Imperial College London

ProfessorGrahamCooke

Faculty of MedicineDepartment of Infectious Disease

Professor of Infectious Diseases
 
 
 
//

Contact

 

g.cooke

 
 
//

Location

 

Infectious Diseases SectionMedical SchoolSt Mary's Campus

//

Summary

 

Publications

Publication Type
Year
to

373 results found

Eales O, Wang H, Haw D, Ainslie KEC, Walters C, Atchison C, Cooke G, Barclay W, Ward H, Darzi A, Ashby D, Donnelly C, Elliott P, Riley Set al., 2022, Trends in SARS-CoV-2 infection prevalence during England’s roadmap out of lockdown, January to July 2021, PLoS Computational Biology, ISSN: 1553-734X

Background:Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.Aim:We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.Methods:On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions.Results:Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups.Conclusion:High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.

Journal article

Rimmer S, Barnacle J, Gibani M, Wu M-S, Dissanayake O, Mehta R, Herdman T, Gilchrist M, Muir D, Ebrahimsa U, Mora-Peris B, Dosekun O, Garvey L, Peters J, Davies F, Cooke G, Abbara Aet al., 2022, The clinical presentation of monkeypox: a retrospective case-control study of patients with possible or probable monkeypox in a West London cohort, International Journal of Infectious Diseases, ISSN: 1201-9712

Objectives: Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in non-endemic countries. Our aim was to characterise diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification, and to describe a virtual care model.Methods: We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV PCR testing, 70 were confirmed positive and 70 negative. Data were compared to generate odds ratios of demographic and clinical features.Results: Positive patients were predominantly cis-male (99%) and self-identified as gay, bisexual and other men who have sex with men (GBMSM) (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (OR 7.69 [95% CI 3.58, 16.51]). Positive patients were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) compared with negative controls. 79% of patients engaged with virtual ward follow-up.Conclusions: These data can inform a risk-based approach to management of suspected monkeypox in GBMSM populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPXV outbreak.

Journal article

Whitaker M, Elliott J, Bodinier B, Barclay W, Ward H, Cooke G, Donnelly C, Chadeau M, Elliott Pet al., 2022, Variant-specific symptoms of COVID-19 in a study of 1,542,510 adults in England, Nature Communications, ISSN: 2041-1723

Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study monitored the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell or taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and effects on daily activities will become increasingly important.

Journal article

Mosscrop L, Watber P, Elliot P, Cooke G, Barclay W, Freemont PS, Rosadas C, Taylor GPet al., 2022, Evaluation of the impact of pre-analytical conditions on sample stability for the detection of SARS-CoV-2 RNA, JOURNAL OF VIROLOGICAL METHODS, Vol: 309, ISSN: 0166-0934

Journal article

Alexander J, Liu Z, Munoz Sandoval D, Reynolds C, Ibraheim H, Saifuddin M, Constable L, Altmann D, Balarajah S, Hicks L, Williams H, Teare J, Hart A, Boyton R, Powell Net al., 2022, COVID-19 vaccine-induced antibody and T cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose: a multicentre, prospective, case-control study, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 1005-1015, ISSN: 2468-1253

Background:COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to determine whether immunosuppressive treatments were associated with reduced antibody and T cell responses after a third vaccine dose.Methods:352 adults (72 healthy controls and 280 IBD) were sampled 28-49 days after a third dose of SARS-CoV-2 vaccine. IBD medications studied included thiopurines (n=65), infliximab (n=46), thiopurine/infliximab combination therapy (n=49), ustekinumab (n=44), vedolizumab (n=50) or tofacitinib (n=26). SARS-CoV-2 spike antibody binding and T cell responses were measured. Findings:Geometric mean [geometric SD] anti-S1 RBD antibody concentrations increased in all groups following a third dose, but were significantly lower in patients treated with infliximab (2736.8 U/mL [4.3]; P<0.0001), infliximab and thiopurine combination (1818.3 U/mL [6.7]; P<0.0001) and tofacitinib (8071.5 U/mL [3.1]; P=0.0018) compared to controls (16774.2 U/ml [2.6]). There were no significant differences in anti-S1 RBD antibody concentrations between control subjects and thiopurine (12019.7 U/mL [2.2]; P=0.099), ustekinumab (11089.3 U/mL [2.8]; P=0.060), nor vedolizumab treated patients (13564.9 U/mL [2.4]; P=0.27). In multivariable modelling, lower anti-S1 RBD antibody concentrations were independently associated with infliximab (Geometric mean ratio 0.15, 95% CI 0.11-0.21, P<0.0001), tofacitinib (0.52, 95% CI 0.31-0.87, P=0.012) and thiopurine (0.69, 95% CI 0.51-0.95, P=0.021), but not with ustekinumab (0.64, 95% CI 0.39-1.06, P=0.083), or vedolizumab (0.84, 95% CI 0.54-1.30, P=0.43). Previous SARS-CoV-2 infection (1.58, 95% CI 1.22-2.05, P=0.00056) and older age (0.88, 95% CI 0.80-0.97, P=0.0073) were independently associated with higher and lower anti-S1 antibody concentrations respectively. Antigen specific T cell responses were similar in all groups, except for reci

Journal article

Lucey O, Acana S, Olupot-Olupot P, Muhindo R, Ayikobua R, Uyoga S, Kyeyune D, Cooke G, Maitland Ket al., 2022, High false discovery rate of the Architect anti-HCV screening test in blood donors in Uganda and evaluation of an algorithm for confirmatory testing, Vox Sanguinis: international journal of transfusion medicine, ISSN: 0042-9007

Background and Objectives:Adequate supplies of donor blood remains a major challenge in sub-Saharan Africa. This is exacerbated by lack of confirmatory testing for transfusion transmitted infections by Blood Transfusion Services (BTS) leading to significant blood disposal owing to putatively high seroprevalence rates amongst Ugandan blood donors. We aimed to ascertain the false discoveryrate of the Architect anti-HCV screening assay, categorise screen-reactive samples into 3 groups: presumed false-positive, active and past infection, and develop an algorithm for confirmatory testing.Materials and Methods:470 screen-reactive HCV blood donations were re-tested using the Architect anti-HCV assay, an alternative antibody test (SD biosensor) and a core antigen test. Sample-to-cut-off (S/CO) ratios and pre-analytical factors (centrifugation speed, haemolysis check, time between collection and testing) were recorded. Based on S/CO ratio evaluation, we propose a testing algorithm to guide supplemental tests.Results:The false discovery rate of the Architect anti-HCV assay was 0.84 as 395/470 (84%) screen-reactive samples had no evidence of HCV infection (SD biosensor and core antigen negative) (presumed false-positive). 38/470 (8.1%) were antigenaemic and 32/470 (6.8%) had evidence of past infection.The median S/CO ratios of the presumed false-positive and active infection samples were 1.8 and 17.3 respectively. The positive predictive value of HCV positivity in samples with ratios above 12 was 91.8%. On re-testing, 104/470 (22.1%) samples became negative.Conclusion:The Architect anti-HCV assay has a very high false discovery rate in Ugandan BTSs leading to excessive blood disposal. Pre-analytical factors likely contribute to this. Introduction of confirmatory testing using an algorithm based on S/CO ratio evaluation could limit unnecessary blood wastage and donor deferral.

Journal article

Rafferty H, Cann A, Daunt A, Cooke GSet al., 2022, Changing patterns of clinical presentation of COVID-19 in hospital admissions: With, or because of, COVID?, J Infect, Vol: 85, Pages: e181-e183

Journal article

Chadeau-Hyam M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby J, Whitaker M, Elliott J, Haw D, Walters CE, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott Pet al., 2022, Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys, The Lancet Regional Health Europe, Vol: 21, Pages: 1-11, ISSN: 2666-7762

BackgroundThe Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.MethodsIn the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).FindingsWe estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76–3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0–0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1047, 64.8% (62.4–67.2) were BA.1; N=568, 35.2% (32.8–37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34–0.41). The highest proportion of BA.2 among positives was found in London.InterpretationIn February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.FundingDepartment of Health and Social Care, England.

Journal article

Raya RP, Curtis H, Kulasegaram R, Cooke GS, Burns F, Chadwick D, Sabin CAet al., 2022, The British HIV Association national clinical audit 2021: Management of HIV and hepatitis C coinfection, HIV MEDICINE, ISSN: 1464-2662

Journal article

Siggins MK, Davies K, Fellows R, Thwaites RS, Baillie JK, Semple MG, Openshaw PJM, Zelek WM, Harris CL, Morgan BP, ISARIC4C Investigatorset al., 2022, Alternative pathway dysregulation in tissues drives sustained complement activation and predicts outcome across the disease course in COVID-19, Immunology, ISSN: 0019-2805

Complement, a critical defence against pathogens, has been implicated as a driver of pathology in COVID-19. Complement activation products are detected in plasma and tissues and complement blockade considered for therapy. To delineate roles of complement in immunopathogenesis, we undertook the largest comprehensive study of complement in an COVID-19 to date, a comprehensive profiling of 16 complement biomarkers, including key components, regulators and activation products, in 966 plasma samples from 682 hospitalised COVID-19 patients collected across the hospitalisation period as part of the UK ISARIC4C study. Unsupervised clustering of complement biomarkers mapped to disease severity and supervised machine learning identified marker sets in early samples that predicted peak severity. Compared to heathy controls, complement proteins and activation products (Ba, iC3b, terminal complement complex) were significantly altered in COVID-19 admission samples in all severity groups. Elevated alternative pathway activation markers (Ba and iC3b) and decreased alternative pathway regulator (properdin) in admission samples associated with more severe disease and risk of death. Levels of most complement biomarkers were reduced in severe disease, consistent with consumption and tissue deposition. Latent class mixed modelling and cumulative incidence analysis identified the trajectory of increase of Ba to be a strong predictor of peak COVID-19 disease severity and death. The data demonstrate that early-onset, uncontrolled activation of complement, driven by sustained and progressive amplification through the alternative pathway amplification loop is a ubiquitous feature of COVID-19, further exacerbated in severe disease. These findings provide novel insights into COVID-19 immunopathogenesis and inform strategies for therapeutic intervention.

Journal article

Eales O, Ainslie KEC, Walters CE, Wang H, Atchison C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley Set al., 2022, Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number, Epidemics: the journal of infectious disease dynamics, Vol: 40, ISSN: 1755-4365

The time-varying reproduction number () can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of from case data. However, these are not easily adapted to point prevalence data nor can they infer across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020–December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of over the period of two subsequent rounds (6–8 weeks) and single rounds (2–3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in over the summer of 2020 as restrictions were eased, and a reduction in during England’s second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.

Journal article

Elliott P, Eales O, Bodinier B, Tang D, Wang H, Jonnerby LJA, Haw D, Elliott J, Whitaker M, Walters C, Atchison C, Diggle P, Page A, Trotter A, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke G, Chadeau M, Donnelly Cet al., 2022, Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England, Nature Communications, Vol: 13, ISSN: 2041-1723

Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n=102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R=0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.

Journal article

Atchison C, Moshe M, Brown J, Whitaker M, Wong N, Bharath A, Mckendry R, Darzi A, Ashby D, Donnelly C, Riley S, Elliott P, Barclay W, Cooke G, Ward Het al., 2022, Validity of self-testing at home with rapid SARS-CoV-2 antibody detection by lateral flow immunoassay, Clinical Infectious Diseases, ISSN: 1058-4838

Background: We explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassay (LFIA) performance under field conditions compared to laboratory-based ELISA and live virus neutralisation. Methods: In July 2021, 3758 participants performed, at home, a self-administered LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample for assessment of IgG antibodies using the Roche Elecsys® Anti-SARS-CoV-2 assay. We compared the self-reported LFIA result to the quantitative Roche assay and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralisation. Results: Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on Roche (using the manufacturer reference standard threshold for positivity of 0.8 U ml−1). Live virus neutralisation was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% CI 71.8, 84.6), 142/155 (91.6%; 86.1, 95.5) with ALFA, and 169 (100%; 97.8, 100.0) with Roche. There were 81 samples with no detectable virus neutralisation; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI 46.5, 68.9), 34/75 (45.3%; 33.8, 57.3) with ALFA, and 0/81 (0%; 0.0, 4.5) with Roche. Conclusions: Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ELISA with virus neutralisation.

Journal article

Eales O, Martins LDO, Page AJ, Wang H, Bodinier B, Tang D, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly CA, Chadeau-Hyam Met al., 2022, Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England, Nature Communications, Vol: 13, ISSN: 2041-1723

The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England’s Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the ‘new normal’.

Journal article

Eales O, Wang H, Bodinier B, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Chadeau M, Donnelly C, Elliott Pet al., 2022, SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334

Background: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September - 27 September 2021) and 15 (19 October - 5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month.Results: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI, 8%-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England.Conclusions: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.

Journal article

Lee IR, Tong SYC, Davis JS, Paterson DL, Syed-Omar SF, Peck KR, Chung DR, Cooke GS, Libau EA, Rahman S-NBA, Gandhi MP, Shi L, Zheng S, Chaung J, Tan SY, Kalimuddin S, Archuleta S, Lye DCet al., 2022, Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial, TRIALS, Vol: 23

Journal article

Barnes E, Cooke GS, Lauer GM, Chung RTet al., 2022, Implementation of a controlled human infection model for evaluation of HCV vaccine candidates, HEPATOLOGY, ISSN: 0270-9139

Journal article

Eales O, de Oliveira Martins L, Page A, Wang H, Bodinier B, Tang D, Haw D, Jonnerby LJA, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly C, Chadeau Met al., 2022, Dynamics and scale of the SARS-CoV-2 variant Omicron epidemic in England, Nature Communications, ISSN: 2041-1723

Journal article

Wong N, Meshkinfamfard S, Turbé V, Whitaker M, Moshe M, Bardanzellu A, Dai T, Pignatelli E, Barclay W, Darzi A, Elliott P, Ward H, Tanaka R, Cooke G, McKendry R, Atchison C, Bharath Aet al., 2022, Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies, Communications Medicine, Vol: 2, ISSN: 2730-664X

Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home but rely on subjective interpretation of a test line by eye, risking false positives and negatives. Here we report the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity. Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Automated analysis showed substantial agreement with human experts (Kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets). Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues. Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false positive and false negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests, to be a tool for improved accuracy for population-level community surveillance.

Journal article

Joshi M, Ashrafian H, Arora S, Sharabiani M, Kenny M, Sadia K, Cooke G, Ara Det al., 2022, A pilot study to investigate real time digital alerting from wearable sensors in surgical patients, Pilot and Feasibility Studies, Vol: 8, ISSN: 2055-5784

Background Continuous vital sign monitoring may identify changes sooner than current standard monitoring. Objective To investigate if the use of real time digital alerts sent to healthcare staff can improve the time taken to identify unwell patients and those with sepsis. DesignA prospective cohort study design. Setting West Middlesex University Hospital, UK. Participants 50 acutely unwell surgical patients admitted to hospital. Intervention Patients wore a lightweight wearable sensor measuring heart rate (HR), respiratory rate (RR) and temperature every 2 minutes whilst standard intermittent ward monitoring of vital signs was performed by nurses. Digital alerts were sent to healthcare staff from the sensor to a smartphone device. All alerts were reviewed for recruited patients to identify the exact time on the sensor in which deterioration occurred. The time to acknowledgement was then reviewed for each action and an average time to acknowledgement calculated.Results There were 50 patients recruited in the pilot study, of which there were vital sign alerts in 18 patients (36%). The total number of vital sign alerts generated in these 18 patients was 51. Of these 51 alerts there 7 alerts for high HR (13.7%), 33 for RR (64.7%) and 11 for temperature (21.6%). Out of the 27 acknowledged alerts there were 2 alerts for HR, 17 for RR and 8 for temperature. The average time to staff acknowledgement of the notification for all alerts was 154 minutes (2.6 hours). There were some patients which had shown signs of deterioration in the cohort. The frequency of routine observation monitoring was increased in 2 cases, 3 patients were referred to a senior clinician and 2 patients were initiated on the sepsis pathway. Conclusion This study demonstrates the evaluation of digital alerts to nurses in real-time. Although not all alerts were acknowledged, deterioration on the ward observations was detected and actions were taken accordingly. Patients were started on the sepsis pathw

Journal article

Whittaker C, Watson O, Alvarez-Moreno C, Angkasekwinai N, Boonyasiri A, Triana LC, Chanda D, Charoenpong L, Chayakulkeeree M, Cooke G, Croda J, Cucunubá ZM, Djaafara A, Estofolete CF, Grillet M-E, Faria N, Costa SF, Forero-Peña DA, Gibb DM, Gordon A, Hamers RL, Hamlet A, Irawany V, Jitmuang A, Keurueangkul N, Kimani TN, Lampo M, Levin A, Lopardo G, Mustafa R, Nayagam AS, Ngamprasertchai T, Njeri NIH, Nogueira ML, Ortiz-Prado E, Perroud Jr MW, Phillips AN, Promsin P, Qavi A, Rodger AJ, Sabino EC, Sangkaew S, Sari D, Sirijatuphat R, Sposito AC, Srisangthong P, Thompson H, Udwadia Z, Valderrama-Beltrán S, Winskill P, Ghani A, Walker P, Hallett Tet al., 2022, Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis, Clinical Infectious Diseases, Vol: 75, Pages: e224-e233, ISSN: 1058-4838

BackgroundThe public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear.MethodsUsing a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care.ResultsThe impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics.ConclusionsAdvances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Journal article

Flower B, Du Hong D, Vu Thi Kim H, Pham Minh K, Geskus RB, Day J, Cooke GSet al., 2022, Seroprevalence of Hepatitis B, C and D in Vietnam: A systematic review and meta-analysis., The Lancet Regional Health - Western Pacific, Vol: 24, Pages: 1-20, ISSN: 2666-6065

Background: Vietnam has one of the greatest disease burdens from chronic viral hepatitis. Comprehensive prevalence data are essential to support its elimination as a public health threat. Methods: We searched Medline and Embase from 1990 to 2021 for seroprevalence data relating to Hepatitis B (HBV), C (HCV) and D (HDV) in Vietnam. We estimated pooled prevalence with a DerSimonian-Laird random-effects model and stratified study populations into i) low-risk ii) high-risk exposure and iii) liver disease. We further estimated prevalence by decade and region and rates of HIV-coinfection. Findings: We analysed 72 studies, including 120 HBV, 114 HCV and 23 HDV study populations. Pooled HBV prevalence was low in blood donors (1.86% [1.82-1.90]) but high in antenatal populations (10.8% [10.1-11.6]) and adults in the general population (10.5% [10.0-11.0]). It was similar or modestly increased in groups at highest risk of exposure, suggesting the epidemic is largely driven by chronic infections acquired in childhood. HCV pooled prevalence in the general population was lower than historical estimates: 0.26% (0.09-0.51) have active infection defined by detectable antigen or HCV RNA. In contrast, there is an extremely high prevalence of active HCV infection in people who inject drugs (PWID) (57.8% [56.5-59.1]), which has persisted through the decades despite harm-reduction interventions. HDV appears mainly confined to high-risk groups. Interpretation: Blood safety has improved, but renewed focus on HBV vaccination at birth and targeted HCV screening and treatment of PWID are urgently required to meet elimination targets. Large cross-sectional studies are needed to better characterize HDV prevalence, but mass screening may not be warranted. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Journal article

Chadeau M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby LJA, Whitaker M, Elliott J, Haw D, Walters C, Atchison C, Diggle P, Page A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly C, Elliott Pet al., 2022, Cross-sectional community surveys to monitor the Omicron SARS-CoV-2 epidemic in England during February 2022, The Lancet Regional Health Europe, ISSN: 2666-7762

Background: The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).Findings: We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76–3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0–0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1,047, 64.8% (62.4–67.2) were BA.1; N=568, 35.2% (32.8–37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34–0.41). The highest proportion of BA.2 among positives was found in London. Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.Funding Department of Health and Social Care, England.

Journal article

Wang T, Smith DA, Campbell C, Freeman O, Moysova Z, Noble T, Varnai KA, Harris S, Salih H, Roadknight G, Little S, Glampson B, Mercuri L, Papadimitriou D, Jones CR, Taylor V, Chaudhry A, Phan H, Borca F, Olza J, Warricker F, Romao L, Ramlakhan D, English L, Klenerman P, Andersson M, Collier J, Stockdale AJ, Todd S, McIntyre K, Frankland A, Nastouli E, Khakoo S, Gelson W, Cooke GS, Woods K, Davies J, Barnes E, Matthews PCet al., 2022, Cohort Profile: The National Institute for Health Research Health Informatics Collaborative: Hepatitis B Virus (NIHR HIC HBV) research dataset, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, ISSN: 0300-5771

Journal article

Eales O, Wang H, Haw D, Ainslie KEC, Walters CE, Atchison C, Cooke G, Barclay W, Ward H, Darzi A, Ashby D, Donnelly CA, Elliott P, Riley Set al., 2022, Trends in SARS-CoV-2 infection prevalence during England’s roadmap out of lockdown, January to July 2021

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (<jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub>) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub> of each relaxation of restrictions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub> incre

Journal article

Chadeau M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Elliott J, Walters C, Jonnerby LJA, Atchison C, Diggle P, Page A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly C, Elliott Pet al., 2022, Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study, EClinicalMedicine, Vol: 48, Pages: 1-14, ISSN: 2589-5370

Background: Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years. Methods: SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N= 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses. Findings: Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted odds ratio of 0.36 (0.25, 0.53). Interpretation: Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.

Journal article

Garvey L, Cooke GS, 2022, Engaging with HCV reinfection to advance microelimination., Lancet HIV, Vol: 9, Pages: e372-e374

Journal article

Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Simmons B, Klaber B, Elliott P, Darzi A, Riley S, Ashby D, Martin P, Gleeson S, Willicombe M, Kelleher P, Ward H, Barclay WS, Cooke GSet al., 2022, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study [version 2; peer review: 2 approved], Wellcome Open Research, Vol: 6, ISSN: 2398-502X

Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.

Journal article

Whitaker M, Elliott J, Bodinier B, Barclay W, Ward H, Cooke G, Donnelly CA, Chadeau-Hyam M, Elliott Pet al., 2022, Variant-specific symptoms of COVID-19 among 1,542,510 people in England

<jats:title>Abstract</jats:title><jats:p>Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important.</jats:p>

Journal article

Lazarus JV, Picchio CA, Byrne CJ, Crespo J, Colombo M, Cooke GS, Dore GJ, Grebely J, Ward JW, Dillon JFet al., 2022, A Global Systematic Review of Hepatitis C Elimination Efforts through Micro-Elimination, SEMINARS IN LIVER DISEASE, Vol: 42, Pages: 159-172, ISSN: 0272-8087

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00420047&limit=30&person=true