024, Prevalence of persistent SARS-CoV-2 in a large community surveillance study., Nature, Vol: 626, Pages: 1094-1101
Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.
Ferretti L, Wymant C, Petrie J, et al., 2024, Digital measurement of SARS-CoV-2 transmission risk from 7 million contacts., Nature, Vol: 626, Pages: 145-150
How likely is it to become infected by SARS-CoV-2 after being exposed? Almost everyone wondered about this question during the COVID-19 pandemic. Contact-tracing apps1,2 recorded measurements of proximity3 and duration between nearby smartphones. Contacts-individuals exposed to confirmed cases-were notified according to public health policies such as the 2 m, 15 min guideline4,5, despite limited evidence supporting this threshold. Here we analysed 7 million contacts notified by the National Health Service COVID-19 app6,7 in England and Wales to infer how app measurements translated to actual transmissions. Empirical metrics and statistical modelling showed a strong relation between app-computed risk scores and actual transmission probability. Longer exposures at greater distances had risk similar to that of shorter exposures at closer distances. The probability of transmission confirmed by a reported positive test increased initially linearly with duration of exposure (1.1% per hour) and continued increasing over several days. Whereas most exposures were short (median 0.7 h, interquartile range 0.4-1.6), transmissions typically resulted from exposures lasting between 1 h and several days (median 6 h, interquartile range 1.4-28). Households accounted for about 6% of contacts but 40% of transmissions. With sufficient preparation, privacy-preserving yet precise analyses of risk that would inform public health measures, based on digital contact tracing, could be performed within weeks of the emergence of a new pathogen.
Monod M, Brizzi A, Galiwango RM, et al., 2024, Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda, Nature Microbiology, Vol: 9, Pages: 35-54, ISSN: 2058-5276
HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15-24 years) from older men declined by about one-third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men's health in Africa.
Hall M, Golubchik T, Bonsall D, et al., 2024, Demographics of sources of HIV-1 transmission in Zambia: a molecular epidemiology analysis in the HPTN 071 PopART study, The Lancet Microbe, Vol: 5, Pages: E62-E71, ISSN: 2666-5247
BACKGROUND: In the last decade, universally available antiretroviral therapy (ART) has led to greatly improved health and survival of people living with HIV in sub-Saharan Africa, but new infections continue to appear. The design of effective prevention strategies requires the demographic characterisation of individuals acting as sources of infection, which is the aim of this study. METHODS: Between 2014 and 2018, the HPTN 071 PopART study was conducted to quantify the public health benefits of ART. Viral samples from 7124 study participants in Zambia were deep-sequenced as part of HPTN 071-02 PopART Phylogenetics, an ancillary study. We used these sequences to identify likely transmission pairs. After demographic weighting of the recipients in these pairs to match the overall HIV-positive population, we analysed the demographic characteristics of the sources to better understand transmission in the general population. FINDINGS: We identified a total of 300 likely transmission pairs. 178 (59·4%) were male to female, with 130 (95% CI 110-150; 43·3%) from males aged 25-40 years. Overall, men transmitted 2·09-fold (2·06-2·29) more infections per capita than women, a ratio peaking at 5·87 (2·78-15·8) in the 35-39 years source age group. 40 (26-57; 13·2%) transmissions linked individuals from different communities in the trial. Of 288 sources with recorded information on drug resistance mutations, 52 (38-69; 18·1%) carried viruses resistant to first-line ART. INTERPRETATION: HIV-1 transmission in the HPTN 071 study communities comes from a wide range of age and sex groups, and there is no outsized contribution to new infections from importation or drug resistance mutations. Men aged 25-39 years, underserved by current treatment and prevention services, should be prioritised for HIV testing and ART. FUNDING: National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AI
Lythgoe KA, Golubchik T, Hall M, et al., 2023, Lineage replacement and evolution captured by 3 years of the United Kingdom Coronavirus (COVID-19) Infection Survey., Proc Biol Sci, Vol: 290
The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens.
Stenseth NC, Schlatte R, Liu X, et al., 2023, Reply to Ekström and Ottersen: Real-time access to data during outbreaks is a key to avoid a local epidemic becoming a global pandemic., Proc Natl Acad Sci U S A, Vol: 120
Fryer HR, Golubchik T, Hall M, et al., 2023, Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias (vol 19, e1011461, 2023), PLOS PATHOGENS, Vol: 19, ISSN: 1553-7366
Abdullahi A, Kida IM, Maina UA, et al., 2023, Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort, Journal of Antimicrobial Chemotherapy, Vol: 78, Pages: 2000-2007, ISSN: 0305-7453
BackgroundDue to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa.AimsWe characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen.MethodsWGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy.ResultsMost participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility—this was characterized by the T66A, G118R, E138K and R263K mutations.ConclusionsThis study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.
Fryer HR, Golubchik T, Hall M, et al., 2023, Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias, PLOS PATHOGENS, Vol: 19, ISSN: 1553-7366
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- Citations: 1
Tsui JL-H, McCrone JT, Lambert B, et al., 2023, Genomic assessment of invasion dynamics of SARS-CoV-2 Omicron BA.1, SCIENCE, Vol: 381, Pages: 336-343, ISSN: 0036-8075
Zewdie K, Pickles M, Floyd S, et al., 2023, Uptake of medical male circumcision with household-based testing, and the association of traditional male circumcision and HIV infection, AIDS, Vol: 37, Pages: 795-802, ISSN: 0269-9370
OBJECTIVES: Voluntary medical male circumcision (VMMC) is an important component of combination HIV prevention. Inclusion of traditionally circumcised HIV negative men in VMMC uptake campaigns may be important if traditional male circumcision is less protective against HIV acquisition than VMMC. METHODS: We used data from the HIV Prevention Trials Network (HPTN) 071 (PopART) study. This cluster-randomized trial assessed the impact of a combination prevention package on population-level HIV incidence in 21 study communities in Zambia and South Africa. We evaluated uptake of VMMC, using a two-stage analysis approach and used discrete-time survival analysis to evaluate the association between the types of male circumcision and HIV incidence. RESULTS: A total of 10 803 HIV-negative men with self-reported circumcision status were included in this study. At baseline, 56% reported being uncircumcised, 26% traditionally circumcised and 18% were medically circumcised. During the PopART intervention, 11% of uncircumcised men reported uptake of medical male circumcision. We found no significant difference in the uptake of VMMC in communities receiving the PopART intervention package and standard of care {adj. rate ratio=1·10 [95% confidence interval (CI) 0.82, 1.50, P = 0.48]}. The rate of HIV acquisition for medically circumcised men was 70% lower than for those who were uncircumcised adjusted hazard ratio (adjHR) = 0.30 (95% CI 0.16-0.55; P < 0.0001). There was no difference in rate of HIV acquisition for traditionally circumcised men compared to those uncircumcised adjHR = 0.84 (95% CI 0.54, 1.31; P = 0.45). CONCLUSIONS: Household-based delivery of HIV testing followed by referral for medical male circumcision did not result in substantial VMMC uptake. Traditional circumcision is not associated with lower risk of HIV acquisition.
Stenseth NC, Schlatte R, Liu X, et al., 2023, How to avoid a local epidemic becoming a global pandemic, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 120, ISSN: 0027-8424
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- Citations: 3
Groves-Kirkby N, Wakeman E, Patel S, et al., 2023, Large-scale calibration and simulation of COVID-19 epidemiologic scenarios to support healthcare planning, EPIDEMICS, Vol: 42, ISSN: 1755-4365
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- Citations: 1
Balakrishna S, Loosli T, Zaheri M, et al., 2023, Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1, Journal of Antimicrobial Chemotherapy, Vol: 78, Pages: 656-664, ISSN: 0305-7453
BackgroundNext-generation sequencing (NGS) is gradually replacing Sanger sequencing (SS) as the primary method for HIV genotypic resistance testing. However, there are limited systematic data on comparability of these methods in a clinical setting for the presence of low-abundance drug resistance mutations (DRMs) and their dependency on the variant-calling thresholds.MethodsTo compare the HIV-DRMs detected by SS and NGS, we included participants enrolled in the Swiss HIV Cohort Study (SHCS) with SS and NGS sequences available with sample collection dates ≤7 days apart. We tested for the presence of HIV-DRMs and compared the agreement between SS and NGS at different variant-calling thresholds.ResultsWe included 594 pairs of SS and NGS from 527 SHCS participants. Males accounted for 80.5% of the participants, 76.3% were ART naive at sample collection and 78.1% of the sequences were subtype B. Overall, we observed a good agreement (Cohen’s kappa >0.80) for HIV-DRMs for variant-calling thresholds ≥5%. We observed an increase in low-abundance HIV-DRMs detected at lower thresholds [28/417 (6.7%) at 10%–25% to 293/812 (36.1%) at 1%–2% threshold]. However, such low-abundance HIV-DRMs were overrepresented in ART-naive participants and were in most cases not detected in previously sampled sequences suggesting high sequencing error for thresholds <3%.ConclusionsWe found high concordance between SS and NGS but also a substantial number of low-abundance HIV-DRMs detected only by NGS at lower variant-calling thresholds. Our findings suggest that a substantial fraction of the low-abundance HIV-DRMs detected at thresholds <3% may represent sequencing errors and hence should not be overinterpreted in clinical practice.
Kendall M, Tsallis D, Wymant C, et al., 2023, Epidemiological impacts of the NHS COVID-19 app in England and Wales throughout its first year, NATURE COMMUNICATIONS, Vol: 14
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- Citations: 3
Fryer HR, Golubchik T, Hall M, et al., 2022, Viral burdens are associated with age and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection related sampling bias
<jats:title>Abstract</jats:title><jats:p>In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burdens, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. Analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior infection, the average Ct value was 0.94 lower among Alpha variant infections, compared those with the predecessor strain, B.1.177. However, among vaccinated individuals, it was 0.34 lower among Delta variant infections, compared to those with the Alpha variant. In addition, the average Ct value decreased by 0.20 for every 10 year age increment of the infected individual. In summary, within-host viral burdens are associated with age, in addition to the interplay of vaccination status and viral variant.</jats:p>
Zhao L, Hall M, de Cesare M, et al., 2022, The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 289, ISSN: 0962-8452
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- Citations: 1
Panovska-Griffiths J, Hinch R, Park J, et al., 2022, Slowly declining growth rates and dynamic reporting delays characterise the Monkeypox epidemic in the UK over May-August 2022
<jats:title>Abstract</jats:title> <jats:p>The monkeypox epidemic in the UK began in May 2022, and subsequently and rather quickly, rates of new cases have declined during August 2022. Identifying the causes of this decline requires accurate estimates of the time-varying epidemic growth rate r(t), which in turn depend upon the reporting delays (defined as the time from onset of symptoms to presenting to healthcare). Using a custom nowcasting method which allows for time-varying delays (EpiLine), we show that the reporting delay for Monkeypox in the UK decreased from an average of 22 days in early May 2022 to 10 days by early June and 7 days in August 2022. Accounting for these dynamic delays shows that the time-varying r(t) declined gradually in the UK over this period. Not accounting for varying time delays would have incorrectly characterised r(t) by a sharp increase followed by a rapid drop. We discuss the importance of this gradual decline, which helps identify the potential mechanisms responsible for the decline in the rate of spread of Monkeypox, which was gradual and started well before vaccines were widely used.</jats:p>
Lehtinen S, Croucher NJ, Blanquart F, et al., 2022, Epidemiological dynamics of bacteriocin competition and antibiotic resistance, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 289, ISSN: 0962-8452
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- Citations: 1
Panovska-Griffiths J, Swallow B, Hinch R, et al., 2022, Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 380, ISSN: 1364-503X
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- Citations: 9
Hinch R, Panovska-Griffiths J, Probert WJM, et al., 2022, Estimating SARS-CoV-2 variant fitness and the impact of interventions in England using statistical and geo-spatial agent-based models, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 380, ISSN: 1364-503X
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- Citations: 5
Overton CE, Pellis L, Stage HB, et al., 2022, EpiBeds: Data informed modelling of the COVID-19 hospital burden in England, PLOS COMPUTATIONAL BIOLOGY, Vol: 18, ISSN: 1553-734X
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- Citations: 2
Blenkinsop A, Monod M, van Sighem A, et al., 2022, Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam, Publisher: eLIFE SCIENCES PUBL LTD
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- Citations: 2
Chaudron SE, Zhao L, Macinthyre-Crockett G, et al., 2022, A rapid, integrated method to monitor HIV viral load, drug resistance, and transmission patterns from finger-prick blood samples, Publisher: JOHN WILEY & SONS LTD, Pages: 19-20
Fogel JM, Wilson EA, Piwowar-Manning E, et al., 2022, HIV drug resistance in a community-randomized trial of universal testing and treatment: HPTN 071 (PopART), JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 25
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- Citations: 1
Moher M, Erickson M, Black P, et al., 2022, Improving Post-Release Care Engagement for People Living with HIV Involved in the Criminal Justice System: A Systematic Review, AIDS AND BEHAVIOR, Vol: 26, Pages: 1607-1617, ISSN: 1090-7165
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- Citations: 2
Ragonnet-Cronin M, Golubchik T, Moyo S, et al., 2022, HIV genetic diversity informs stage of HIV-1 infection among patients receiving antiretroviral therapy in Botswana, The Journal of Infectious Diseases, Vol: 225, Pages: 1330-1338, ISSN: 0022-1899
BackgroundHIV-1 genetic diversity increases during infection and can help infer the time elapsed since infection. However the effect of antiretroviral treatment (ART) on the inference remains unknown.MethodsParticipants with estimated duration of HIV-1 infection based on repeated testing were sourced from cohorts in Botswana (n=1944). Full-length HIV genome sequencing was performed from proviral DNA. We optimized a machine learning model to classify infections as < or >1 year based on viral genetic diversity, demographic and clinical data.ResultsThe best predictive model included variables for genetic diversity of HIV-1 gag, pol and env, viral load, age, sex and ART status. Most participants were on ART. Balanced accuracy was 90.6% (95%CI:86.7%-94.1%). We tested the algorithm among newly diagnosed participants with or without documented negative HIV tests. Among those without records, those who self-reported a negative HIV test within <1 year were more frequently classified as recent than those who reported a test >1 year previously. There was no difference in classification between those self-reporting a negative HIV test <1 year, whether or not they had a record.ConclusionsThese results indicate that recency of HIV-1 infection can be inferred from viral sequence diversity even among patients on suppressive ART.
Magosi LE, Zhang Y, Golubchik T, et al., 2022, Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial - BCPP/Ya Tsie trial, ELIFE, Vol: 11, ISSN: 2050-084X
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- Citations: 3
Wymant C, Bezemer D, Blanquart F, et al., 2022, A highly virulent variant of HIV-1 circulating in the Netherlands, Science, Vol: 375, Pages: 540-545, ISSN: 0036-8075
Changes in viral load and CD4+ T cell decline are expected signals of HIV evolution. By examining data from well-characterized European cohorts, Wymant et al. report an exceptionally virulent subtype of HIV that has been circulating in the Netherlands for several years (see the Perspective by Wertheim). More than one hundred individuals infected with a characteristic subtype B lineage of HIV-1 were found who experienced double the rate of CD4+ cell count declines than expected. By the time they were diagnosed, these individuals were vulnerable to developing AIDS within 2 to 3 years. This virus lineage, which has apparently arisen de novo since around the millennium, shows extensive change across the genome affecting almost 300 amino acids, which makes it hard to discern the mechanism for elevated virulence. —CA
Lythgoe K, Golubchik T, Hall M, et al., 2022, Lineage replacement and evolution captured by three years of the United Kingdom Covid Infection Survey
<jats:title>Abstract</jats:title><jats:p>The Office for National Statistics COVID-19 Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non- SGTF over time. Evolution was characterised by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly in the current phase of the pandemic with routine RT-PCR testing now ended in the community.</jats:p>
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