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• Journal article
  Openshaw PJM, 2022,

  Using correlates to accelerate vaccinology.

  , Science, Vol: 375, Pages: 22-23, ISSN: 0036-8075
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• Journal article
  David A, Parkinson N, Peacock TP, Pairo-Castineira E, Khanna T, Cobat A, Tenesa A, Sancho-Shimizu V, Casanova J-L, Abel L, Barclay WS, Baillie JK, Sternberg MJEet al., 2022,

  A common TMPRSS2 variant has a protective effect against severe COVID-19

  , Current Research in Translational Medicine, Vol: 70, ISSN: 2452-3186

  Background: The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus’ spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring TMPRSS2 human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection.Methods: We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760 C>T, p.V160M), which has a minor allele frequency ranging from from 0.14 in Ashkenazi Jewish to 0.38 in East Asians. We analysed the association between the rs12329760 and COVID-19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2V160M). A SARS-CoV-2 pseudovirus entry assay was used to investigate the ability of TMPRSS2V160M to promote viral entry.Results: We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID-19 (OR 0.87, 95%CI:0.79-0.97, p=0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p=1.3 × 10−3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, affects the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells.Conclusion: TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID-19. Further studies are needed to assess the expression of TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for

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• Journal article
  Lalvani A, Hakki S, Singanayagam A, Dunning J, Barnett JL, Crone MA, Freemont PS, Ferguson NMet al., 2022,

  Transmissibility of SARS-CoV-2 among fully vaccinated individuals reply

  , LANCET INFECTIOUS DISEASES, Vol: 22, Pages: 18-19, ISSN: 1473-3099
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  • Citations: 1
• Journal article
  Dowell AC, Butler MS, Jinks E, Tut G, Lancaster T, Sylla P, Begum J, Bruton R, Pearce H, Verma K, Logan N, Tyson G, Spalkova E, Margielewska-Davies S, Taylor GS, Syrimi E, Baawuah F, Beckmann J, Okike I, Ahmad S, Garstang J, Brent AJ, Brent B, Ireland G, Aiano F, Amin-Chowdhury Z, Jones S, Borrow R, Linley E, Wright J, Azad R, Waiblinger D, Davis C, Thomson E, Palmarini M, Willett BJ, Barclay WS, Poh J, Amirthalingam G, Brown KE, Ramsay ME, Zuo J, Moss P, Ladhani Set al., 2022,

  Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection

  , NATURE IMMUNOLOGY, Vol: 23, Pages: 40-+, ISSN: 1529-2908
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  • Citations: 91
• Journal article
  McCrone JT, Hill V, Bajaj S, Pena RE, Lambert BC, Inward R, Bhatt S, Volz E, Ruis C, Dellicour S, Baele G, Zarebski AE, Sadilek A, Wu N, Schneider A, Ji X, Raghwani J, Jackson B, Colquhoun R, O'Toole Á, Peacock TP, Twohig K, Thelwall S, Dabrera G, Myers R, COVID-19 genomics UK COG-UK consortium, Faria NR, Huber C, Bogoch II, Khan K, du Plessis L, Barrett JC, Aanensen DM, Barclay WS, Chand M, Connor T, Loman NJ, Suchard MA, Pybus OG, Rambaut A, Kraemer MUGet al., 2021,

  Context-specific emergence and growth of the SARS-CoV-2 Delta variant.

  , medRxiv

  The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases 1-3 . The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions 4,5 . Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

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• Journal article
  Knight SR, Gupta RK, Ho A, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Olliaro PL, Pritchard MG, Russell CD, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann O, Turtle LCW, Openshaw PJM, Baillie JK, Docherty A, Semple MG, Noursadeghi M, Harrison EMet al., 2021,

  Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol

  , Thorax, Vol: 77, Pages: 1-10, ISSN: 0040-6376

  Purpose To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19.Methods Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups.Results 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, –0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions.Conclusion Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making.Trial registration number ISRCTN66726260.

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• Journal article
  Mlcochova P, Kemp SA, Dhar MS, Papa G, Meng B, Ferreira IATM, Datir R, Collier DA, Albecka A, Singh S, Pandey R, Brown J, Zhou J, Goonawardane N, Mishra S, Whittaker C, Mellan T, Marwal R, Datta M, Sengupta S, Ponnusamy K, Radhakrishnan VS, Abdullahi A, Charles O, Chattopadhyay P, Devi P, Caputo D, Peacock T, Wattal C, Goel N, Satwik A, Vaishya R, Agarwal M, Chauhan H, Chauhan H, Dikid T, Gogia H, Lall H, Verma K, Dhar MS, Singh MK, Soni N, Meena N, Madan P, Singh P, Sharma R, Sharma R, Kabra S, Kumar S, Kumari S, Sharma U, Chaudhary U, Sivasubbu S, Scaria V, Oberoi JK, Raveendran R, Datta S, Das S, Maitra A, Chinnaswamy S, Biswas NK, Parida A, Raghav SK, Prasad P, Sarin A, Mayor S, Ramakrishnan U, Palakodeti D, Seshasayee ASN, Thangaraj K, Bashyam MD, Dalal A, Bhat M, Shouche Y, Pillai A, Abraham P, Potdar VA, Cherian SS, Desai AS, Pattabiraman C, Manjunatha MV, Mani RS, Udupi GA, Nandicoori V, Tallapaka KB, Sowpati DT, Kawabata R, Kawabata R, Morizako N, Sadamasu K, Asakura H, Nagashima M, Yoshimura K, Ito J, Kimura I, Uriu K, Kosugi Y, Suganami M, Oide A, Yokoyama M, Chiba M, Saito A, Butlertanaka EP, Tanaka YL, Ikeda T, Motozono C, Nasser H, Shimizu R, Yuan Y, Kitazato K, Hasebe H, Nakagawa S, Wu J, Takahashi M, Fukuhara T, Shimizu K, Tsushima K, Kubo H, Shirakawa K, Kazuma Y, Nomura R, Horisawa Y, Takaori-Kondo A, Tokunaga K, Ozono S, Baker S, Baker S, Dougan G, Hess C, Kingston N, Lehner PJ, Lyons PA, Matheson NJ, Owehand WH, Saunders C, Summers C, Thaventhiran JED, Toshner M, Weekes MP, Maxwell P, Shaw A, Bucke A, Calder J, Canna L, Domingo J, Elmer A, Fuller S, Harris J, Hewitt S, Kennet J, Jose S, Kourampa J, Meadows A, O'Brien C, Price J, Publico C, Rastall R, Ribeiro C, Rowlands J, Ruffolo V, Tordesillas H, Bullman B, Dunmore BJ, Fawke S, Graf S, Hodgson J, Huang C, Hunter K, Jones E, Legchenko E, Matara C, Martin J, Mescia F, O'Donnell C, Pointon L, Pond N, Shih J, Sutcliffe R, Tilly T, Treacy C, Tong Z, Wood J, Wylot M, Bergamaschi L, Betancourt A, Boweet al., 2021,

  SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

  , NATURE, Vol: 599, Pages: 114-+, ISSN: 0028-0836
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  • Citations: 625
• 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, The COVID-19 Genomics UK Consortium COG-UK, Ashby D, Donnelly C, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley Set al., 2021,

  Exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant

  , Science, Vol: 374, Pages: 1-11, ISSN: 0036-8075

  SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

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• Conference paper
  Fries A, Mandagere V, Parker R, Tolosa-Wright M, Berrocal-Almanza L, Hoang L, Boakye A, Halliday A, Lalvani Aet al., 2021,

  EVALUATION OF MYCOBACTERIUM TUBERCULOSIS-SPECIFIC IFN-G, TNF-A, CXCL10, IL2, CCL2, CCL7 AND CCL4 LEVELS FOR ACTIVE TUBERCULOSIS DIAGNOSIS

  , Publisher: BMJ PUBLISHING GROUP, Pages: A27-A28, ISSN: 0040-6376
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• Journal article
  Wickenhagen A, Sugrue E, Lytras S, Kuchi S, Noerenberg M, Turnbull ML, Loney C, Herder V, Allan J, Jarmson I, Cameron-Ruiz N, Varjak M, Pinto RM, Lee JY, Iselin L, Palmalux N, Stewart DG, Swingler S, Greenwood EJD, Crozier TWM, Gu Q, Davies EL, Clohisey S, Wang B, Maranhao Costa FT, Santana MF, de Lima Ferreira LC, Murphy L, Fawkes A, Meynert A, Grimes G, Filho JLDS, Marti M, Hughes J, Stanton RJ, Wang ECY, Ho A, Davis I, Jarrett RF, Castello A, Robertson DL, Semple MG, Openshaw PJM, Palmarini M, Lehner PJ, Baillie JK, Rihn SJ, Wilson SJet al., 2021,

  A prenylated dsRNA sensor protects against severe COVID-19

  , Science, Vol: 374, Pages: 1-18, ISSN: 0036-8075
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