Abstract

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 – 27.5] vs 47.6 days [45.5 – 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 – 36.8] vs 58.0 days [55.0 – 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Details

Title
Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab
Author
Lin Simeng 1   VIAFID ORCID Logo  ; Kennedy, Nicholas A 1   VIAFID ORCID Logo  ; Saifuddin Aamir 2   VIAFID ORCID Logo  ; Sandoval, Diana Muñoz 3   VIAFID ORCID Logo  ; Reynolds, Catherine J 3 ; Seoane, Rocio Castro 4 ; Kottoor, Sherine H 5 ; Pieper, Franziska P 3 ; Kai-Min, Lin 3 ; Butler, David K 3 ; Chanchlani Neil 1   VIAFID ORCID Logo  ; Nice, Rachel 6 ; Chee, Desmond 1 ; Bewshea Claire 7   VIAFID ORCID Logo  ; Janjua Malik 1 ; McDonald, Timothy J 8 ; Shaji, Sebastian 9   VIAFID ORCID Logo  ; Alexander, James L 10 ; Constable, Laura 5   VIAFID ORCID Logo  ; Lee, James C 11 ; Murray, Charles D 12 ; Hart, Ailsa L 13 ; Irving, Peter M 14 ; Jones Gareth-Rhys 15 ; Kok, Klaartje B 16 ; Lamb, Christopher A 17   VIAFID ORCID Logo  ; Lees, Charlie W 18   VIAFID ORCID Logo  ; Altmann, Daniel M 4 ; Boyton, Rosemary J 19   VIAFID ORCID Logo  ; Goodhand, James R 1   VIAFID ORCID Logo  ; Powell, Nick 10 ; Ahmad, Tariq 1   VIAFID ORCID Logo  ; Farjhana, Bokth 20 ; Cipriano Bessie 20 ; Francia, Caroline 20 ; Nosheen, Khalid 20 ; Khatun Hafiza 21 ; Kingston, Ashley 22 ; Irish, Lee 22 ; Lehmann Anouk 22 ; Naik Kinnari 22 ; Pabriaga Elise 20 ; Plaatjies Nicolene 20 ; Samuels, Kevin 20 ; Saich, Rebecca 23 ; Cousins, Hayley 23 ; Fraser, Wendy 23 ; Thomas, Rachel 23 ; Brown, Matthew 23 ; White, Benjamin 23 ; Kirkineziadis Nikolaos 23 ; Tilley, Bernadette 23 ; Rafeeq, Muhammed 24 ; Bi Rehana 24 ; Cotter, Catherine 24 ; Grove, Jayne 24 ; Hong, Kate 24 ; Howman, Ruth 24 ; Mitchell, Monica 24 ; Clayton, Sophie 24 ; Sultan Sugrah 24 ; Rooney, Melanie 24 ; Cottrill, Charlotte 24 ; Singh, Salil 25 ; Dawe, Chris 25 ; Hull, Robert 25 ; Silva, Natalie 25 ; Manning, Jonathan 26 ; Finlayson, Lauren 26 ; Roebuck, Allison 26 ; Dawson, Joy 26 ; Sonwalkar Sunil 27 ; Chambers, Naomi 27 ; Robinson, Matthew 27 ; Haigh, Andrew 27 ; Lear, Matapure 27 ; Raine, Tim 28 ; George, Varun 28 ; Kapizioni Christina 28 ; Strongili Konstantina 28 ; Thompson, Tina 28 ; Ahmed, Mohamed 28 ; Kontos Christos 28 ; Bourges Christophe 29 ; Barbutti Isabella 29 ; Gozzard, Megan E 29 ; Hendy, Philip 30 ; Bull Rhian 30 ; Costa, Patricia 30 ; Davey, Lisa 30 ; Hannington Hayley 30 ; Kribashnie, Nundlall 30 ; Martins Catarina 30 ; Avanzi, Laura 30 ; Carungcong Jaime 30 ; Barr, Sabrina 30 ; Appleby, Richard 30 ; Johnson, Emma 30 ; Phillis Kath 31 ; Gascoyne, Rachel 31 ; Crowder, Amanda 31 ; Whileman Amanda 31 ; London, Ian 32 ; Grounds, Jenny 32 ; Martin, Emmeline 32 ; Pajak Susie 32 ; Price, Jude 32 ; Cawley, Kathryn 32 ; Dhar Anjan 33 ; Brown, Ellen 33 ; Cowton Amanda 33 ; Stamp, Kimberley 33 ; Warner, Ben 34 ; Carmel, Stuart 34 ; Lacey, Louise 34 ; de Silva Shanika 35 ; Allcock, Clare 35 ; Harvey, Philip 35 ; Jones, Lesley 35 ; Cooke, Elise 35 ; Brooks, Johanne 36 ; Baker, Pearl 36 ; Beadle, Hannah 36 ; Cruz, Carina 36 ; Potter, Debbie 36 ; Collum, Joe 37 ; Masters Farzana 37 ; Kumar, Aashish 38 ; Coetzee, Samantha 38 ; Peiu Mihaela 38 ; Icke Becky 38 ; Raj, Meena 38 ; Gaynor, Edward 39 ; Chadokufa Sibongile 39 ; Huggett Bonita 39 ; Hamza, Meghari 39 ; El-Khouly, Sara 39 ; Fevronia, Kiparissi 39 ; Girshab Waffa 39 ; Claridge, Andrew 40 ; Fowler, Emily 40 ; McCafferty, Laura 40 ; Christodoulides Karolina 41 ; Clifford, Angela 41 ; Dawson, Patrick 41 ; Sailish, Honap 41 ; Lim, Samuel 41 ; Luber Raphael 41 ; Mahiouz Karina 41 ; Meade, Susanna 41 ; Parizade, Raymode 41 ; Reynolds, Rebecca 41 ; Stanton, Anna 41 ; Tripoli Sherill 41 ; Hare, Naomi 41 ; Balachandran Senthuran 41 ; North, Emma 41 ; North, Jessica 41 ; Browne Bria 41 ; Jameson, Ella 41 ; Siaw Yih Harn 42 ; Manzano Lane 42 ; Segal, Jonathan 42 ; Al-Bakir, Ibrahim 42 ; Khakoo Imran 42 ; Thoua Nora 43 ; Davidson, Katherine 43 ; Miah Jagrul 43 ; Canclini Lisa 43 ; Hall, Alex 43 ; Hayes, Melony 44 ; Myers, Sally 44 ; Talbot, Alison 44 ; Turnbull, Jack 44 ; Whitehead, Emma 44 ; Stamp, Katie 44 ; Pattinson, Alison 44 ; Verghese, Mathew 44 ; Sherris Leanne 44 ; Harvey, Angela 44 ; Hicks, Lucy 45 ; Byrne Tara-Marie 45 ; Cabreros Leilani 45 ; Downing-Wood, Hannah 45 ; Hunter, Sophie 45 ; Prabhudev Hemanth 45 ; Sharmili, Balarajah 45 ; Hajir, Ibraheim 46 ; Torkizadeh Melissa 46 ; Lo, Jonathan W 46 ; Liu, Zhigang 46 ; Sutherland, Helen 47 ; Wilhelmsen Elva 47 ; Mackintosh, Katherine 47 ; Verma, Ajay M 48 ; Juliemol, Sebastian 48 ; Peerally Mohammad Farhad 48 ; Guerdette Anne-marie 48 ; Kent, Alexandra 49 ; Choong Lee Meng 49 ; Pantaloni Benedetta 49 ; Ravdas Pantelis 49 ; Babu, Vadamalayan 50 ; Foley, Stephen 51 ; Arnold, Becky 51 ; Heeley, Cheryl 51 ; Lovegrove, Wayne 51 ; Sowton Donna 51 ; Allsop, Lynne 51 ; Gregory, Heidi 51 ; Smith, Philip J 52 ; Bretland Giovanna 52 ; King, Sarah 52 ; Lofthouse Martina 52 ; Rigby, Lindsey 52 ; Subramanian Sreedhar 52 ; Tyrer, David 52 ; Martin, Kate 52 ; Probert, Christopher 52 ; Kamperidis Nikolaos 53 ; Temi, Adedoyin 53 ; Baden Manisha 53 ; Brown, Jeannette 53 ; Chacko Feba 53 ; Cicchetti Michela 53 ; Saifuddin Mohammad Aamir 2 ; Yesupatham Priya 53 ; Gowda Rohit 54 ; Williams, Maureen 54 ; Kemp, Karen 55 ; Akhand Rima 55 ; Gray Glaxy 55 ; Anu, John 55 ; Maya, John 55 ; Mohammed Tasnim 55 ; Diamond, Sathe 55 ; Jones, Natasha 55 ; Soren, Jennifer 55 ; Sprakes, Michael 56 ; Burton, Julie 56 ; Kane, Patricia 56 ; Lupton, Stephanie 56 ; Bartholomew, Jacqueline 56 ; MacFaul, George 57 ; Scaletta, Diane 57 ; Loria, Siamia 57 ; Williams, Felicity 57 ; Green, Chloe 57 ; Ver Zeljka 57 ; Doona, Mary 58 ; Hogg Ashleigh 58 ; Jeffrey, Lesley 58 ; King, Andrew 58 ; Alexander, Speight R 58 ; Doyle, Jennifer 58 ; Owen, Ruth 58 ; Mowat, Craig 59 ; Rice, Debbie 59 ; MacFarlane, Susan 59 ; MacLeod, Anne 59 ; Samera, Mohammed 59 ; Murray, Shona 59 ; Elliott, Anne 59 ; Morris, Mary Anne 60 ; Coke, Louise 60 ; Hindle, Grace 60 ; Kolokouri Eirini 60 ; Wright, Catherine 60 ; Lee, Claire 60 ; Ward, Nicola 60 ; Dann, Adele 60 ; Lockett, Melanie 61 ; Cranfield, Charlotte 61 ; Jennings, Louise 61 ; Srivastava Ankur 61 ; Ward, Lana 61 ; Jeynes Nouf 61 ; Ranga Poonam 61 ; Rajasekhar Praveen 62 ; Gallagher, Lisa 62 ; Patterson, Linda 62 ; Ward, Jill 62 ; Basnett Rae 62 ; Murphy, Judy 62 ; Parking Lauren 62 ; Lawson, Emma 62 ; Short, Stacey 62 ; Devadason, David 63 ; Moran, Gordon 63 ; Khan, Neelam 63 ; Tarr, Lauren 63 ; Olivia Charmaine 63 ; Limdi Jimmy 64 ; Goulden, Kay 64 ; Javed Asad 64 ; McKenzie, Lauren 64 ; Bhandari Pradeep 65 ; Baker-Moffatt, Michelle 65 ; Dash, Joanne 65 ; Le Poidevin Alison 65 ; Downe Hayley 65 ; Bombeo Lucille 65 ; Blackman, Helen 65 ; Wiles, Alan 66 ; Bloxham Hannah 66 ; Dias, Jose 66 ; Nadar, Evelyn 66 ; Curgenven Hollie 66 ; Macdonald, Jonathan 67 ; Finan Shona 67 ; McMeeken Faye 67 ; Mahmood Misbah 67 ; Shields, Stephanie 67 ; Seenan John Paul 67 ; DeSilva Des 68 ; Malkakorpi Susanna 68 ; Carson, Rachel 68 ; Whiteoak Simon 69 ; Edger-Earley Kelli 69 ; Vamplew Luke 69 ; Ingram, Sarah 70 ; Botfield Sharon 70 ; Hammonds, Fiona 70 ; Clare, James 70 ; Aspinall Gemma 71 ; Hawkins, Sarah 71 ; Marriott Suzie 71 ; Redstone Clare 71 ; Windak Halina 71 ; Ana-Marie, Adam 71 ; Mabb Hannah 71 ; Murray, Charles 12 ; Diaba Cynthia 72 ; Fexy, Joseph 72 ; Pakou Glykeria 72 ; Gleeson, Yvonne 72 ; Berrill, James 73 ; Stroud, Natalie 73 ; Pothecary Carla 73 ; Roche, Lisa 73 ; Turner, Keri 73 ; Deering, Lisa 73 ; Israel, Lynda 73 ; Baker, Evelyn 74 ; Cutler, Sean 74 ; Evans, Rina Mardania 74 ; Nash, Maxine 74 ; Mallison Georgina 74 ; Roynon Anna 74 ; Gordon, John 75 ; Levell Emma 75 ; Zagalo Silvia 75 ; Hoad Ina 75 ; Russell, Richard 76 ; Henderson, Paul 76 ; Millar, Margaret 76 ; Fagbemi, Andrew 77 ; Jennings, Felicia 77 ; Mayor Imelda 77 ; Wilson, Jill 77 ; Alexakis, Christopher 78 ; Michalak, Natalia 78 ; Saunders, John 79 ; Burton, Helen 79 ; Cambridge, Vanessa 79 ; Clark, Tonia 79 ; Ekblad, Charlotte 79 ; Hierons, Sarah 79 ; Katebe Joyce 79 ; Saunsbury Emma 79 ; Perry, Rachel 79 ; Brookes, Matthew 80 ; Davies, Kathryn 80 ; Green, Marie 80 ; Plumbe Ann 80 ; Ormerod, Clare 81 ; Christensen, Helen 81 ; Keen, Anne 81 ; Ogor, Jonathan 81 ; Anthony Alpha 82 ; Newitt, Emily 82 ; Trim, Fiona 82 ; Casey, Ruth 82 ; Seymour, Katherine 82 ; Fogden Edward 83 ; Kalisha, Russell 83 ; Phillips, Anne 84 ; Muaad, Abdulla 84 ; Butterworth, Jeff 85 ; Adams, Colene 85 ; Buckingham, Elizabeth 85 ; Childs, Danielle 85 ; Magness, Alison 85 ; Stickley, Jo 85 ; Motherwell Nichola 85 ; Tonks, Louise 85 ; Gibson, Hannah 85 ; Pajak, S 85 ; Caradog, Thomas 86 ; Brinkworth, Elaine 86 ; Connor, Lynda 86 ; Cook, Amanda 86 ; Rees, Tabitha 86 ; Harford, Rachel 86 ; Wesley, Emma 87 ; Moss, Alison 87 ; Lucas, Jacob 87 ; Lorimer, Claire 87 ; Oleary, Maria 87 ; Dixon, Maxine 87 ; Ramadas Arvind 88 ; Tregonning, Julie 88 ; Okeke Olaku 88 ; Jackson, Wendy 88 ; Koumoutsos Ioannis 89 ; Viji, George 89 ; Kunhunny Swapna 89 ; Laverick Sophie 89 ; Anderson, Isla 89 ; Smith, Sophie 89 ; Patel, Kamal 90 ; Ali, Mariam 90 ; Mhandu Hilda 90 ; Rana Aleem 90 ; Spears, Katherine 90 ; Teixeira Joana 90 ; Pollok, Richard 90 ; Mencias, Mark 90 ; Seaward Abigail 90 ; Sousa, Jessica 90 ; Nooria, Said 90 ; Soomaroo, Mark 90 ; Raspa Valentina 90 ; Tacouri Asha 90 ; Reps, Nicholas 91 ; Martin, Rebecca 91 ; Selinger, Christian 92 ; Carbonell Jenelyn 92 ; Onovira Felicia 92 ; Quartey Doris 92 ; L’Anson Alice 92 ; Ashworth, Andrew 92 ; Bailey, Jessica 92 ; Dunn, Angie 92 ; Mahmood Zahid 93 ; Campbell, Racheal 93 ; Marsh, Liane 93 ; Rahman Monira 94 ; Davies, Sarah 94 ; Habibi, Ruth 94 ; Jessup-Dunton, Ellen 94 ; Teishel, Joefield 94 ; Layug Reina 94 ; Patel, Vinod 95 ; Vere, Joanne 95 ; Turner, Victoria 95 ; Kilroy, Susan 95 ; Walker, Gareth 96 ; Atkins, Stacey 96 ; Growdon Jasmine 96 ; McNeill, Charlotte 96 ; Cooney, Rachel 97 ; Bennett, Lillie 97 ; Bowlas Louise 97 ; Shariff Sharafaath 97 ; Fraser, Aileen 98 ; Punnette Dwayne 98 ; Bishop-Hurman, Charlotte 98 ; Undrell, Elizabeth 98 ; Belfield, Katherine 98 ; Din Said 99 ; Addleton Catherine 99 ; Appleby, Marie 99 ; Brown, Johanna 99 ; Holding, Kathleen 99 ; Hooper, Patricia 100 ; deCaestecker, John 100 ; Watchorn Olivia 100 ; Hayward, Chris 101 ; Inniss, Susan 101 ; Pritchard, Lucy 101 ; Rudge, Karen 101 ; Carney, Amanda 101 ; Andreyev Jervoise 102 ; Hayhurst, Caroline 102 ; Lockwood, Carol 102 ; Osborne, Lynn 102 ; Roper, Amanda 102 ; Warner, Karen 102 ; Hindle, Julia 102 ; Watt, Caroline 102 ; Szymiczek Kinga 102 ; Mehta Shameer 103 ; Bell, James 103 ; Blad, William 103 ; Whitley, Lisa 103 ; Durai, Dhamaraj 104 ; Baker, Mark 104 ; Sivamurugan, Elizabeth John 104 ; Evans, Mim 104 ; Cummings, Fraser 105 ; Harris, Clare 105 ; Jones, Amy 105 ; Krauze Liga 105 ; Rahmany Sohail 105 ; Earl, Michelle 105 ; Vowles, Jenny 105 ; Torokwa Audrey 105 ; Petrova Mirela 105 ; Procter, Andrew 105 ; Stanley, Jo 105 ; Silvamoniz Claudia 105 ; Bettey Marion 105 ; Wahid Amar 106 ; Morrison, Zoe 106 ; Thomas-Turner, Rhian 106 ; Yendle Louise 106 ; Muller, Jennifer 106 ; Mitchell, Marcus 107 ; Kirkwood, John 107 ; Barnes, Anna 107 ; Chaudhary Rakesh 108 ; Claridge, Melanie 108 ; Ellis, Chiara 108 ; Kemp, Cheryl 108 ; Ogwa, Tobi 108 ; Jentus, Milton 108 ; Johnston, Emma 109 ; Oblak Metod 109 ; Godden, Jo 110 ; Lees, Charlie 111 ; Alexander, Debbie 111 ; Covil Kate 111 ; Derikx Lauranne 111 ; Sryros, Siakavellas 111 ; Baxter, Helen 111 ; Robertson, Scott 111 ; Smith, Linda 111 ; Poulose Beena 111 ; Colemam Anne 111 ; Balint Margareta 111 ; Rhys-Jones, Gareth 111 ; Johns, Kerrie 112 ; Hughes, Rachel 112 ; Phipps, Janet 112 ; Taylor, Abigail 112 ; MacPhee, Catherine 112 ; Brooks, Suzanne 112 ; Smith, Katie 113 ; Howard, Linda 113 ; Wood, Dianne 113 ; Muddu Ajay 114 ; Barman, Laura 114 ; Mallinson, Janine 114 ; Neale, Tania 114 ; Ionita, Diana 114 ; Elliot, Kerry 114 ; Turnball Alison 114 ; Iola, Thomas 115 ; Andrews, Kelly 115 ; Sutton, Jonathon 115 ; Jones, Caroline Mulvaney 115 ; Roberts, Julia 115 ; Bishop, Jeannie 115 

1  Royal Devon and Exeter NHS Foundation Trust, Department of Gastroenterology, Exeter, UK (GRID:grid.419309.6) (ISNI:0000 0004 0495 6261); University of Exeter, Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, Exeter, UK (GRID:grid.8391.3) (ISNI:0000 0004 1936 8024) 
2  St Marks Hospital and Academic Institute, Department of Gastroenterology, London, UK (GRID:grid.416510.7); Imperial College London, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
3  Imperial College London, Department of Infectious Disease, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
4  Imperial College London, Department of Immunology and Inflammation, London, United Kingdom (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
5  Imperial College London, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
6  University of Exeter, Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, Exeter, UK (GRID:grid.8391.3) (ISNI:0000 0004 1936 8024); Royal Devon and Exeter NHS Foundation Trust, Department of Biochemistry, Exeter Clinical Laboratory International, Exeter, UK (GRID:grid.419309.6) (ISNI:0000 0004 0495 6261) 
7  University of Exeter, Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, Exeter, UK (GRID:grid.8391.3) (ISNI:0000 0004 1936 8024) 
8  Royal Devon and Exeter NHS Foundation Trust, Department of Biochemistry, Exeter Clinical Laboratory International, Exeter, UK (GRID:grid.419309.6) (ISNI:0000 0004 0495 6261) 
9  Hull University Teaching Hospitals NHS Trust, IBD Unit, Department of Gastroenterology, Hull, UK (GRID:grid.9481.4) (ISNI:0000 0004 0412 8669); University of Hull, Hull York Medical School, Hull, UK (GRID:grid.9481.4) (ISNI:0000 0004 0412 8669) 
10  Imperial College London, Department of Metabolism, Digestion and Reproduction, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College Healthcare NHS Trust, Department of Gastroenterology, London, UK (GRID:grid.417895.6) (ISNI:0000 0001 0693 2181) 
11  Royal Free London NHS Foundation Trust, Department of Gastroenterology, London, UK (GRID:grid.437485.9) (ISNI:0000 0001 0439 3380); The Francis Crick Institute, Genetic Mechanisms of Disease Laboratory, London, UK (GRID:grid.451388.3) (ISNI:0000 0004 1795 1830); University of Cambridge, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
12  Royal Free London NHS Foundation Trust, Department of Gastroenterology, London, UK (GRID:grid.437485.9) (ISNI:0000 0001 0439 3380) 
13  St Marks Hospital and Academic Institute, Department of Gastroenterology, London, UK (GRID:grid.416510.7) 
14  Guy’s and St Thomas’ NHS Foundation Trust, Department of Gastroenterology, London, UK (GRID:grid.420545.2) (ISNI:0000 0004 0489 3985); King’s College London, School of Immunology & Microbial Sciences, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
15  Western General Hospital, NHS Lothian, Department of Gastroenterology, Edinburgh, UK (GRID:grid.417068.c) (ISNI:0000 0004 0624 9907); The Queen’s Medical Research Institute, The University of Edinburgh, Centre for Inflammation Research, Edinburgh, UK (GRID:grid.511172.1) (ISNI:0000 0004 0613 128X) 
16  Royal London Hospital, Barts Health NHS Trust, Department of Gastroenterology, London, UK (GRID:grid.416041.6) (ISNI:0000 0001 0738 5466); Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, Centre for Immunobiology, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133) 
17  Newcastle upon Tyne Hospitals NHS Foundation Trust, Department of Gastroenterology, Newcastle upon Tyne, UK (GRID:grid.420004.2) (ISNI:0000 0004 0444 2244); Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK (GRID:grid.1006.7) (ISNI:0000 0001 0462 7212) 
18  Western General Hospital, NHS Lothian, Department of Gastroenterology, Edinburgh, UK (GRID:grid.417068.c) (ISNI:0000 0004 0624 9907); Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
19  Imperial College London, Department of Infectious Disease, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Royal Brompton Hospital and Harefield Hospitals, Lung Division, London, UK (GRID:grid.439338.6) (ISNI:0000 0001 1114 4366) 
20  Barts Health NHS Trust, London, UK (GRID:grid.139534.9) (ISNI:0000 0001 0372 5777); Barts Health NHS Trust (Paediatric), London, UK (GRID:grid.139534.9) (ISNI:0000 0001 0372 5777) 
21  Barts Health NHS Trust, London, UK (GRID:grid.139534.9) (ISNI:0000 0001 0372 5777); Darlington Memorial Hospital, County Durham, UK (GRID:grid.413477.2) (ISNI:0000 0004 0400 3698) 
22  Barts Health NHS Trust, London, UK (GRID:grid.139534.9) (ISNI:0000 0001 0372 5777) 
23  Basingstoke and North Hampshire Hospital, Basingstoke, UK (GRID:grid.414262.7) (ISNI:0000 0004 0400 7883) 
24  Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UK (GRID:grid.498025.2) (ISNI:0000 0004 0376 6175) 
25  Bolton NHS Foundation Trust, Bolton, UK (GRID:grid.487142.c) (ISNI:0000 0004 0377 7907) 
26  Borders General Hospital, Scotland, UK (GRID:grid.414563.1) (ISNI:0000 0004 0624 3644) 
27  Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, UK (GRID:grid.487190.3) (ISNI:0000 0004 0412 6700) 
28  Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386) 
29  University of Cambridge, Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
30  Chelsea and Westminster Hospital NHS Foundation Trust, London, UK (GRID:grid.428062.a) (ISNI:0000 0004 0497 2835) 
31  Chesterfield Royal Hospital, Chesterfield, UK (GRID:grid.413868.0) (ISNI:0000 0004 0417 2571) 
32  Countess of Chester Hospital NHS Foundation Trust, Chester, UK (GRID:grid.412921.d) (ISNI:0000 0004 0387 7190) 
33  Darlington Memorial Hospital, County Durham, UK (GRID:grid.413477.2) (ISNI:0000 0004 0400 3698) 
34  Dartford and Gravesham NHS Trust, Kent, UK (GRID:grid.439553.d) (ISNI:0000 0004 0394 2634) 
35  The Dudley Group NHS Foundation Trust, West Midlands, UK (GRID:grid.464540.7) (ISNI:0000 0004 0469 4759) 
36  East and North Hertfordshire NHS Trust, Stevenage, UK (GRID:grid.439624.e) (ISNI:0000 0004 0467 7828) 
37  East Lancashire Hospitals NHS Trust, Blackburn, UK (GRID:grid.439642.e) (ISNI:0000 0004 0489 3782) 
38  Glangwili Hospital, Carmarthen, UK (GRID:grid.439642.e) 
39  Great Ormond Street Hospital, London, UK (GRID:grid.420468.c) 
40  Great Western Hospitals NHS Foundation Trust, Swindon, UK (GRID:grid.440177.1) (ISNI:0000 0004 0470 0565) 
41  Guy’s and St Thomas’ NHS Foundation Trust, London, UK (GRID:grid.420545.2) (ISNI:0000 0004 0489 3985) 
42  The Hillingdon Hospitals NHS Foundation Trust, Uxbridge, UK (GRID:grid.440199.1) (ISNI:0000 0004 0476 7073) 
43  Homerton University Hospital Foundation Trust, London, UK (GRID:grid.439591.3) (ISNI:0000 0004 0399 2770) 
44  Hull University Teaching Hospitals NHS Trust, Hull, UK (GRID:grid.9481.4) (ISNI:0000 0004 0412 8669) 
45  Imperial College Healthcare NHS Trust, London, UK (GRID:grid.417895.6) (ISNI:0000 0001 0693 2181) 
46  Imperial College London, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
47  James Paget University Hospitals NHS Foundation Trust, Great Yarmouth, UK (GRID:grid.507530.4) (ISNI:0000 0004 0406 4327) 
48  Kettering General Hospital, Kettering, UK (GRID:grid.415192.a) (ISNI:0000 0004 0400 5589) 
49  King’s College Hospital NHS Foundation Trust, London, UK (GRID:grid.429705.d) (ISNI:0000 0004 0489 4320) 
50  King’s College Hospital NHS Foundation Trust (Paediatric), London, UK (GRID:grid.429705.d) (ISNI:0000 0004 0489 4320) 
51  King’s Mill Hospital, Nottinghamshire, UK (GRID:grid.415352.4) (ISNI:0000 0004 1756 4726) 
52  Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK (GRID:grid.10025.36) (ISNI:0000 0004 1936 8470) 
53  London North West University Healthcare NHS Trust, London, UK (GRID:grid.439803.5) 
54  Maidstone and Tunbridge Wells NHS Trust, Tunbridge Wells, UK (GRID:grid.439813.4) (ISNI:0000 0000 8822 7920) 
55  Manchester University NHS Foundation Trust, Manchester, UK (GRID:grid.498924.a) (ISNI:0000 0004 0430 9101) 
56  The Mid Yorkshire Hospitals NHS Trust, Wakefield, UK (GRID:grid.439224.a) (ISNI:0000 0001 0372 5769) 
57  Milton Keynes University Hospital, Milton Keynes, UK (GRID:grid.415667.7) 
58  Newcastle Hospitals NHS Foundation Trust, Newcastle, UK (GRID:grid.420004.2) (ISNI:0000 0004 0444 2244) 
59  Ninewells Hospital & Medical School, Dundee, UK (GRID:grid.416266.1) (ISNI:0000 0000 9009 9462) 
60  Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK (GRID:grid.240367.4) (ISNI:0000 0004 0445 7876) 
61  North Bristol NHS Trust, Bristol, UK (GRID:grid.418484.5) (ISNI:0000 0004 0380 7221) 
62  North Tyneside General Hospital, North Shields, UK (GRID:grid.416512.5) (ISNI:0000 0004 0402 1394) 
63  Nottingham University Hospitals NHS Trust, Nottingham, UK (GRID:grid.240404.6) (ISNI:0000 0001 0440 1889) 
64  The Pennine Acute Hospitals NHS Trust, Manchester, UK (GRID:grid.437504.1) (ISNI:0000 0000 9032 4308) 
65  Portsmouth Hospitals NHS Trust, Portsmouth, UK (GRID:grid.418709.3) (ISNI:0000 0004 0456 1761) 
66  The Queen Elizabeth Hospital Kings Lynn NHS Trust, Kings Lynn, UK (GRID:grid.470208.9) (ISNI:0000 0004 0415 9545) 
67  Queen Elizabeth University Hospital, Glasgow, UK (GRID:grid.511123.5) (ISNI:0000 0004 5988 7216) 
68  Royal Berkshire NHS Foundation Trust, Reading, UK (GRID:grid.419297.0) (ISNI:0000 0000 8487 8355) 
69  University Hospitals Dorset NHS Foundation Trust, Dorset, UK (GRID:grid.451052.7) (ISNI:0000 0004 0581 2008) 
70  Royal Cornwall Hospitals NHS Trust, Cornwall, UK (GRID:grid.412944.e) (ISNI:0000 0004 0474 4488) 
71  Royal Devon and Exeter NHS Foundation Trust, Exeter, UK (GRID:grid.419309.6) (ISNI:0000 0004 0495 6261) 
72  Royal Free London NHS Foundation Trust, London, UK (GRID:grid.437485.9) (ISNI:0000 0001 0439 3380) 
73  Royal Glamorgan Hospital, Pontyclun, UK (GRID:grid.414348.e) (ISNI:0000 0004 0649 0178) 
74  Royal Gwent Hospital, Newport, UK (GRID:grid.461312.3) (ISNI:0000 0000 9616 5600) 
75  Royal Hampshire County Hospital, Winchester, UK (GRID:grid.416128.8) (ISNI:0000 0000 9300 7922) 
76  Royal Hospital for Sick Children, Edinburgh, UK (GRID:grid.496757.e) (ISNI:0000 0004 0624 7987) 
77  Royal Manchester Children’s Hospital, Manchester, UK (GRID:grid.415910.8) (ISNI:0000 0001 0235 2382) 
78  Royal Surrey County Hospital, Surrey, UK (GRID:grid.416224.7) (ISNI:0000 0004 0417 0648) 
79  Royal United Hospitals Bath, Bath, UK (GRID:grid.413029.d) (ISNI:0000 0004 0374 2907) 
80  The Royal Wolverhampton NHS Trust, Wolverhampton, UK (GRID:grid.439674.b) (ISNI:0000 0000 9830 7596) 
81  Salford Royal NHS Foundation Trust, Salford, UK (GRID:grid.412346.6) (ISNI:0000 0001 0237 2025) 
82  Salisbury District Hospital, Salisbury, UK (GRID:grid.416642.3) (ISNI:0000 0004 0417 0779) 
83  Sandwell and West Birmingham NHS Trust, Birmingham, UK (GRID:grid.416642.3) 
84  Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK (GRID:grid.31410.37) (ISNI:0000 0000 9422 8284) 
85  Shrewsbury and Telford Hospital NHS Trust, Shrewsbury, UK (GRID:grid.439417.c) (ISNI:0000 0004 0472 4225) 
86  Singleton Hospital, Swansea, UK (GRID:grid.415947.a) (ISNI:0000 0004 0649 0274) 
87  Somerset NHS Foundation Trust, Taunton, UK (GRID:grid.500936.9) (ISNI:0000 0000 8621 4130) 
88  South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK (GRID:grid.440194.c) (ISNI:0000 0004 4647 6776) 
89  Southend University Hospital NHS Foundation Trust, Essex, UK (GRID:grid.440512.6) (ISNI:0000 0004 0484 266X) 
90  St George’s University Hospitals NHS Foundation Trust, London, UK (GRID:grid.451349.e) 
91  St George’s University Hospitals NHS Foundation Trust (Paediatric), London, UK (GRID:grid.451349.e) 
92  St James’s University Hospital, Leeds, UK (GRID:grid.443984.6) (ISNI:0000 0000 8813 7132) 
93  Stockport NHS Foundation Trust, Stockport, UK (GRID:grid.439622.8) (ISNI:0000 0004 0469 2913) 
94  Surrey and Sussex Healthcare NHS Trust, Surrey, UK (GRID:grid.439641.d) (ISNI:0000 0004 0458 0698) 
95  Tameside and Glossop Integrated Care NHS Foundation Trust, Greater Manchester, UK (GRID:grid.507528.d) (ISNI:0000 0004 0494 3807) 
96  Torbay and South Devon NHS Foundation Trust, Torquay, UK (GRID:grid.439442.c) (ISNI:0000 0004 0474 1025) 
97  University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK (GRID:grid.412563.7) (ISNI:0000 0004 0376 6589) 
98  University Hospitals Bristol NHS Foundation Trust, Bristol, UK (GRID:grid.410421.2) (ISNI:0000 0004 0380 7336) 
99  University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK (GRID:grid.508499.9) 
100  University Hospitals of Leicester NHS Trust, Leicester, UK (GRID:grid.269014.8) (ISNI:0000 0001 0435 9078) 
101  University Hospitals Plymouth NHS Trust, Plymouth, UK (GRID:grid.418670.c) (ISNI:0000 0001 0575 1952) 
102  United Lincolnshire Hospitals NHS Trust, Lincoln, UK (GRID:grid.433807.b) (ISNI:0000 0001 0642 1066) 
103  University College London Hospitals NHS Foundation Trust, London, UK (GRID:grid.52996.31) (ISNI:0000 0000 8937 2257) 
104  University Hospital Llandough, Penarth, UK (GRID:grid.416025.4) (ISNI:0000 0004 0648 9396) 
105  University Hospital Southampton NHS Foundation Trust, Southampton, UK (GRID:grid.430506.4) (ISNI:0000 0004 0465 4079) 
106  University Hospital of Wales (Paediatrics), Cardiff, UK (GRID:grid.241103.5) (ISNI:0000 0001 0169 7725) 
107  University of Exeter, Exeter NIHR Clinical Research Facility, Exeter, UK (GRID:grid.8391.3) (ISNI:0000 0004 1936 8024) 
108  West Hertfordshire Hospitals NHS Trust, Hertfordshire, UK (GRID:grid.439697.6) (ISNI:0000 0004 0483 1442) 
109  West Middlesex University Hospital, London, UK (GRID:grid.461588.6) (ISNI:0000 0004 0399 2500) 
110  West Suffolk NHS Foundation Trust, Ipswich, UK (GRID:grid.440202.0) (ISNI:0000 0001 0575 1944) 
111  Western General Hospital, Edinburgh, UK (GRID:grid.417068.c) (ISNI:0000 0004 0624 9907) 
112  Withybush General Hospital, Haverfordwest, UK (GRID:grid.417148.f) (ISNI:0000 0004 0649 0039) 
113  Yeovil District Hospital NHS Foundation Trust, Yeovil, UK (GRID:grid.440204.6) (ISNI:0000 0004 0487 0310) 
114  York Teaching Hospital NHS Foundation Trust, York, UK (GRID:grid.439905.2) (ISNI:0000 0000 9626 5193) 
115  Ysbyty Gwynedd, Bangor, UK (GRID:grid.437505.0) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-28517-z
ProQuest document ID
2640564771
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.