Imperial College London

ProfessorGrahamCooke

Faculty of MedicineDepartment of Infectious Disease

Professor of Infectious Diseases
 
 
 
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g.cooke

 
 
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Infectious Diseases SectionMedical SchoolSt Mary's Campus

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Summary

 

Publications

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296 results found

Burdett A, Toumazou C, Sahoo R, Mujan A, Hon T-K, Bedzo-Nutakor J, Casali N, Karvela M, Sohbati M, Cooke GS, Davies GW, Moore LSPet al., 2021, Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing, BMC Infectious Diseases, Vol: 21, Pages: 1-10, ISSN: 1471-2334

BackgroundAs SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients’ samples.MethodWe tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficiency and utility of CovidNudge (i) for detection in individuals’ sputum (compared to nasopharyngeal swabs), (ii) for detection in pooled sputum samples, and (iii) by modelling roll out scenarios for pooled sputum testing.ResultsAcross 295 paired samples, we find no difference (p = 0.1236) in signal strength for sputum (mean amplified replicates (MAR) 25.2, standard deviation (SD) 14.2, range 0–60) compared to nasopharyngeal swabs (MAR 27.8, SD 12.4, range 6–56). At 10-sample pool size we find some drop in absolute strength of signal (individual sputum MAR 42.1, SD 11.8, range 13–60 vs. pooled sputum MAR 25.3, SD 14.6, range 1–54; p < 0.0001), but only marginal drop in sensitivity (51/53,96%). We determine a limit of detection of 250 copies/ml for an individual test, rising only four-fold to 1000copies/ml for a 10-sample pool. We find optimal pooled testing efficiency to be a 12–3-1-sample model, yet as prevalence increases, pool size should decrease; at 5% prevalence to maintain a 75% probability of negative first test, 5-sample pools are optimal.ConclusionWe describe for the first time the use of sequentially dipped sputum samples for rapid pooled point of care SARS-CoV-2 PCR testing. The potential to screen asymptomatic cohorts rapidly, at the point-of-care, with PCR, offers the potential to quickly identify and isolate positive individuals within a population “bubble”.

Journal article

Durkin S, Britton C, Cooke G, Mehta Ret al., 2021, A case of invasive meningococcal disease presenting as myopericarditis, Clinical Infection in Practice, Vol: 12, ISSN: 2590-1702

BackgroundNeisseria meningitidis is a universally-feared Gram negative diplococcus, and infection confers high rates of morbidity and mortality despite effective antimicrobial therapy. Invasive meningococcal disease most commonly presents with meningococcaemia or meningococcal meningitis.Case report72-year-old female, previously fit and well, was admitted with chest pain, and associated breathlessness and diarrhoea. The clinical picture was of a myopericarditis.ResultsInitial electrocardiogram (ECG) changes and elevated troponin were consistent with myopericarditis. Neisseria meningitidis W135 was cultured from blood, and subsequently from cerebrospinal fluid (CSF). Leptomeningeal meningitis and ventriculitis was evident on magnetic resonance imaging (MRI) of the brain. Treatment was commenced with intravenous ceftriaxone. The clinical course was complicated by pneumonia, influenza A infection, and fatal pulmonary embolism.ConclusionsThis case demonstrates the range of clinical features of invasive meningococcal disease, highlighting in particular that meningococcal bacteraemia can present clinically as myopericarditis, which may be present in a substantial proportion of cases. Prompt antimicrobial therapy, as well as an awareness of potential complications, are paramount in the clinical management of meningococcal myopericarditis.

Journal article

Vollmer MAC, Radhakrishnan S, Kont MD, Flaxman S, Bhatt SJ, Costelloe C, Honeyford K, Aylin P, Cooke G, Redhead J, Sanders A, Mangan H, White PJ, Ferguson N, Hauck K, Perez Guzman PN, Nayagam Set al., 2021, The impact of the COVID-19 pandemic on patterns of attendance at emergency departments in two large London hospitals: an observational study, BMC Health Services Research, ISSN: 1472-6963

Background Hospitals in England have undergone considerable change to address the surgein demand imposed by the COVID-19 pandemic. The impact of this on emergencydepartment (ED) attendances is unknown, especially for non-COVID-19 related emergencies.Methods This analysis is an observational study of ED attendances at the Imperial CollegeHealthcare NHS Trust (ICHNT). We calibrated auto-regressive integrated moving averagetime-series models of ED attendances using historic (2015-2019) data. Forecasted trendswere compared to present year ICHNT data for the period between March 12, 2020 (whenEngland implemented the first COVID-19 public health measure) and May 31, 2020. Wecompared ICHTN trends with publicly available regional and national data. Lastly, wecompared hospital admissions made via the ED and in-hospital mortality at ICHNT duringthe present year to the historic 5-year average.Results ED attendances at ICHNT decreased by 35% during the period after the firstlockdown was imposed on March 12, 2020 and before May 31, 2020, reflecting broadertrends seen for ED attendances across all England regions, which fell by approximately 50%for the same time frame. For ICHNT, the decrease in attendances was mainly amongst thoseaged <65 years and those arriving by their own means (e.g. personal or public transport) andnot correlated with any of the spatial dependencies analysed such as increasing distance frompostcode of residence to the hospital. Emergency admissions of patients without COVID-19after March 12, 2020 fell by 48%; we did not observe a significant change to the crudemortality risk in patients without COVID-19 (RR 1.13, 95%CI 0.94-1.37, p=0.19).Conclusions Our study findings reflect broader trends seen across England and give anindication how emergency healthcare seeking has drastically changed. At ICHNT, we findthat a larger proportion arrived by ambulance and that hospitalisation outcomes of patientswithout COVID-19 did not differ from previous years. The ext

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., 2021, Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis, Clinical Infectious Diseases, ISSN: 1058-4838

Journal article

Elliott J, Whitaker M, Bodinier B, Eales O, Riley S, Ward H, Cooke G, Darzi A, Chadeau M, Elliott Pet al., 2021, Predictive symptoms for COVID-19 in the community: REACT-1 study of over one million people, PLoS Medicine, ISSN: 1549-1277

Background:Rapid detection, isolation and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and whether predictive symptoms differ between B.1.1.7 (Alpha) lineage (predominating as of April 2021in the USA, UK and elsewhere) and wild type.Methods and Findings:We obtained throat and nose swabs with valid SARS-CoV-2 polymerase chain reaction (PCR) test results from 1,147,370 volunteers aged 5 years and above (6,450 positives) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least one symptom identified seven symptoms as jointly and positively predictive of PCR positivity in rounds 2–7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss and muscle aches. The resulting model (rounds 2–7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same seven symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. Main

Journal article

Neumann I, Schünemann HJ, Bero L, Cooke G, Magrini N, Moja Let al., 2021, Global access to affordable direct oral anticoagulants, Bulletin of the World Health Organization, Vol: 99, Pages: 653-660, ISSN: 0042-9686

Poor control of cardiovascular disease accounts for a substantial proportion of the disease burden in developing countries, but often essential anticoagulant medicines for preventing strokes and embolisms are not widely available. In 2019, direct oral anticoagulants were added to the World Health Organization's WHO Model list of essential medicines. The aims of this paper are to summarize the benefits of direct oral anticoagulants for patients with cardiovascular disease and to discuss ways of increasing their usage internationally. Although the cost of direct oral anticoagulants has provoked debate, the affordability of introducing these drugs into clinical practice could be increased by: price negotiation; pooled procurement; competitive tendering; the use of patent pools; and expanded use of generics. In 2017, only 14 of 137 countries that had adopted national essential medicines lists included a direct oral anticoagulant on their lists. This number could increase rapidly if problems with availability and affordability can be tackled. Once the types of patient likely to benefit from direct oral anticoagulants have been clearly defined in clinical practice guidelines, coverage can be more accurately determined and associated costs can be better managed. Government action is required to ensure that direct oral anticoagulants are covered by national budgets because the absence of reimbursement remains an impediment to achieving universal coverage. Tackling cardiovascular disease with the aid of direct oral anticoagulants is an essential component of efforts to achieve the World Health Organization's target of reducing premature deaths due to noncommunicable disease by 25% by 2025.

Journal article

Eales O, Walters C, Wang H, Haw D, Ainslie K, Atchison C, Page A, Prosolek S, Trotter A, Viet TL, Alikhan N-F, Jackson LM, Ludden C, COG UK TCGUKC, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley Set al., 2021, Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2

BackgroundCommunity surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administeredthroat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community.MethodsDuring round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines.ResultsWe estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportionof positive individuals detected on first swab, was found to be higher 𝑃 for those with an 0 initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in socialdistancing measures.DiscussionHome self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has hig

Working paper

Redd R, Cooper E, Atchison C, Pereira I, Hollings P, Cooper T, Millar C, Ashby D, Riley S, Darzi A, Barclay W, Cooke GS, Elliott P, Donnelly CA, Ward Het al., 2021, Behavioural responses to SARS-CoV-2 antibody testing in England: REACT-2 study, Wellcome Open Research, Vol: 6, Pages: 203-203

<ns3:p><ns3:bold>Background:  </ns3:bold>This study assesses the behavioural responses to SARS-CoV-2 antibody test results as part of the REal-time Assessment of Community Transmission-2 (REACT-2) research programme, a large community-based surveillance study of antibody prevalence in England.</ns3:p><ns3:p> <ns3:bold>Methods:</ns3:bold> A follow-up survey was conducted six weeks after the SARS-CoV-2 antibody test. The follow-up survey included 4500 people with a positive result and 4039 with a negative result. Reported changes in behaviour were assessed using difference-in-differences models. A nested interview study was conducted with 40 people to explore how they thought through their behavioural decisions.</ns3:p><ns3:p> <ns3:bold>Results:</ns3:bold> While respondents reduced their protective behaviours over the six weeks, we did not find evidence that positive test results changed participant behaviour trajectories in relation to the number of contacts the respondents had, for leaving the house to go to work, or for leaving the house to socialise in a personal place. The qualitative findings supported these results. Most people did not think that they had changed their behaviours because of their test results, however they did allude to some changes in their attitudes and perceptions around risk, susceptibility, and potential severity of symptoms.</ns3:p><ns3:p> <ns3:bold>Conclusions: </ns3:bold>We found limited evidence that knowing your antibody status leads to behaviour change in the context of a research study. While this finding should not be generalised to widespread self-testing in other contexts, it is reassuring given the importance of large prevalence studies, and the practicalities of doing these at scale using self-testing with lateral flow immunoassay (LFIA).</ns3:p>

Journal article

Elliott P, Haw D, Wang H, Eales O, Walters C, Ainslie K, Atchison C, Fronterre C, Diggle P, Page A, Trotter A, Prosolek S, COG-UK TCGUKC, Ashby D, Donnelly C, Barclay W, Cooke G, Ward H, Darzi A, Riley Set al., 2021, REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during May to July 2021

BackgroundThe prevalence of SARS-CoV-2 infection continues to drive rates of illness andhospitalisations despite high levels of vaccination, with the proportion of cases caused by theDelta lineage increasing in many populations. As vaccination programs roll out globally andsocial distancing is relaxed, future SARS-CoV-2 trends are uncertain.MethodsWe analysed prevalence trends and their drivers using reverse transcription-polymerasechain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June2021) and round 13 (between 24 June and 12 July 2021) of the REal-time Assessment ofCommunity Transmission-1 (REACT-1) study, with swabs sent to non-overlapping randomsamples of the population ages 5 years and over in England.ResultsWe observed sustained exponential growth with an average doubling time in round 13 of 25days (lower Credible Interval of 15 days) and an increase in average prevalence from 0.15%(0.12%, 0.18%) in round 12 to 0.63% (0.57%, 0.18%) in round 13. The rapid growth acrossand within rounds appears to have been driven by complete replacement of Alpha variant byDelta, and by the high prevalence in younger less-vaccinated age groups, with a nine-foldincrease between rounds 12 and 13 among those aged 13 to 17 years. Prevalence amongthose who reported being unvaccinated was three-fold higher than those who reported beingfully vaccinated. However, in round 13, 44% of infections occurred in fully vaccinatedindividuals, reflecting imperfect vaccine effectiveness against infection despite high overalllevels of vaccination. Using self-reported vaccination status, we estimated adjusted vaccineeffectiveness against infection in round 13 of 49% (22%, 67%) among participants aged 18to 64 years, which rose to 58% (33%, 73%) when considering only strong positives (Cyclethreshold [Ct] values < 27); also, we estimated adjusted vaccine effectiveness againstsymptomatic infection of 59% (23%, 78%), with any one of three common COVID-19symptoms reported

Working paper

Simmons B, Ariyoshi K, Ohmagari N, Pulcini C, Huttner B, Gandra S, Satta G, Moja L, Sharland M, Magrini N, Miraldo M, Cooke Get al., 2021, Progress towards antibiotic use targets in eight high-income countries, Bulletin of the World Health Organization, Vol: 99, Pages: 550-561, ISSN: 0042-9686

Objective To compare antibiotic sales in eight high-income countries using the 2019 World Health Organization (WHO) Access, Watch andReserve (AWaRe) classification and the target of 60% consumption of Access category antibiotics.Methods We analysed data from a commercial database of sales of systemic antibiotics in France, Germany, Italy, Japan, Spain, Switzerland,United Kingdom of Great Britain and Northern Ireland, and United States of America over the years 2013–2018. We classified antibioticsaccording to the 2019 AWaRe categories: Access, Watch, Reserve and Not Recommended. We measured antibiotic sales per capita in standardunits (SU) per capita and calculated Access group sales as a percentage of total antibiotic sales.Findings In 2018, per capita antibiotic sales ranged from 7.4 SU (Switzerland) to 20.0 SU (France); median sales of Access group antibioticswere 10.9 SU per capita (range: 3.5–15.0). Per capita sales declined moderately over 2013–2018. The median percentage of Access groupantibiotics was 68% (range: 22–77 %); the Access group proportion increased in most countries between 2013 and 2018. Five countriesexceeded the 60% target; two countries narrowly missed it (>55% in Germany and Italy). Sales of Access antibiotics in Japan were low(22%), driven by relatively high sales of oral cephalosporins and macrolides.Conclusion We have identified changes to prescribing that could allow countries to achieve the WHO target. The 60% Access group targetprovides a framework to inform national antibiotic policies and could be complemented by absolute measures and more ambitious valuesin specific settings.

Journal article

Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA, Wootton DG, Sigfrid L, Harrison EM, Docherty AB, de Silva T, Egan C, Pius R, Hardwick HE, Merson L, Girvan M, Dunning J, Nguyen-Van-Tam JS, Openshaw PJM, Baillie JK, Semple MG, Ho Aet al., 2021, Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study, The Lancet Microbe, Vol: 2, Pages: E354-E365, ISSN: 2666-5247

BackgroundMicrobiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19.MethodsThe International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study is an ongoing, prospective cohort study recruiting inpatients from 260 hospitals in England, Scotland, and Wales, conducted by the ISARIC Coronavirus Clinical Characterisation Consortium. Patients with a confirmed or clinician-defined high likelihood of SARS-CoV-2 infection were eligible for inclusion in the ISARIC WHO CCP-UK study. For this specific study, we excluded patients with a recorded negative SARS-CoV-2 test result and those without a recorded outcome at 28 days after admission. Demographic, clinical, laboratory, therapeutic, and outcome data were collected using a prespecified case report form. Organisms considered clinically insignificant were excluded.FindingsWe analysed data from 48 902 patients admitted to hospital between Feb 6 and June 8, 2020. The median patient age was 74 years (IQR 59–84) and 20 786 (42·6%) of 48 765 patients were female. Microbiological investigations were recorded for 8649 (17·7%) of 48 902 patients, with clinically significant COVID-19-related respiratory or bloodstream culture results recorded for 1107 patients. 762 (70·6%) of 1080 infections were secondary, occurring more than 2 days after hospital admission. Staphylococcus aureus and Haemophilus influenzae were the most common pathogens causing respiratory co-infections (diagnosed ≤2 days after admission), with Enterobacteriaceae and S aureus most common in secondary respiratory infections. Bloodstream infections were most frequently caused by Escherichia coli a

Journal article

Hamady A, Cooke GS, Garvey LJ, 2021, Identification of hepatitis delta superinfection when investigating transaminitis in HIV/hepatitis B virus co-infection., AIDS, Vol: 35, Pages: 1704-1706

Hepatitis delta virus (HDV) is a highly pathogenic virus which can cause rapidly progressive liver disease in individuals with chronic hepatitis B virus and for which treatment options are limited. The incidence of sexually transmitted HDV infection is unknown. Here we report the case of a HDV seronegative man with pre-existent HIV/hepatitis B virus, taking effective tenofovir-containing antiretroviral therapy, who experienced a significant acute transaminitis with HDV antibody seroconversion and viraemia and no other identifiable cause.

Journal article

Flower B, McCabe L, Le Ngoc C, Le Manh H, Le Thanh P, Dang Trong T, Vo Thi T, Vu Thi Kim H, Nguyen Tat T, Phan Thi Hong D, Nguyen Thi Chau A, Dinh Thi T, Tran Thi Tuyet N, Tarning J, Kingsley C, Kestelyn E, Pett SL, Thwaites G, Nguyen Van VC, Smith D, Barnes E, Ansari A, Turner H, Rahman M, Walker AS, Day J, Cooke GSet al., 2021, High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: the Vietnam SEARCH study, Open Forum Infectious Diseases, Vol: 8, ISSN: 2328-8957

BackgroundGenotype 6 is the most genetically diverse lineage of hepatitis C virus (HCV), and predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the lowest costing treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis.MethodsIn this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/ml at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/ml received 24 weeks. Primary endpoint was sustained virological response.FindingsOf 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a, 34% 6e. The remainder had 6h, 6k, 6l or 6o. 100% had viral load <500 IU/ml by day 14, meaning all received 12 weeks of SOF/DCV. 100% achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions (RAS) at baseline.Interpretation12 weeks of SOF/DCV achieves excellent cure rates in this population. This data supports the removal of costly genotyping in countries where genotype 3 prevalence in <5%, in keeping with WHO guidelines. NS5A-resistance associated mutations in isolation, do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.

Journal article

Ward H, Atchison C, Whitaker M, Donnelly CA, Riley S, Ashby D, Darzi A, Barclay WS, Cooke G, Elliott Pet al., 2021, Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The second wave of infection in England is apparen

Journal article

Drake TM, Riad AM, Fairfield CJ, Egan C, Knight SR, Pius R, Hardwick HE, Norman L, Shaw CA, McLean KA, Thompson AAR, Ho A, Swann OV, Sullivan M, Soares F, Holden KA, Merson L, Plotkin D, Sigfrid L, de Silva TI, Girvan M, Jackson C, Russell CD, Dunning J, Solomon T, Carson G, Olliaro P, Nguyen-Van-Tam JS, Turtle L, Docherty AB, Openshaw PJ, Baillie JK, Harrison EM, Semple MG, ISARIC4C investigatorset al., 2021, Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study, The Lancet, Vol: 398, Pages: 223-237, ISSN: 0140-6736

BACKGROUND: COVID-19 is a multisystem disease and patients who survive might have in-hospital complications. These complications are likely to have important short-term and long-term consequences for patients, health-care utilisation, health-care system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and effect of COVID-19 complications, particularly in those who survive, using the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK. METHODS: We did a prospective, multicentre cohort study in 302 UK health-care facilities. Adult patients aged 19 years or older, with confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 were included in the study. The primary outcome of this study was the incidence of in-hospital complications, defined as organ-specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities. FINDINGS: Between Jan 17 and Aug 4, 2020, 80 388 patients were included in the study. Of the patients admitted to hospital for management of COVID-19, 49·7% (36 367 of 73 197) had at least one complication. The mean age of our cohort was 71·1 years (SD 18·7), with 56·0% (41 025 of 73 197) being male and 81·0% (59 289 of 73 197) having at least one comorbidity. Males and those aged older than 60 years were most likely to have a complication (aged ≥60 years: 54·5% [16 579 of 30 416] in males and 48·2% [11 707 of 24 288] in females; aged <60 years: 48·8% [5179 of 10 609] in males and 36·6% [2814 of 7689] in females). Renal (24·3%, 17 752 of 73 197), complex respiratory (18·4%, 13 486 of 73 197), and systemic (16·3%, 11 895 of 73 197) complications were

Journal article

Lazarus JV, Safreed-Harmon K, Kamarulzaman A, Anderson J, Leite RB, Behrens G, Bekker L-G, Bhagani S, Brown D, Brown G, Buchbinder S, Caceres C, Cahn PE, Carrieri P, Caswell G, Cooke GS, Monforte AD, Dedes N, del Amo J, Elliott R, El-Sadr WM, Fuster-Ruiz de Apodaca MJ, Guaraldi G, Hallett T, Harding R, Hellard M, Jaffar S, Kall M, Klein M, Lewin SR, Mayer K, Perez-Molina JA, Moraa D, Naniche D, Nash D, Noori T, Pozniak A, Rajasuriar R, Reiss P, Rizk N, Rockstroh J, Romero D, Sabin C, Serwadda D, Waters Let al., 2021, Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV, NATURE COMMUNICATIONS, Vol: 12

Journal article

Ward H, Whitaker M, Tang SN, Atchison C, Darzi A, Donnelly C, Diggle P, Ashby D, Riley S, Barclay W, Elliott P, Cooke Get al., 2021, Vaccine uptake and SARS-CoV-2 antibody prevalence among 207,337 adults during May 2021 in England: REACT-2 study

Background The programme to vaccinate adults in England has been rapidly implementedsince it began in December 2020. The community prevalence of SARS-CoV-2 anti-spikeprotein antibodies provides an estimate of total cumulative response to natural infection andvaccination. We describe the distribution of SARS-CoV-2 IgG antibodies in adults inEngland in May 2021 at a time when approximately 7 in 10 adults had received at least onedose of vaccine.Methods Sixth round of REACT-2 (REal-time Assessment of Community Transmission-2),a cross-sectional random community survey of adults in England, from 12 to 25 May 2021;207,337 participants completed questionnaires and self-administered a lateral flowimmunoassay test producing a positive or negative result.Results Vaccine coverage with one or more doses, weighted to the adult population inEngland, was 72.9% (95% confidence interval 72.7-73.0), varying by age from 25.1% (24.5-25.6) of those aged 18 to 24 years, to 99.2% (99.1-99.3) of those 75 years and older. Inadjusted models, odds of vaccination were lower in men (odds ratio [OR] 0.89 [0.85-0.94])than women, and in people of Black (0.41 [0.34-0.49]) compared to white ethnicity. Therewas higher vaccine coverage in the least deprived and highest income households. Peoplewho reported a history of COVID-19 were less likely to be vaccinated (OR 0.61 [0.55-0.67]).There was high coverage among health workers (OR 9.84 [8.79-11.02] and care workers (OR4.17 [3.20-5.43]) compared to non-key workers, but lower in hospitality and retail workers(OR 0.73 [0.64-0.82] and 0.77 [0.70-0.85] respectively) after adjusting for age and keycovariates.

Working paper

Riley S, Eales O, Haw D, Wang H, Walters C, Ainslie K, Christina A, Fronterre C, Diggle P, Ashby D, Donnelly C, Barclay W, Cooke G, Ward H, Darzi A, Elliott Pet al., 2021, REACT-1 round 13 interim report: acceleration of SARS-CoV-2 Delta epidemic in the community in England during late June and early July 2021

BackgroundDespite high levels of vaccination in the adult population, cases of COVID-19 have risenexponentially in England since the start of May 2021 driven by the Delta variant. However,with far fewer hospitalisations and deaths per case during the recent growth in casescompared with 2020, it is intended that all remaining social distancing legislation in Englandwill be removed from 19 July 2021.MethodsWe report interim results from round 13 of the REal-time Assessment of CommunityTransmission-1 (REACT-1) study in which a cross-sectional sample of the population ofEngland was asked to provide a throat and nose swab for RT-PCR and to answer aquestionnaire. Data collection for this report (round 13 interim) was from 24 June to 5 July2021.ResultsIn round 13 interim, we found 237 positives from 47,729 swabs giving a weighted prevalenceof 0.59% (0.51%, 0.68%) which was approximately four-fold higher compared with round 12at 0.15% (0.12%, 0.18%). This resulted from continued exponential growth in prevalencewith an average doubling time of 15 (13, 17) days between round 12 and round 13.However, during the recent period of round 13 interim only, we observed a shorter doublingtime of 6.1 (4.0, 12) days with a corresponding R number of 1.87 (1.40, 2.45). There weresubstantial increases in all age groups under the age of 75 years, and especially at youngerages, with the highest prevalence in 13 to 17 year olds at 1.33% (0.97%, 1.82%) and in 18 to24 years olds at 1.40% (0.89%, 2.18%). Infections have increased in all regions with thelargest increase in London where prevalence increased more than eight-fold from 0.13%(0.08%, 0.20%) in round 12 to 1.08% (0.79%, 1.47%) in round 13 interim. Overall,prevalence was over 3 times higher in the unvaccinated compared with those reporting twodoses of vaccine in both round 12 and round 13 interim, although there was a similarproportional increase in prevalence in vaccinated and unvaccinated individuals between thetwo rounds.DiscussionWe

Working paper

Alexander J, Powell N, 2021, SARS-CoV-2 vaccination in immunosuppressed patients with inflammatory bowel disease: should our approach change?, The Lancet Gastroenterology and Hepatology, Vol: 6, Pages: 528-529, ISSN: 2468-1253

Journal article

Lazarus J, Picchio C, Byrne C, Crespo J, Colombo M, Cooke G, Dore G, Grebely J, Ward J, White T, Dillon Jet al., 2021, A global systematic review of efforts to accelerate the elimination of hepatitis C virus (HCV) through micro-elimination, Publisher: ELSEVIER, Pages: S661-S662, ISSN: 0168-8278

Conference paper

Drake TM, Fairfield CJ, Pius R, Knight SR, Norman L, Girvan M, Hardwick HE, Docherty AB, Thwaites RS, Openshaw PJM, Baillie JK, Harrison EM, Semple MG, ISARIC4C Investigatorset al., 2021, Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study, The Lancet Rheumatology, Vol: 3, Pages: e498-e506, ISSN: 2665-9913

Background: Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease. Methods: This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations. Results: Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no si

Journal article

Lemoine M, Cooke GS, Thursz M, Matthews PCet al., 2021, Cuts to UK official development assistance budget jeopardise global viral hepatitis elimination goals., Lancet Gastroenterol Hepatol, Vol: 6, Pages: 527-528

Journal article

Adekoya I, Maraj D, Steiner L, Yaphe H, Moja L, Magrini N, Cooke G, Loeb M, Persaud Net al., 2021, Comparison of antibiotics included in national essential medicines lists of 138 countries using the WHO Access, Watch, Reserve (AWaRe) classification: a cross-sectional study, The Lancet Infectious Diseases, ISSN: 1473-3099

BackgroundThe WHO Model List of Essential Medicines classified antibiotics into Access, Watch, and Reserve (AWaRe) categories for the treatment of 31 priority bacterial infections as a tool to facilitate antibiotic stewardship and optimal use. We compared the listing of antibiotics on national essential medicines lists (NEMLs) to those in the 2019 WHO Model List and the AWaRe classification database to determine the degree to which NEMLs are in alignment with the AWaRe classification framework recommended by WHO.MethodsIn this cross-sectional study, we obtained up-to-date (data after 2017) NEMLs from our Global Essential Medicines (GEM) database, WHO online resources, and individual countries' websites. From the 2019 WHO Model List we extracted, as a reference standard, a list of 37 antibiotics (44 unique antibiotics after accounting for combination drugs or therapeutically equivalent drugs as specified by WHO) that were considered essential in treating 31 of the most common and severe clinical infectious syndromes (priority infections). From the WHO AWaRe Classification Database, which contains commonly used antibiotics globally, we extracted a list of 122 AWaRe antibiotics listed by at least one country in the GEM database. We then assessed individual countries' NEMLs for listing of the 44 essential and 122 commonly used antibiotics, overall and according to AWaRe classification group. We also evaluated and summarised the listing of both first-choice and second-choice treatments for the 31 priority infections. A total coverage score was calculated for each country by assigning a treatment score of 0–3 for each priority infection on the basis of whether first-choice and second-choice treatments, according to the 2019 WHO Model List, were included in the country's NEML. Coverage scores were then compared against the score of the 2019 WHO Model List and across World Bank income groups and WHO regions.FindingsAs of July 7, 2020, we had up-to-date NEMLs for 138 c

Journal article

Bloom CI, Drake TM, Docherty AB, Lipworth BJ, Johnston SL, Nguyen-Van-Tam JS, Carson G, Dunning J, Harrison EM, Baillie JK, Semple MG, Cullinan P, Openshaw PJM, Alex B, Bach B, Barclay WS, Bogaert D, Chand M, Cooke GS, Filipe AD, Fletcher T, Green CA, Harrison EM, Hiscox JA, Ho AY, Horby PW, Ijaz S, Khoo S, Klenerman P, Law A, Lim WS, Mentzer AJ, Merson L, Meynert AM, Noursadeghi M, Moore SC, Palmarini M, Paxton WA, Pollakis G, Price N, Rambaut A, Robertson DL, Russell CD, Sancho-Shimizu V, Scott JT, Silva TD, Sigfrid L, Solomon T, Sriskandan S, Stuart D, Summers C, Tedder RS, Thomson EC, Thompson AAR, Thwaites RS, Turtle LCW, Zambon M, Hardwick H, Donohue C, Lyons R, Griffiths F, Oosthuyzen W, Norman L, Pius R, Fairfield CJ, Knight SR, Mclean KA, Murphy D, Shaw CA, Dalton J, Girvan M, Saviciute E, Roberts S, Harrison J, Marsh L, Connor M, Halpin S, Jackson C, Gamble C, Leeming G, Law A, Wham M, Clohisey S, Hendry R, Scott-Brown J, Greenhalf W, Shaw V, McDonald S, Keating S, Ahmed KA, Armstrong JA, Ashworth M, Asiimwe IG, Bakshi S, Barlow SL, Booth L, Brennan B, Bullock K, Catterall BWA, Clark JJ, Clarke EA, Cole S, Cooper L, Cox H, Davis C, Dincarslan O, Dunn C, Dyer P, Elliott A, Evans A, Finch L, Fisher LWS, Foster T, Garcia-Dorival I, Greenhalf W, Gunning P, Hartley C, Jensen RL, Jones CB, Jones TR, Khandaker S, King K, Kiy RT, Koukorava C, Lake A, Lant S, Latawiec D, Lavelle-Langham L, Lefteri D, Lett L, Livoti LA, Mancini M, McDonald S, McEvoy L, McLauchlan J, Metelmann S, Miah NS, Middleton J, Mitchell J, Moore SC, Murphy EG, Penrice-Randal R, Pilgrim J, Prince T, Reynolds W, Ridley PM, Sales D, Shaw VE, Shears RK, Small B, Subramaniam KS, Szemiel A, Taggart A, Tanianis-Hughes J, Thomas J, Trochu E, Tonder LV, Wilcock E, Zhang JE, Flaherty L, Maziere N, Cass E, Carracedo AD, Carlucci N, Holmes A, Massey H, Adeniji K, Agranoff D, Agwuh K, Ail D, Alegria A, Angus B, Ashish A, Atkinson D, Bari S, Barlow G, Barnass S, Barrett N, Bassford C, Baxter D, Beadsworth Met al., 2021, Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK, The Lancet Respiratory Medicine, Vol: 9, Pages: 699-711, ISSN: 2213-2600

BackgroundStudies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use.MethodsWe analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16–49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma.Findings75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16–49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16–49 years: adjusted odds ratio [OR] 1·20 [95% CI

Journal article

Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott Pet al., 2021, Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people

IntroductionLong COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorlydefined syndrome. There is uncertainty about its predisposing factors and the extent of theresultant public health burden, with estimates of prevalence and duration varying widely.MethodsWithin rounds 3–5 of the REACT-2 study, 508,707 people in the community in England wereasked about a prior history of COVID-19 and the presence and duration of 29 differentsymptoms. We used uni- and multivariable models to identify predictors of persistence ofsymptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12weeks, and used unsupervised learning to cluster individuals by symptoms experienced.ResultsAmong the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2%(95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at leastone symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. Thisgives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people 8,771/28,713 (30.5%)with at least one symptom lasting 12 weeks or more reported having had severe COVID-19symptoms (“significant effect on my daily life”) at the time of their illness, giving a weightedprevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptomswas higher in women than men (OR: 1.51 [1.46,1.55]) and, conditional on reporting symptoms,risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade oflife. Obesity, smoking or vaping, hospitalisation , and deprivation were also associated with ahigher probability of persistent symptoms, while Asian ethnicity was associated with a lowerprobability. Two stable clusters were identified based on symptoms that persisted for 12 weeks ormore: in the largest cluster, tiredness predominated

Working paper

Davies B, Araghi M, Moshe M, Gao H, Bennet K, Jenkins J, Atchison C, Darzi A, Ashby D, Riley S, Barclay W, Elliott P, Ward H, Cooke Get al., 2021, Acceptability, usability and performance of lateral flow immunoassay tests for SARSCoV-2 antibodies: REACT-2 study of self-testing in non-healthcare key workers, Publisher: Cold Spring Harbor Laboratory

BackgroundSeroprevalence studies in key worker populations are essential to understand the epidemiology of SARS-CoV-2. Various technologies, including laboratory assays and pointof-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.MethodsIn June 2020, current and former members of the UK Police forces and Fire service performed a self-test lateral flow immunoassay (LFIA) and provided a saliva sample, nasopharyngeal swab, venous blood samples for Abbott ELISA and had a nurse performed LFIA. We present the prevalence of PCR positivity and antibodies to SARS-CoV-2 in this cohort following the first wave of infection in England; the acceptability and usability of selftest LFIAs (defined as use of the LFIA kit and provision of a valid result, respectively); and determine the sensitivity and specificity of LFIAs compared to laboratory ELISAs.ResultsIn this cohort of non-healthcare key workers, 7.4% (396/5,348; 95% CI, 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (6.9-11.4) in those under 40 years, 11.5% (8.8-15.0) in those of non-white British ethnicity and 7.8% (7.1-8.7) in those currently working.The self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 0.77-0.83). The LFIAs (self-test and nurse-performed) had a similar performance: compared to ELISA, sensitivity was 82.1% (77.7-86.0) self-test and 76.4% (71.9-80.5) nurse-performed with specificity of 97.8% (97.3-98.2) and 98.5% (98.1-98.8) respectively.ConclusionA greater proportion of the non-healthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (5.8-6.1) following the first wave in England. The high acceptability and usability reported by participants and the similar performance of self-test and nurse-performed LFIAs indicate that t

Working paper

Riley S, Wang H, Eales O, Haw D, Walters C, Ainslie K, Atchison C, Fronterre C, Diggle P, Page A, Prosolek S, Trotter AJ, Le Viet T, Alikhan N-F, The COVID-19 Genomics UK Consortium COG-UK, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2021, REACT-1 round 12 report: resurgence of SARS-CoV-2 infections in England associated with increased frequency of the Delta variant

BackgroundEngland entered a third national lockdown from 6 January 2021 due to the COVID-19pandemic. Despite a successful vaccine rollout during the first half of 2021, cases andhospitalisations have started to increase since the end of May as the SARS-CoV-2 Delta(B.1.617.2) variant increases in frequency. The final step of relaxation of COVID-19restrictions in England has been delayed from 21 June to 19 July 2021.MethodsThe REal-time Assessment of Community Transmision-1 (REACT-1) study measures theprevalence of swab-positivity among random samples of the population of England. Round12 of REACT-1 obtained self-administered swab collections from participants from 20 May2021 to 7 June 2021; results are compared with those for round 11, in which swabs werecollected from 15 April to 3 May 2021.ResultsBetween rounds 11 and 12, national prevalence increased from 0.10% (0.08%, 0.13%) to0.15% (0.12%, 0.18%). During round 12, we detected exponential growth with a doublingtime of 11 (7.1, 23) days and an R number of 1.44 (1.20, 1.73). The highest prevalence wasfound in the North West at 0.26% (0.16%, 0.41%) compared to 0.05% (0.02%, 0.12%) in theSouth West. In the North West, the locations of positive samples suggested a cluster inGreater Manchester and the east Lancashire area. Prevalence in those aged 5-49 was 2.5times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at0.08% (0.06%, 0.11%). At the beginning of February 2021, the link between infection ratesand hospitalisations and deaths started to weaken, although in late April 2021, infectionrates and hospital admissions started to reconverge. When split by age, the weakened linkbetween infection rates and hospitalisations at ages 65 years and above was maintained,while the trends converged below the age of 65 years. The majority of the infections in theyounger group occurred in the unvaccinated population or those without a stated vaccinehistory. We observed the rapid replacement of the Alpha (

Working paper

Leclerc QJ, Fuller NM, Keogh RH, Diaz-Ordaz K, Sekula R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Atkins KE, Procter SR, Knight GMet al., 2021, Importance of patient bed pathways and length of stay differences in predicting COVID-19 hospital bed occupancy in England., BMC Health Services Research, Vol: 21, Pages: 1-15, ISSN: 1472-6963

BACKGROUND: Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient's "bed pathway" - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy. METHODS: We obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020. RESULTS: In both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: "Ward, CC, Ward", "Ward, CC", "CC" and "CC, Ward". Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days. For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities. CONCLUSIONS: We identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occ

Journal article

Riley S, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2021, Resurgence of SARS-CoV-2: detection by community viral surveillance, Science, Vol: 372, Pages: 990-995, ISSN: 0036-8075

Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has mainly relied on case reporting, which is biased by health service performance, test availability, and test-seeking behaviors. We report a community-wide national representative surveillance program in England based on self-administered swab results from ~594,000 individuals tested for SARS-CoV-2, regardless of symptoms, between May and the beginning of September 2020. The epidemic declined between May and July 2020 but then increased gradually from mid-August, accelerating into early September 2020 at the start of the second wave. When compared with cases detected through routine surveillance, we report here a longer period of decline and a younger age distribution. Representative community sampling for SARS-CoV-2 can substantially improve situational awareness and feed into the public health response even at low prevalence.

Journal article

Li HK, Kaforou M, Rodriguez-Manzano J, Channon-Wells S, Monir A, Habgood-Coote D, Gupta RK, Mills EA, Lin J, Chiu Y-H, Pennisi I, Miglietta L, Mehta R, Obaray N, Herberg JA, Wright VJ, Georgiou P, Shallcross LJ, Mentzer AJ, Levin M, Cooke GS, Noursadeghi M, Sriskandan Set al., 2021, Discovery and validation of a 3-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations; a case-control then observational cohort study, The Lancet Microbe, ISSN: 2666-5247

Background: Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We sought to derive and validate a blood transcriptional signature to detect viral infections including COVID-19 among adults with suspected infection presenting to the Emergency Department (ED).Methods: Blood RNA sequencing was performed on a discovery cohort of adults attending the ED with suspected infection who had subsequently-confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes were subjected to feature selection to derive the most parsimonious discriminating signature. RT-qPCR validation of the signature was then performed in a prospective cohort of ED patients presenting with undifferentiated fever, and a second case-control cohort of ED patients with COVID-19 or bacterial infection. Signature performance was assessed by calculating area under receiver-operating characteristic curves (AUC-ROCs), sensitivities, and specificities.Findings: A 3-gene transcript signature was derived from the discovery cohort of 56 bacterial and 27 viral infection cases. In the validation cohort of 200 cases, the signature differentiated bacterial from viral infections with an AUC-ROC of 0.976 (95% CI: 0.919-1.000), sensitivity 97.3% and specificity of 100%. The AUC-ROC for C-reactive protein (CRP) and leucocyte count (WCC) was 0.833 (95% CI: 0.694-0.944) and 0.938 (95% CI: 0.840-0.986) respectively. The signature achieved higher net benefit in decision curve analysis than either CRP or WCC for discriminating viral infections from all other cases. In the second validation analysis the signature discriminated 35 bacterial infections from 34 SARS-CoV-2 positive COVID-19 infections with AUC-ROC of 0.953 (95% CI: 0.893-0.992), sensitivity 88.6% and specificity of 94.1%.Interpretation: This novel 3-gene signature discriminates viral i

Journal article

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