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• Journal article
  Halliday A, Jain P, Hoang L, Parker R, Tolosa-Wright M, Masonou T, Green N, Boakye A, Takwoingi Y, Hamilton S, Mandagere V, Fries A, Coin L, Deeks J, White PJ, Levin M, Beverley P, Kon OM, Lalvani Aet al., 2021,

  New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study

  , Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-160, ISSN: 2050-4365

  <jats:sec id="abs1-1"> <jats:title>Background</jats:title> <jats:p>Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed.</jats:p> </jats:sec> <jats:sec id="abs1-2"> <jats:title>Objective</jats:title> <jats:p>To validate promising new technologies [namely whole-blood transcriptomics, proteomics, flow cytometry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)] and existing signatures for the detection of active TB in samples obtained from individuals with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-3"> <jats:title>Design</jats:title> <jats:p>Four substudies, each of which used samples from the biobank collected as part of the interferon gamma release assay (IGRA) in the Diagnostic Evaluation of Active TB study, which was a prospective cohort of patients recruited with suspected TB.</jats:p> </jats:sec> <jats:sec id="abs1-4"> <jats:title>Setting</jats:title> <jats:p>Secondary care.</jats:p> </jats:sec> <jats:sec id="abs1-5"> <jats:title>Participants</jats:title> <jats:p>Adults aged ≥ 16 years presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham, with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-6"> <jats:title>Interventions</jats:title> <jats:p>New tests using genome-wide gene expression microarray

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• Journal article
  Townsend A, Rijal P, Xiao J, Tan TK, Huang K-YA, Schimanski L, Huo J, Gupta N, Rahikainen R, Matthews PC, Crook D, Hoosdally S, Dunachie S, Barnes E, Street T, Conlon CP, Frater J, Arancibia-Carcamo CV, Rudkin J, Stoesser N, Karpe F, Neville M, Ploeg R, Oliveira M, Roberts DJ, Lamikanra AA, Tsang HP, Bown A, Vipond R, Mentzer AJ, Knight JC, Kwok AJ, Screaton GR, Mongkolsapaya J, Dejnirattisai W, Supasa P, Klenerman P, Dold C, Baillie JK, Moore SC, Openshaw PJM, Semple MG, Turtle LCW, Ainsworth M, Allcock A, Beer S, Bibi S, Skelly D, Stafford L, Jeffrey K, O'Donnell D, Clutterbuck E, Espinosa A, Mendoza M, Georgiou D, Lockett T, Martinez J, Perez E, Sanchez VG, Scozzafava G, Sobrinodiaz A, Thraves H, Joly Eet al., 2021,

  A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

  , NATURE COMMUNICATIONS, Vol: 12
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  • Citations: 38
• Journal article
  Yates T, Zaccardi F, Islam N, Razieh C, Gillies CL, Lawson CA, Chudasama Y, Rowlands A, Davies MJ, Docherty AB, Openshaw PJ, Baillie JK, Semple MG, ISARIC4C investigators, Khunti Ket al., 2021,

  Obesity, ethnicity and risk of critical care, mechanical ventilation and mortality in patients admitted to hospital with COVID-19: Analysis of the ISARIC CCP-UK cohort.

  , Obesity (Silver Spring, Md.), Vol: 29, Pages: 1223-1230, ISSN: 1071-7323

  OBJECTIVE: To investigate the association of obesity with in-hospital COVID-19 outcomes in different ethnic groups. METHODS: Patients admitted to hospital with COVID-19 in the United Kingdom through the Clinical Characterisation Protocol UK (CCP-UK) developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) were included from 6th February to 12th October 2020. Ethnicity was classified as: white, South Asian, black and other minority ethnic groups. Outcomes were admission to critical care, mechanical ventilation and in-hospital mortality, adjusted for age, sex and chronic diseases. RESULTS: 54,254 (age = 76 years; 45.0% women) white, 3,728 (57 years; 41.1%) South Asian, 2,523 (58 years; 44.9%) black and 5,427 (61 years; 40.8%) other ethnicities were included. Obesity was associated with all outcomes in all ethnic groups, with associations strongest for black ethnicities. When stratified by ethnicity and obesity status, the OR for admission to critical care, mechanical ventilation and mortality in black ethnicities with obesity were 3.91 (3.13, 4.88), 5.03 (3.94, 6.63), 1.93 (1.49, 2.51) respectively, compared to white ethnicities without obesity. CONCLUSIONS: Obesity was associated with an elevated risk of in-hospital COVID-19 outcomes in all ethnic groups, with associations strongest in black ethnicities.

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• Journal article
  Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, Liew F, Russell CD, Moore SC, Fairfield C, Carter E, Abrams S, Short C, Thaventhiran T, Bergstrom E, Gardener Z, Ascough S, Chiu C, Docherty AB, Hunt D, Crow YJ, Solomon T, Taylor GP, Turtle L, Harrison EM, Dunning J, Semple MG, Baillie JK, Openshaw PJMet al., 2021,

  Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19

  , Science Immunology, Vol: 6, Pages: 1-17, ISSN: 2470-9468

  While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.

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• Journal article
  Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, Walker S, Parkinson N, Fourman MH, Russell CD, Furniss J, Richmond A, Gountouna E, Wrobel N, Harrison D, Wang B, Wu Y, Meynert A, Griffiths F, Oosthuyzen W, Kousathanas A, Moutsianas L, Yang Z, Zhai R, Zheng C, Grimes G, Beale R, Millar J, Shih B, Keating S, Zechner M, Haley C, Porteous DJ, Hayward C, Yang J, Knight J, Summers C, Shankar-Hari M, Klenerman P, Turtle L, Ho A, Moore SC, Hinds C, Horby P, Nichol A, Maslove D, Ling L, McAuley D, Montgomery H, Walsh T, Pereira A, Renieri A, GenOMICC Investigators, ISARICC Investigators, COVID-19 Human Genetics Initiative, 23andMe Investigators, BRACOVID Investigators, Gen-COVID Investigators, Shen X, Ponting CP, Fawkes A, Tenesa A, Caulfield M, Scott R, Rowan K, Murphy L, Openshaw PJM, Semple MG, Law A, Vitart V, Wilson JF, Baillie JKet al., 2021,

  Genetic mechanisms of critical illness in Covid-19

  , Nature, Vol: 591, Pages: 92-98, ISSN: 0028-0836

  Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice.

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• Journal article
  Thomson EC, Rosen LE, Shepherd JG, Spreafico R, Filipe ADS, Wojcechowskyj JA, Davis C, Piccoli L, Pascall DJ, Dillen J, Lytras S, Czudnochowski N, Shah R, Meury M, Jesudason N, De Marco A, Li K, Bassi J, O'Toole A, Pinto D, Colquhoun RM, Culap K, Jackson B, Zatta F, Rambaut A, Jaconi S, Sreenu VB, Nix J, Zhang I, Jarrett RF, Glass WG, Beltramello M, Nomikou K, Pizzuto M, Tong L, Cameroni E, Croll T, Johnson N, Di Iulio J, Wickenhagen A, Ceschi A, Harbison AM, Mair D, Ferrari P, Smollett K, Sallusto F, Carmichael S, Garzoni C, Nichols J, Galli M, Hughes J, Riva A, Ho A, Schiuma M, Semple MG, Openshaw PJM, Fadda E, Baillie JK, Chodera JD, Rihn SJ, Lycett SJ, Virgin HW, Telenti A, Corti D, Robertson DL, Snell Get al., 2021,

  Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity

  , CELL, Vol: 184, Pages: 1171-+, ISSN: 0092-8674
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  • Citations: 359
• Journal article
  Hoang LT, Jain P, Pillay TD, Tolosa-Wright M, Niazi U, Takwoingi Y, Halliday A, Berrocal-Almanza LC, Deeks JJ, Beverley P, Kon OM, Lalvani Aet al., 2021,

  Transcriptomic signatures for diagnosing tuberculosis in clinical practice: a prospective, multicentre cohort study

  , LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 366-375, ISSN: 1473-3099
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  • Citations: 16
• Journal article
  Quandelacy TM, Cummings DAT, Jiang CQ, Yang B, Kwok KO, Dai B, Shen R, Read JM, Zhu H, Guan Y, Riley S, Lessler Jet al., 2021,

  Using serological measures to estimate influenza incidence in the presence of secular trends in exposure and immuno-modulation of antibody response

  , INFLUENZA AND OTHER RESPIRATORY VIRUSES, Vol: 15, Pages: 235-244, ISSN: 1750-2640
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  • Citations: 2
• Journal article
  Nouvellet P, Bhatia S, Cori A, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, Eales O, van Elsland S, NASCIMENTO F, Fitzjohn R, Gaythorpe K, Geidelberg L, green W, Hamlet A, Hauck K, Hinsley W, Imai N, Jeffrey, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Nedjati Gilani G, Parag K, Pons Salort M, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Watson O, Whittaker C, Whittles L, Xi X, Ferguson N, Donnelly Cet al., 2021,

  Reduction in mobility and COVID-19 transmission

  , Nature Communications, Vol: 12, ISSN: 2041-1723

  In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts.Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world.Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation.In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

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  Ward H, Atchison C, Whitaker M, Ainslie KEC, Elliott J, Okell L, Redd R, Ashby D, Donnelly C, Barclay W, Darzi A, Cooke G, Riley S, Elliott Pet al., 2021,

  SARS-CoV-2 antibody prevalence in England following the first peak of the pandemic.

  , Nature Communications, Vol: 12, Pages: 1-8, ISSN: 2041-1723

  England has experienced a large outbreak of SARS-CoV-2, disproportionately affecting people from disadvantaged and ethnic minority communities. It is unclear how much of this excess is due to differences in exposure associated with structural inequalities. Here we report from the REal-time Assessment of Community Transmission-2 (REACT-2) national study of over 100,000 people. After adjusting for test characteristics and re-weighting to the population, overall antibody prevalence is 6.0% (95% CI: 5.8-6.1). An estimated 3.4 million people had developed antibodies to SARS-CoV-2 by mid-July 2020. Prevalence is two- to three-fold higher among health and care workers compared with non-essential workers, and in people of Black or South Asian than white ethnicity, while age- and sex-specific infection fatality ratios are similar across ethnicities. Our results indicate that higher hospitalisation and mortality from COVID-19 in minority ethnic groups may reflect higher rates of infection rather than differential experience of disease or care.

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