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
Authors: Eales Oliver , Page Andrew J. , de Oliveira Martins Leonardo , Wang Haowei , Bodinier Barbara , Haw David , Jonnerby Jakob , Atchison Christina ,   The COVID-19 Genomics UK (COG-UK) Consortium, Robson Samuel C. , Connor Thomas R. , Loman Nicholas J. , Golubchik Tanya , Nunez Rocio T. Martinez , Bonsall David , Rambaut Andrew , Snell Luke B. , Livett Rich , Ludden Catherine , Corden Sally , Nastouli Eleni , Nebbia Gaia , Johnston Ian , Lythgoe Katrina , Torok M. Estee , Goodfellow Ian G. , Prieto Jacqui A. , Saeed Kordo , Jackson David K. , Houlihan Catherine , Frampton Dan , Hamilton William L. , Witney Adam A. , Bucca Giselda , Pope Cassie F. , Moore Catherine , Thomson Emma C. , Harrison Ewan M. , Smith Colin P. , Rogan Fiona , Beckwith Shaun M. , Murray Abigail , Singleton Dawn , Eastick Kirstine , Sheridan Liz A. , Randell Paul , Jackson Leigh M. , Ariani Cristina V. , Gonçalves Sónia , Fairley Derek J. , Loose Matthew W. , Watkins Joanne , Moses Samuel , Nicholls Sam , Bull Matthew , Amato Roberto , Smith Darren L. , Aanensen David M. , Barrett Jeffrey C. , Aggarwal Dinesh , Shepherd James G. , Curran Martin D. , Parmar Surendra , Parker Matthew D. , Williams Catryn , Glaysher Sharon , Underwood Anthony P. , Bashton Matthew , Pacchiarini Nicole , Loveson Katie F. , Byott Matthew , Carabelli Alessandro M. , Templeton Kate E. , de Silva Thushan I. , Wang Dennis , Langford Cordelia F. , Sillitoe John , Gunson Rory N. , Cottrell Simon , O’Grady Justin , Kwiatkowski Dominic , Lillie Patrick J. , Cortes Nicholas , Moore Nathan , Thomas Claire , Burns Phillipa J. , Mahungu Tabitha W. , Liggett Steven , Beckett Angela H. , Holden Matthew T. G. , Levett Lisa J. , Osman Husam , Hassan-Ibrahim Mohammed O. , Simpson David A. , Chand Meera , Gupta Ravi K. , Darby Alistair C. , Paterson Steve , Pybus Oliver G. , Volz Erik M. , de Angelis Daniela , Robertson David L. , Martincorena Inigo , Aigrain Louise , Bassett Andrew R. , Wong Nick , Taha Yusri , Erkiert Michelle J. , Chapman Michael H. Spencer , Dewar Rebecca , McHugh Martin P. , Mookerjee Siddharth , Aplin Stephen , Harvey Matthew , Sass Thea , Umpleby Helen , Wheeler Helen , McKenna James P. , Warne Ben , Taylor Joshua F. , Chaudhry Yasmin , Izuagbe Rhys , Jahun Aminu S. , Young Gregory R. , McMurray Claire , McCann Clare M. , Nelson Andrew , Elliott Scott , Lowe Hannah , Price Anna , Crown Matthew R. , Rey Sara , Roy Sunando , Temperton Ben , Shaaban Sharif , Hesketh Andrew R. , Laing Kenneth G. , Monahan Irene M. , Heaney Judith , Pelosi Emanuela , Silviera Siona , Wilson-Davies Eleri , Fryer Helen , Adams Helen , du Plessis Louis , Johnson Rob , Harvey William T. , Hughes Joseph , Orton Richard J. , Spurgin Lewis G. , Bourgeois Yann , Ruis Chris , O’Toole Áine , Gourtovaia Marina , Sanderson Theo , Fraser Christophe , Edgeworth Jonathan , Breuer Judith , Michell Stephen L. , Todd John A. , John Michaela , Buck David , Gajee Kavitha , Kay Gemma L. , Peacock Sharon J. , Heyburn David , Kitchman Katie , McNally Alan , Pritchard David T. , Dervisevic Samir , Muir Peter , Robinson Esther , Vipond Barry B. , Ramadan Newara A. , Jeanes Christopher , Weldon Danni , Catalan Jana , Jones Neil , da Silva Filipe Ana , Williams Chris , Fuchs Marc , Miskelly Julia , Jeffries Aaron R. , Oliver Karen , Park Naomi R. , Ash Amy , Koshy Cherian , Barrow Magdalena , Buchan Sarah L. , Mantzouratou Anna , Clark Gemma , Holmes Christopher W. , Campbell Sharon , Davis Thomas , Tan Ngee Keong , Brown Julianne R. , Harris Kathryn A. , Kidd Stephen P. , Grant Paul R. , Xu-McCrae Li , Cox Alison , Madona Pinglawathee , Pond Marcus , Randell Paul A. , Withell Karen T. , Williams Cheryl , Graham Clive , Denton-Smith Rebecca , Swindells Emma , Turnbull Robyn , Sloan Tim J. , Bosworth Andrew , Hutchings Stephanie , Pymont Hannah M. , Casey Anna , Ratcliffe Liz , Jones Christopher R. , Knight Bridget A. , Haque Tanzina , Hart Jennifer , Irish-Tavares Dianne , Witele Eric , Mower Craig , Watson Louisa K. , Collins Jennifer , Eltringham Gary , Crudgington Dorian , Macklin Ben , Iturriza-Gomara Miren , Lucaci Anita O. , McClure Patrick C. , Carlile Matthew , Holmes Nadine , Moore Christopher , Storey Nathaniel , Rooke Stefan , Yebra Gonzalo , Craine Noel , Perry Malorie , Alikhan Nabil-Fareed , Bridgett Stephen , Cook Kate F. , Fearn Christopher , Goudarzi Salman , Lyons Ronan A. , Williams Thomas , Haldenby Sam T. , Durham Jillian , Leonard Steven , Davies Robert M. , Batra Rahul , Blane Beth , Spyer Moira J. , Smith Perminder , Yavus Mehmet , Williams Rachel J. , Mahanama Adhyana I. K. , Samaraweera Buddhini , Girgis Sophia T. , Hansford Samantha E. , Green Angie , Beaver Charlotte , Bellis Katherine L. , Dorman Matthew J. , Kay Sally , Prestwood Liam , Rajatileka Shavanthi , Quick Joshua , Poplawski Radoslaw , Reynolds Nicola , Mack Andrew , Morriss Arthur , Whalley Thomas , Patel Bindi , Georgana Iliana , Hosmillo Myra , Pinckert Malte L. , Stockton Joanne , Henderson John H. , Hollis Amy , Stanley William , Yew Wen C. , Myers Richard , Thornton Alicia , Adams Alexander , Annett Tara , Asad Hibo , Birchley Alec , Coombes Jason , Evans Johnathan M. , Fina Laia , Gatica-Wilcox Bree , Gilbert Lauren , Graham Lee , Hey Jessica , Hilvers Ember , Jones Sophie , Jones Hannah , Kumziene-Summerhayes Sara , McKerr Caoimhe , Powell Jessica , Pugh Georgia , Taylor Sarah , Trotter Alexander J. , Williams Charlotte A. , Kermack Leanne M. , Foulkes Benjamin H. , Gallis Marta , Hornsby Hailey R. , Louka Stavroula F. , Pohare Manoj , Wolverson Paige , Zhang Peijun , MacIntyre-Cockett George , Trebes Amy , Moll Robin J. , Ferguson Lynne , Goldstein Emily J. , Maclean Alasdair , Tomb Rachael , Starinskij Igor , Thomson Laura , Southgate Joel , Kraemer Moritz U. G. , Raghwani Jayna , Zarebski Alex E. , Boyd Olivia , Geidelberg Lily , Illingworth Chris J. , Jackson Chris , Pascall David , Vattipally Sreenu , Freeman Timothy M. , Hsu Sharon N. , Lindsey Benjamin B. , James Keith , Lewis Kevin , Tonkin-Hill Gerry , Tovar-Corona Jaime M. , Cox MacGregor , Abudahab Khalil , Menegazzo Mirko , MEng Ben E. W. Taylor , Yeats Corin A. , Mukaddas Afrida , Wright Derek W. , Colquhoun Rachel , Hill Verity , Jackson Ben , McCrone J. T. , Medd Nathan , Scher Emily , Keatley Jon-Paul , Curran Tanya , Morgan Sian , Maxwell Patrick , Smith Ken , Eldirdiri Sahar , Kenyon Anita , Holmes Alison H. , Price James R. , Wyatt Tim , Mather Alison E. , Skvortsov Timofey , Hartley John A. , Guest Martyn , Kitchen Christine , Merrick Ian , Munn Robert , Bertolusso Beatrice , Lynch Jessica , Vernet Gabrielle , Kirk Stuart , Wastnedge Elizabeth , Stanley Rachael , Idle Giles , Bradley Declan T. , Poyner Jennifer , Mori Matilde , Jones Owen , Wright Victoria , Brooks Ellena , Churcher Carol M. , Fragakis Mireille , Galai Katerina , Jermy Andrew , Judges Sarah , McManus Georgina M. , Smith Kim S. , Westwick Elaine , Attwood Stephen W. , Bolt Frances , Davies Alisha , De Lacy Elen , Downing Fatima , Edwards Sue , Meadows Lizzie , Jeremiah Sarah , Smith Nikki , Foulser Luke , Charalampous Themoula , Patel Amita , Berry Louise , Boswell Tim , Fleming Vicki M. , Howson-Wells Hannah C. , Joseph Amelia , Khakh Manjinder , Lister Michelle M. , Bird Paul W. , Fallon Karlie , Helmer Thomas , McMurray Claire L. , Odedra Mina , Shaw Jessica , Tang Julian W. , Willford Nicholas J. , Blakey Victoria , Raviprakash Veena , Sheriff Nicola , Williams Lesley-Anne , Feltwell Theresa , Bedford Luke , Cargill James S. , Hughes Warwick , Moore Jonathan , Stonehouse Susanne , Atkinson Laura , Lee Jack C. D. , Shah Divya , Alcolea-Medina Adela , Ohemeng-Kumi Natasha , Ramble John , Sehmi Jasveen , Williams Rebecca , Chatterton Wendy , Pusok Monika , Everson William , Castigador Anibolina , Macnaughton Emily , Bouzidi Kate El , Lampejo Temi , Sudhanva Malur , Breen Cassie , Sluga Graciela , Ahmad Shazaad S. Y. , George Ryan P. , Machin Nicholas W. , Binns Debbie , James Victoria , Blacow Rachel , Coupland Lindsay , Smith Louise , Barton Edward , Padgett Debra , Scott Garren , Cross Aidan , Mirfenderesky Mariyam , Greenaway Jane , Cole Kevin , Clarke Phillip , Duckworth Nichola , Walsh Sarah , Bicknell Kelly , Impey Robert , Wyllie Sarah , Hopes Richard , Bishop Chloe , Chalker Vicki , Harrison Ian , Gifford Laura , Molnar Zoltan , Auckland Cressida , Evans Cariad , Johnson Kate , Partridge David G. , Raza Mohammad , Baker Paul , Bonner Stephen , Essex Sarah , Murray Leanne J. , Lawton Andrew I. , Burton-Fanning Shirelle , Payne Brendan A. I. , Waugh Sheila , Gomes Andrea N. , Kimuli Maimuna , Murray Darren R. , Ashfield Paula , Dobie Donald , Ashford Fiona , Best Angus , Crawford Liam , Cumley Nicola , Mayhew Megan , Megram Oliver , Mirza Jeremy , Moles-Garcia Emma , Percival Benita , Driscoll Megan , Ensell Leah , Lowe Helen L. , Maftei Laurentiu , Mondani Matteo , Chaloner Nicola J. , Cogger Benjamin J. , Easton Lisa J. , Huckson Hannah , Lewis Jonathan , Lowdon Sarah , Malone Cassandra S. , Munemo Florence , Mutingwende Manasa , Nicodemi Roberto , Podplomyk Olga , Somassa Thomas , Beggs Andrew , Richter Alex , Cormie Claire , Dias Joana , Forrest Sally , Higginson Ellen E. , Maes Mailis , Young Jamie , Davidson Rose K. , Jackson Kathryn A. , Turtle Lance , Keeley Alexander J. , Ball Jonathan , Byaruhanga Timothy , Chappell Joseph G. , Dey Jayasree , Hill Jack D. , Park Emily J. , Fanaie Arezou , Hilson Rachel A. , Yaze Geraldine , Lo Stephanie , Afifi Safiah , Beer Robert , Maksimovic Joshua , McCluggage Kathryn , Spellman Karla , Bresner Catherine , Fuller William , Marchbank Angela , Workman Trudy , Shelest Ekaterina , Debebe Johnny , Sang Fei , Zamudio Marina Escalera , Francois Sarah , Gutierrez Bernardo , Vasylyeva Tetyana I. , Flaviani Flavia , Ragonnet-Cronin Manon , Smollett Katherine L. , Broos Alice , Mair Daniel , Nichols Jenna , Nomikou Kyriaki , Tong Lily , Tsatsani Ioulia , O’Brien Prof Sarah , Rushton Steven , Sanderson Roy , Perkins Jon , Cotton Seb , Gallagher Abbie , Allara Elias , Pearson Clare , Bibby David , Dabrera Gavin , Ellaby Nicholas , Gallagher Eileen , Hubb Jonathan , Lackenby Angie , Lee David , Manesis Nikos , Mbisa Tamyo , Platt Steven , Twohig Katherine A. , Morgan Mari , Aydin Alp , Baker David J. , Foster-Nyarko Ebenezer , Prosolek Sophie J. , Rudder Steven , Baxter Chris , Carvalho Sílvia F. , Lavin Deborah , Mariappan Arun , Radulescu Clara , Singh Aditi , Tang Miao , Morcrette Helen , Bayzid Nadua , Cotic Marius , Balcazar Carlos E. , Gallagher Michael D. , Maloney Daniel , Stanton Thomas D. , Williamson Kathleen A. , Manley Robin , Michelsen Michelle L. , Sambles Christine M. , Studholme David J. , Warwick-Dugdale Joanna , Eccles Richard , Gemmell Matthew , Gregory Richard , Hughes Margaret , Nelson Charlotte , Rainbow Lucille , Vamos Edith E. , Webster Hermione J. , Whitehead Mark , Wierzbicki Claudia , Angyal Adrienn , Green Luke R. , Whiteley Max , Betteridge Emma , Bronner Iraad F. , Farr Ben W. , Goodwin Scott , Lensing Stefanie V. , McCarthy Shane A. , Quail Michael A. , Rajan Diana , Redshaw Nicholas M. , Scott Carol , Shirley Lesley , Thurston Scott A. J. , Rowe Will , Gaskin Amy , Le-Viet Thanh , Bonfield James , Liddle Jennifier , Whitwham Andrew , Ashby Deborah , Barclay Wendy , Taylor Graham , Cooke Graham , Ward Helen , Darzi Ara , Riley Steven , Chadeau-Hyam Marc , Donnelly Christl A. , Elliott Paul 
Published: July 2022

Abstract
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.