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1. Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Author

Jannik Boos, Caspar I. van der Made, Gayatri Ramakrishnan, Eamon Coughlan, Rosanna Asselta, Britt-Sabina Löscher, Luca V.C. Valenti, Rafael de Cid, Luis Bujanda, Antonio Julià, Erola Pairo-Castineira, J. Kenneth Baillie, Sandra May, Berina Zametica, Julia Heggemann, Agustín Albillos, Jesus M. Banales, Jordi Barretina, Natalia Blay, Paolo Bonfanti, Maria Buti, Javier Fernandez, Sara Marsal, Daniele Prati, Luisa Ronzoni, Nicoletta Sacchi, Joachim L. Schultze, Olaf Riess, Andre Franke, Konrad Rawlik, David Ellinghaus, Alexander Hoischen, Axel Schmidt, Kerstin U. Ludwig, Valeria Rimoldi, Elvezia M. Paraboschi, Alessandra Bandera, Flora Peyvandi, Giacomo Grasselli, Francesco Blasi, Francesco Malvestiti, Serena Pelusi, Cristiana Bianco, Lorenzo Miano, Angela Lombardi, Pietro Invernizzi, Alessio Gerussi, Giuseppe Citerio, Andrea Biondi, Maria Grazia Valsecchi, Marina Elena Cazzaniga, Giuseppe Foti, Ilaria Beretta, Mariella D'Angiò, Laura Rachele Bettini, Xavier Farré, Susana Iraola-Guzmán, Manolis Kogevinas, Gemma Castaño-Vinyals, Koldo Garcia-Etxebarria, Beatriz Nafria, Mauro D'Amato, Adriana Palom, Colin Begg, Sara Clohisey, Charles Hinds, Peter Horby, Julian Knight, Lowell Ling, David Maslove, Danny McAuley, Johnny Millar, Hugh Montgomery, Alistair Nichol, Peter J.M. Openshaw, Alexandre C. Pereira, Chris P. Ponting, Kathy Rowan, Malcolm G. Semple, Manu Shankar-Hari, Charlotte Summers, Timothy Walsh, Latha Aravindan, Ruth Armstrong, Heather Biggs, Ceilia Boz, Adam Brown, Richard Clark, Audrey Coutts, Judy Coyle, Louise Cullum, Sukamal Das, Nicky Day, Lorna Donnelly, Esther Duncan, Angie Fawkes, Paul Fineran, Max Head Fourman, Anita Furlong, James Furniss, Bernadette Gallagher, Tammy Gilchrist, Ailsa Golightly, Fiona Griffiths, Katarzyna Hafezi, Debbie Hamilton, Ross Hendry, Andy Law, Dawn Law, Rachel Law, Sarah Law, Rebecca Lidstone-Scott, Louise Macgillivray, Alan Maclean, Hanning Mal, Sarah McCafferty, Ellie Mcmaster, Jen Meikle, Shona C. Moore, Kirstie Morrice, Lee Murphy, Sheena Murphy, Mybaya Hellen, Wilna Oosthuyzen, Chenqing Zheng, Jiantao Chen, Nick Parkinson, Trevor Paterson, Katherine Schon, Andrew Stenhouse, Mihaela Das, Maaike Swets, Helen Szoor-McElhinney, Filip Taneski, Lance Turtle, Tony Wackett, Mairi Ward, Jane Weaver, Nicola Wrobel, Marie Zechner, Gill Arbane, Aneta Bociek, Sara Campos, Neus Grau, Tim Owen Jones, Rosario Lim, Martina Marotti, Marlies Ostermann, Christopher Whitton, Zoe Alldis, Raine Astin-Chamberlain, Fatima Bibi, Jack Biddle, Sarah Blow, Matthew Bolton, Catherine Borra, Ruth Bowles, Maudrian Burton, Yasmin Choudhury, David Collier, Amber Cox, Amy Easthope, Patrizia Ebano, Stavros Fotiadis, Jana Gurasashvili, Rosslyn Halls, Pippa Hartridge, Delordson Kallon, Jamila Kassam, Ivone Lancoma-Malcolm, Maninderpal Matharu, Peter May, Oliver Mitchelmore, Tabitha Newman, Mital Patel, Jane Pheby, Irene Pinzuti, Zoe Prime, Oleksandra Prysyazhna, Julian Shiel, Melanie Taylor, Carey Tierney, Suzanne Wood, Anne Zak, Olivier Zongo, Stephen Bonner, Keith Hugill, Jessica Jones, Steven Liggett, Evie Headlam, Nageswar Bandla, Minnie Gellamucho, Michelle Davies, Christopher Thompson, Marwa Abdelrazik, Dhanalakshmi Bakthavatsalam, Munzir Elhassan, Arunkumar Ganesan, Anne Haldeos, Jeronimo Moreno-Cuesta, Dharam Purohit, Rachel Vincent, Kugan Xavier, Kumar Rohit, Frater Alasdair, Malik Saleem, Carter David, Jenkins Samuel, Zoe Lamond, Wall Alanna, Jaime Fernandez-Roman, David O. Hamilton, Emily Johnson, Brian Johnston, Maria Lopez Martinez, Suleman Mulla, David Shaw, Alicia A.C. Waite, Victoria Waugh, Ingeborg D. Welters, Karen Williams, Anna Cavazza, Maeve Cockrell, Eleanor Corcoran, Maria Depante, Clare Finney, Ellen Jerome, Mark McPhail, Monalisa Nayak, Harriet Noble, Kevin O'Reilly, Evita Pappa, Rohit Saha, Sian Saha, John Smith, Abigail Knighton, David Antcliffe, Dorota Banach, Stephen Brett, Phoebe Coghlan, Ziortza Fernandez, Anthony Gordon, Roceld Rojo, Sonia Sousa Arias, Maie Templeton, Megan Meredith, Lucy Morris, Lucy Ryan, Amy Clark, Julia Sampson, Cecilia Peters, Martin Dent, Margaret Langley, Saima Ashraf, Shuying Wei, Angela Andrew, Archana Bashyal, Neil Davidson, Paula Hutton, Stuart McKechnie, Jean Wilson, David Baptista, Rebecca Crowe, Rita Fernandes, Rosaleen Herdman-Grant, Anna Joseph, Denise O'Connor, Meryem Allen, Adam Loveridge, India McKenley, Eriko Morino, Andres Naranjo, Richard Simms, Kathryn Sollesta, Andrew Swain, Harish Venkatesh, Jacyntha Khera, Jonathan Fox, Gillian Andrew, Lucy Barclay, Marie Callaghan, Rachael Campbell, Sarah Clark, Dave Hope, Lucy Marshall, Corrienne McCulloch, Kate Briton, Jo Singleton, Sohphie Birch, Lutece Brimfield, Zoe Daly, David Pogson, Steve Rose, Ceri Battle, Elaine Brinkworth, Rachel Harford, Carl Murphy, Luke Newey, Tabitha Rees, Marie Williams, Sophie Arnold, Petra Polgarova, Katerina Stroud, Eoghan Meaney, Megan Jones, Anthony Ng, Shruti Agrawal, Nazima Pathan, Deborah White, Esther Daubney, Kay Elston, Lina Grauslyte, Musarat Hussain, Mandeep Phull, Tatiana Pogreban, Lace Rosaroso, Erika Salciute, George Franke, Joanna Wong, Aparna George, Laura Ortiz-Ruiz de Gordoa, Emily Peasgood, Claire Phillips, Michelle Bates, Jo Dasgin, Jaspret Gill, Annette Nilsson, James Scriven, Carlos Castro Delgado, Deborah Dawson, Lijun Ding, Georgia Durrant, Obiageri Ezeobu, Sarah Farnell-Ward, Abiola Harrison, Rebecca Kanu, Susannah Leaver, Elena Maccacari, Soumendu Manna, Romina Pepermans Saluzzio, Joana Queiroz, Tinashe Samakomva, Christine Sicat, Joana Texeira, Edna Fernandes Da Gloria, Ana Lisboa, John Rawlins, Jisha Mathew, Ashley Kinch, William James Hurt, Nirav Shah, Victoria Clark, Maria Thanasi, Nikki Yun, Kamal Patel, Sara Bennett, Emma Goodwin, Matthew Jackson, Alissa Kent, Clare Tibke, Wiesia Woodyatt, Ahmed Zaki, Azmerelda Abraheem, Peter Bamford, Kathryn Cawley, Charlie Dunmore, Maria Faulkner, Rumanah Girach, Helen Jeffrey, Rhianna Jones, Emily London, Imrun Nagra, Farah Nasir, Hannah Sainsbury, Clare Smedley, Tahera Patel, Matthew Smith, Srikanth Chukkambotla, Aayesha Kazi, Janice Hartley, Joseph Dykes, Muhammad Hijazi, Sarah Keith, Meherunnisa Khan, Janet Ryan-Smith, Philippa Springle, Jacqueline Thomas, Nick Truman, Samuel Saad, Dabheoc Coleman, Christopher Fine, Roseanna Matt, Bethan Gay, Jack Dalziel, Syamlan Ali, Drew Goodchild, Rhiannan Harling, Ravi Bhatterjee, Wendy Goddard, Chloe Davison, Stephen Duberly, Jeanette Hargreaves, Rachel Bolton, Miriam Davey, David Golden, Rebecca Seaman, Shiney Cherian, Sean Cutler, Anne Emma Heron, Anna Roynon-Reed, Tamas Szakmany, Gemma Williams, Owen Richards, Yusuf Cheema, Hollie Brooke, Sarah Buckley, Jose Cebrian Suarez, Ruth Charlesworth, Karen Hansson, John Norris, Alice Poole, Alastair Rose, Rajdeep Sandhu, Brendan Sloan, Elizabeth Smithson, Muthu Thirumaran, Veronica Wagstaff, Alexandra Metcalfe, Mark Brunton, Jess Caterson, Holly Coles, Matthew Frise, Sabi Gurung Rai, Nicola Jacques, Liza Keating, Emma Tilney, Shauna Bartley, Parminder Bhuie, Sian Gibson, Amanda Lyle, Fiona McNeela, Jayachandran Radhakrishnan, Alistair Hughes, Bryan Yates, Jessica Reynolds, Helen Campbell, Maria Thompsom, Steve Dodds, Stacey Duffy, Sandra Greer, Karen Shuker, Ascanio Tridente, Reena Khade, Ashok Sundar, George Tsinaslanidis, Isobel Birkinshaw, Joseph Carter, Kate Howard, Joanne Ingham, Rosie Joy, Harriet Pearson, Samantha Roche, Zoe Scott, Hollie Bancroft, Mary Bellamy, Margaret Carmody, Jacqueline Daglish, Faye Moore, Joanne Rhodes, Mirriam Sangombe, Salma Kadiri, Maria Croft, Ian White, Victoria Frost, Maia Aquino, Rajeev Jha, Vinodh Krishnamurthy, Lai Lim, Li Lim, Edward Combes, Teishel Joefield, Sonja Monnery, Valerie Beech, Sallyanne Trotman, Christine Almaden-Boyle, Pauline Austin, Louise Cabrelli, Stephen Cole, Matt Casey, Susan Chapman, Clare Whyte, Yolanda Baird, Aaron Butler, Indra Chadbourn, Linda Folkes, Heather Fox, Amy Gardner, Raquel Gomez, Gillian Hobden, Luke Hodgson, Kirsten King, Michael Margarson, Tim Martindale, Emma Meadows, Dana Raynard, Yvette Thirlwall, David Helm, Jordi Margalef, Kristine Criste, Rebecca Cusack, Kim Golder, Hannah Golding, Oliver Jones, Samantha Leggett, Michelle Male, Martyna Marani, Kirsty Prager, Toran Williams, Belinda Roberts, Karen Salmon, Peter Anderson, Katie Archer, Karen Austin, Caroline Davis, Alison Durie, Olivia Kelsall, Jessica Thrush, Charlie Vigurs, Laura Wild, Hannah-Louise Wood, Helen Tranter, Alison Harrison, Nicholas Cowley, Michael McAlindon, Andrew Burtenshaw, Stephen Digby, Emma Low, Aled Morgan, Naiara Cother, Tobias Rankin, Sarah Clayton, Alex McCurdy, Cecilia Ahmed, Balvinder Baines, Sarah Clamp, Julie Colley, Risna Haq, Anne Hayes, Jonathan Hulme, Samia Hussain, Sibet Joseph, Rita Kumar, Zahira Maqsood, Manjit Purewal, Leonie Benham, Zena Bradshaw, Joanna Brown, Melanie Caswell, Jason Cupitt, Sarah Melling, Stephen Preston, Nicola Slawson, Emma Stoddard, Scott Warden, Bethan Deacon, Ceri Lynch, Carla Pothecary, Lisa Roche, Gwenllian Sera Howe, Jayaprakash Singh, Keri Turner, Hannah Ellis, Natalie Stroud, Jodie Hunt, Joy Dearden, Emma Dobson, Andy Drummond, Michelle Mulcahy, Sheila Munt, Grainne O'Connor, Jennifer Philbin, Chloe Rishton, Redmond Tully, Sarah Winnard, Susanne Cathcart, Katharine Duffy, Alex Puxty, Kathryn Puxty, Lynne Turner, Jane Ireland, Gary Semple, Kate Long, Simon Whiteley, Elizabeth Wilby, Bethan Ogg, Amanda Cowton, Andrea Kay, Melanie Kent, Kathryn Potts, Ami Wilkinson, Suzanne Campbell, Ellen Brown, Julie Melville, Jay Naisbitt, Rosane Joseph, Maria Lazo, Olivia Walton, Alan Neal, Peter Alexander, Schvearn Allen, Joanne Bradley-Potts, Craig Brantwood, Jasmine Egan, Timothy Felton, Grace Padden, Luke Ward, Stuart Moss, Susannah Glasgow, Lynn Abel, Michael Brett, Brian Digby, Lisa Gemmell, James Hornsby, Patrick MacGoey, Pauline O'Neil, Richard Price, Natalie Rodden, Kevin Rooney, Radha Sundaram, Nicola Thomson, Bridget Hopkins, Laura Thrasyvoulou, Heather Willis, Martyn Clark, Martina Coulding, Edward Jude, Jacqueline McCormick, Oliver Mercer, Darsh Potla, Hafiz Rehman, Heather Savill, Victoria Turner, Charlotte Downes, Kathleen Holding, Katie Riches, Mary Hilton, Mel Hayman, Deepak Subramanian, Priya Daniel, Oluronke Adanini, Nikhil Bhatia, Maines Msiska, Rebecca Collins, Ian Clement, Bijal Patel, A. Gulati, Carole Hays, K. Webster, Anne Hudson, Andrea Webster, Elaine Stephenson, Louise McCormack, Victoria Slater, Rachel Nixon, Helen Hanson, Maggie Fearby, Sinead Kelly, Victoria Bridgett, Philip Robinson, Julie Camsooksai, Charlotte Humphrey, Sarah Jenkins, Henrik Reschreiter, Beverley Wadams, Yasmin Death, Victoria Bastion, Daphene Clarke, Beena David, Harriet Kent, Rachel Lorusso, Gamu Lubimbi, Sophie Murdoch, Melchizedek Penacerrada, Alastair Thomas, Jennifer Valentine, Ana Vochin, Retno Wulandari, Brice Djeugam, Gillian Bell, Katy English, Amro Katary, Louise Wilcox, Michelle Bruce, Karen Connolly, Tracy Duncan, Helen T-Michael, Gabriella Lindergard, Samuel Hey, Claire Fox, Jordan Alfonso, Laura Jayne Durrans, Jacinta Guerin, Bethan Blackledge, Jade Harris, Martin Hruska, Ayaa Eltayeb, Thomas Lamb, Tracey Hodgkiss, Lisa Cooper, Joanne Rothwell, Angela Allan, Felicity Anderson, Callum Kaye, Jade Liew, Jasmine Medhora, Teresa Scott, Erin Trumper, Adriana Botello, Liana Lankester, Nikitas Nikitas, Colin Wells, Bethan Stowe, Kayleigh Spencer, Craig Brandwood, Lara Smith, Katie Birchall, Laurel Kolakaluri, Deborah Baines, Anila Sukumaran, Elena Apetri, Cathrine Basikolo, Laura Catlow, Bethan Charles, Paul Dark, Reece Doonan, Alice Harvey, Daniel Horner, Karen Knowles, Stephanie Lee, Diane Lomas, Chloe Lyons, Tracy Marsden, Danielle McLaughlan, Liam McMorrow, Jessica Pendlebury, Jane Perez, Maria Poulaka, Nicola Proudfoot, Melanie Slaughter, Kathryn Slevin, Vicky Thomas, Danielle Walker, Angiy Michael, Matthew Collis, Tracey Cosier, Gemma Millen, Neil Richardson, Natasha Schumacher, Heather Weston, James Rand, Nicola Baxter, Steven Henderson, Sophie Kennedy-Hay, Christopher McParland, Laura Rooney, Malcolm Sim, Gordan McCreath, Louise Akeroyd, Shereen Bano, Matt Bromley, Lucy Gurr, Tom Lawton, James Morgan, Kirsten Sellick, Deborah Warren, Brian Wilkinson, Janet McGowan, Camilla Ledgard, Amelia Stacey, Kate Pye, Ruth Bellwood, Michael Bentley, Jeremy Bewley, Zoe Garland, Lisa Grimmer, Bethany Gumbrill, Rebekah Johnson, Katie Sweet, Denise Webster, Georgia Efford, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Jocelyn Keshet-Price, Georgina Randell, Katie Stammers, Maria Bokhari, Vanessa Linnett, Rachael Lucas, Wendy McCormick, Jenny Ritzema, Amanda Sanderson, Helen Wild, Anthony Rostron, Alistair Roy, Lindsey Woods, Sarah Cornell, Fiona Wakinshaw, Kimberley Rogerson, Jordan Jarmain, Robert Parker, Amie Reddy, Ian Turner-Bone, Laura Wilding, Peter Harding, Caroline Abernathy, Louise Foster, Andrew Gratrix, Vicky Martinson, Priyai Parkinson, Elizabeth Stones, Llucia Carbral-Ortega, Georgia Bercades, David Brealey, Ingrid Hass, Niall MacCallum, Gladys Martir, Eamon Raith, Anna Reyes, Deborah Smyth, Letizia Zitter, Sarah Benyon, Suzie Marriott, Linda Park, Samantha Keenan, Elizabeth Gordon, Helen Quinn, Kizzy Baines, Lenka Cagova, Adama Fofano, Lucie Garner, Helen Holcombe, Sue Mepham, Alice Michael Mitchell, Lucy Mwaura, Krithivasan Praman, Alain Vuylsteke, Julie Zamikula, Bally Purewal, Vanessa Rivers, Stephanie Bell, Hayley Blakemore, Borislava Borislavova, Beverley Faulkner, Emma Gendall, Elizabeth Goff, Kati Hayes, Matt Thomas, Ruth Worner, Kerry Smith, Deanna Stephens, Louise Mew, Esther Mwaura, Richard Stewart, Felicity Williams, Lynn Wren, Sara-Beth Sutherland, Emily Bevan, Jane Martin, Dawn Trodd, Geoff Watson, Caroline Wrey Brown, Amy Collins, Waqas Khaliq, Estefania Treus Gude, Olugbenga Akinkugbe, Alasdair Bamford, Emily Beech, Holly Belfield, Michael Bell, Charlene Davies, Gareth A.L. Jones, Tara McHugh, Hamza Meghari, Lauran O'Neill, Mark J. Peters, Samiran Ray, Ana Luisa Tomas, Iona Burn, Geraldine Hambrook, Katarina Manso, Ruth Penn, Pradeep Shanmugasundaram, Julie Tebbutt, Danielle Thornton, Jade Cole, Rhys Davies, Donna Duffin, Helen Hill, Ben Player, Emma Thomas, Angharad Williams, Denise Griffin, Nycola Muchenje, Mcdonald Mupudzi, Richard Partridge, Jo-Anna Conyngham, Rachel Thomas, Mary Wright, Maria Alvarez Corral, Reni Jacob, Cathy Jones, Craig Denmade, Sarah Beavis, Katie Dale, Rachel Gascoyne, Joanne Hawes, Kelly Pritchard, Lesley Stevenson, Amanda Whileman, Patricia Doble, Joanne Hutter, Corinne Pawley, Charmaine Shovelton, Marius Vaida, Deborah Butcher, Susie O'Sullivan, Nicola Butterworth-Cowin, Norfaizan Ahmad, Joann Barker, Kris Bauchmuller, Sarah Bird, Kay Cawthron, Kate Harrington, Yvonne Jackson, Faith Kibutu, Becky Lenagh, Shamiso Masuko, Gary H. Mills, Ajay Raithatha, Matthew Wiles, Jayne Willson, Helen Newell, Alison Lye, Lorenza Nwafor, Claire Jarman, Sarah Rowland-Jones, David Foote, Joby Cole, Roger Thompson, James Watson, Lisa Hesseldon, Irene Macharia, Luke Chetam, Jacqui Smith, Amber Ford, Samantha Anderson, Kathryn Birchall, Kay Housley, Sara Walker, Leanne Milner, Helena Hanratty, Helen Trower, Patrick Phillips, Simon Oxspring, Ben Donne, Catherine Jardine, Dewi Williams, Alasdair Hay, Rebecca Flanagan, Gareth Hughes, Scott Latham, Emma McKenna, Jennifer Anderson, Robert Hull, Kat Rhead, Carina Cruz, Natalie Pattison, Rob Charnock, Denise McFarland, Denise Cosgrove, Ashar Ahmed, Anna Morris, Srinivas Jakkula, Asifa Ali, Megan Brady, Sam Dale, Annalisa Dance, Lisa Gledhill, Jill Greig, Kathryn Hanson, Kelly Holdroyd, Marie Home, Diane Kelly, Ross Kitson, Lear Matapure, Deborah Melia, Samantha Mellor, Tonicha Nortcliffe, Jez Pinnell, Matthew Robinson, Lisa Shaw, Ryan Shaw, Lesley Thomis, Alison Wilson, Tracy Wood, Lee-Ann Bayo, Ekta Merwaha, Tahira Ishaq, Sarah Hanley, Meg Hibbert, Dariusz Tetla, Chrsitopher Woodford, Latha Durga, Gareth Kennard-Holden, Debbie Branney, Jordan Frankham, Sally Pitts, Nigel White, Shondipon Laha, Mark Verlander, Alexandra Williams, Abdelhakim Altabaibeh, Ana Alvaro, Kayleigh Gilbert, Louise Ma, Loreta Mostoles, Chetan Parmar, Kathryn Simpson, Champa Jetha, Lauren Booker, Anezka Pratley, Colene Adams, Anita Agasou, Tracie Arden, Amy Bowes, Pauline Boyle, Mandy Beekes, Heather Button, Nigel Capps, Mandy Carnahan, Anne Carter, Danielle Childs, Denise Donaldson, Kelly Hard, Fran Hurford, Yasmin Hussain, Ayesha Javaid, James Jones, Sanal Jose, Michael Leigh, Terry Martin, Helen Millward, Nichola Motherwell, Rachel Rikunenko, Jo Stickley, Julie Summers, Louise Ting, Helen Tivenan, Louise Tonks, Rebecca Wilcox, Maureen Holland, Natalie Keenan, Marc Lyons, Helen Wassall, Chris Marsh, Mervin Mahenthran, Emma Carter, Thomas Kong, Helen Blackman, Ben Creagh-Brown, Sinead Donlon, Natalia Michalak-Glinska, Sheila Mtuwa, Veronika Pristopan, Armorel Salberg, Eleanor Smith, Sarah Stone, Charles Piercy, Jerik Verula, Dorota Burda, Rugia Montaser, Lesley Harden, Irving Mayangao, Cheryl Marriott, Paul Bradley, Celia Harris, Susan Anderson, Eleanor Andrews, Janine Birch, Emma Collins, Kate Hammerton, Ryan O'Leary, Michele Clark, Sarah Purvis, Russell Barber, Claire Hewitt, Annette Hilldrith, Karen Jackson-Lawrence, Sarah Shepardson, Maryanne Wills, Susan Butler, Silvia Tavares, Amy Cunningham, Julia Hindale, Sarwat Arif, Sarah Bean, Karen Burt, Michael Spivey, Carrie Demetriou, Charlotte Eckbad, Sarah Hierons, Lucy Howie, Sarah Mitchard, Lidia Ramos, Alfredo Serrano-Ruiz, Katie White, Fiona Kelly, Daniele Cristiano, Natalie Dormand, Zohreh Farzad, Mahitha Gummadi, Kamal Liyanage, Brijesh Patel, Sara Salmi, Geraldine Sloane, Vicky Thwaites, Mathew Varghese, Anelise C. Zborowski, John Allan, Tim Geary, Gordon Houston, Alistair Meikle, Peter O'Brien, Miranda Forsey, Agilan Kaliappan, Anne Nicholson, Joanne Riches, Mark Vertue, Elizabeth Allan, Kate Darlington, Ffyon Davies, Jack Easton, Sumit Kumar, Richard Lean, Daniel Menzies, Richard Pugh, Xinyi Qiu, Llinos Davies, Hannah Williams, Jeremy Scanlon, Gwyneth Davies, Callum Mackay, Joannne Lewis, Stephanie Rees, Metod Oblak, Monica Popescu, Mini Thankachen, Andrew Higham, Kerry Simpson, Jayne Craig, Rosie Baruah, Sheila Morris, Susie Ferguson, Amy Shepherd, Luke Stephen Prockter Moore, Marcela Paola Vizcaychipi, Laura Gomes de Almeida Martins, Jaime Carungcong, Inthakab Ali Mohamed Ali, Karen Beaumont, Mark Blunt, Zoe Coton, Hollie Curgenven, Mohamed Elsaadany, Kay Fernandes, Sameena Mohamed Ally, Harini Rangarajan, Varun Sarathy, Sivarupan Selvanayagam, Dave Vedage, Matthew White, Mandy Gill, Paul Paul, Valli Ratnam, Sarah Shelton, Inez Wynter, Siobhain Carmody, Valerie Joan Page, Claire Marie Beith, Karen Black, Suzanne Clements, Alan Morrison, Dominic Strachan, Margaret Taylor, Michelle Clarkson, Stuart D'Sylva, Kathryn Norman, Fiona Auld, Joanne Donnachie, Ian Edmond, Lynn Prentice, Nikole Runciman, Dario Salutous, Lesley Symon, Anne Todd, Patricia Turner, Abigail Short, Laura Sweeney, Euan Murdoch, Dhaneesha Senaratne, Michaela Hill, Thogulava Kannan, Wild Laura, Rikki Crawley, Abigail Crew, Mishell Cunningham, Allison Daniels, Laura Harrison, Susan Hope, Ken Inweregbu, Sian Jones, Nicola Lancaster, Jamie Matthews, Alice Nicholson, Gemma Wray, Helen Langton, Rachel Prout, Malcolm Watters, Catherine Novis, Anthony Barron, Ciara Collins, Sundeep Kaul, Heather Passmore, Claire Prendergast, Anna Reed, Paula Rogers, Rajvinder Shokkar, Meriel Woodruff, Hayley Middleton, Oliver Polgar, Claire Nolan, Kanta Mahay, Dawn Collier, Anil Hormis, Victoria Maynard, Cheryl Graham, Rachel Walker, Ellen Knights, Alicia Price, Alice Thomas, Chris Thorpe, Teresa Behan, Caroline Burnett, Jonathan Hatton, Elaine Heeney, Atideb Mitra, Maria Newton, Rachel Pollard, Rachael Stead, Vishal Amin, Elena Anastasescu, Vikram Anumakonda, Komala Karthik, Rizwana Kausar, Karen Reid, Jacqueline Smith, Janet Imeson-Wood, Denise Skinner, Jane Gaylard, Dee Mullan, Julie Newman, Alison Brown, Vikki Crickmore, Gabor Debreceni, Joy Wilkins, Liz Nicol, Rosie Reece-Anthony, Mark Birt, Alison Ghosh, Emma Williams, Louise Allen, Eva Beranova, Nikki Crisp, Joanne Deery, Tracy Hazelton, Alicia Knight, Carly Price, Sorrell Tilbey, Salah Turki, Sharon Turney, Joshua Cooper, Cheryl Finch, Sarah Liderth, Alison Quinn, Natalia Waddington, Tina Coventry, Susan Fowler, Michael MacMahon, Amanda McGregor, Anne Cowley, Judith Highgate, Jane Gregory, Susan O'Connell, Tim Smith, Luigi Barberis, Shameer Gopal, Nichola Harris, Victoria Lake, Stella Metherell, Elizabeth Radford, Amelia Daniel, Joanne Finn, Rajnish Saha, Nikki White, Phil Donnison, Fiona Trim, Beena Eapen, Jenny Birch, Laura Bough, Josie Goodsell, Rebecca Tutton, Patricia Williams, Sarah Williams, Barbara Winter-Goodwin, Ailstair Nichol, Kathy Brickell, Michelle Smyth, Lorna Murphy, Samantha Coetzee, Alistair Gales, Igor Otahal, Meena Raj, Craig Sell, Paula Hilltout, Jayne Evitts, Amanda Tyler, Joanne Waldron, Kate Beesley, Sarah Board, Agnieszka Kubisz-Pudelko, Alison Lewis, Jess Perry, Lucy Pippard, Di Wood, Clare Buckley, Peter Barry, Neil Flint, Patel Rekha, Dawn Hales, Lara Bunni, Claire Jennings, Monica Latif, Rebecca Marshall, Gayathri Subramanian, Peter J. McGuigan, Christopher Wasson, Stephanie Finn, Jackie Green, Erin Collins, Bernadette King, Andy Campbell, Sara Smuts, Joseph Duffield, Oliver Smith, Lewis Mallon, Watkins Claire, Liam Botfield, Joanna Butler, Catherine Dexter, Jo Fletcher, Atul Garg, Aditya Kuravi, Poonam Ranga, Emma Virgilio, Zakaula Belagodu, Bridget Fuller, Anca Gherman, Olumide Olufuwa, Remi Paramsothy, Carmel Stuart, Naomi Oakley, Charlotte Kamundi, David Tyl, Katy Collins, Pedro Silva, June Taylor, Laura King, Charlotte Coates, Maria Crowley, Phillipa Wakefield, Jane Beadle, Laura Johnson, Janet Sargeant, Madeleine Anderson, Ailbhe Brady, Rebekah Chan, Jeff Little, Shane McIvor, Helena Prady, Helen Whittle, Bijoy Mathew, Ben Attwood, Penny Parsons, Geraldine Ward, Pamela Bremmer, West Joe, Baird Tracy, Ruddy Jim, Ellie Davies, Sonia Sathe, Catherine Dennis, Alastair McGregor, Victoria Parris, Sinduya Srikaran, Anisha Sukha, Noreen Clarke, Jonathan Whiteside, Mairi Mascarenhas, Avril Donaldson, Joanna Matheson, Fiona Barrett, Marianne O'Hara, Laura Okeefe, Clare Bradley, Christine Eastgate-Jackson, Helder Filipe, Daniel Martin, Amitaa Maharajh, Sara Mingo Garcia, Glykeria Pakou, Mark De Neef, Kathy Dent, Elizabeth Horsley, Muhmmad Nauman Akhtar, Sandra Pearson, Dorota Potoczna, Sue Spencer, Melanie Clapham, Rosemary Harper, Una Poultney, Polly Rice, Rachel Mutch, Lisa Armstrong, Hayley Bates, Emma Dooks, Fiona Farquhar, Brigid Hairsine, Chantal McParland, Sophie Packham, Rehana Bi, Barney Scholefield, Lydia Ashton, Linsha George, Sophie Twiss, David Wright, Manish Chablani, Amy Kirkby, Kimberley Netherton, Kim Davies, Linda O'Brien, Zohra Omar, Emma Perkins, Tracy Lewis, Isobel Sutherland, Karen Burns, Dr Ben Chandler, Kerry Elliott, Janine Mallinson, Alison Turnbull, Prisca Gondo, Bernard Hadebe, Abdul Kayani, Bridgett Masunda, Taya Anderson, Dan Hawcutt, Laura O'Malley, Laura Rad, Naomi Rogers, Paula Saunderson, Kathryn Sian Allison, Deborah Afolabi, Jennifer Whitbread, Dawn Jones, Rachael Dore, Matthew Halkes, Pauline Mercer, Lorraine Thornton, Joy Dawson, Sweyn Garrioch, Melanie Tolson, Jonathan Aldridge, Ritoo Kapoor, David Loader, Karen Castle, Sally Humphreys, Ruth Tampsett, Katherine Mackintosh, Amanda Ayers, Wendy Harrison, Julie North, Suzanne Allibone, Roman Genetu, Vidya Kasipandian, Amit Patel, Ainhi Mac, Anthony Murphy, Parisa Mahjoob, Roonak Nazari, Lucy Worsley, Andrew Fagan, Thomas Bemand, Ethel Black, Arnold Dela Rosa, Ryan Howle, Shaman Jhanji, Ravishankar Rao Baikady, Kate Colette Tatham, Benjamin Thomas, Dina Bell, Rosalind Boyle, Katie Douglas, Lynn Glass, Emma Lee, Liz Lennon, Austin Rattray, Abigail Taylor, Rachel Anne Hughes, Helen Thomas, Alun Rees, Michaela Duskova, Janet Phipps, Suzanne Brooks, Michelle Edwards, Sheena Quaid, Ekaterina Watson, Adam Brayne, Emma Fisher, Jane Hunt, Peter Jackson, Duncan Kaye, Nicholas Love, Juliet Parkin, Victoria Tuckey, Lynne Van Koutrik, Sasha Carter, Benedict Andrew, Louise Findlay, Katie Adams, Jen Service, Alison Williams, Claire Cheyne, Anne Saunderson, Sam Moultrie, Miranda Odam, Kathryn Hall, Isheunesu Mapfunde, Charlotte Willis, Alex Lyon, Chunda Sri-Chandana, Joslan Scherewode, Lorraine Stephenson, Sarah Marsh, John Hardy, Henry Houlden, Eleanor Moncur, Ambreen Tariq, Arianna Tucci, Maria Hobrok, Ronda Loosley, Heather McGuinness, Helen Tench, Rebecca Wolf-Roberts, Val Irvine, Benjamin Shelley, Claire Gorman, Abhinav Gupta, Elizabeth Timlick, Rebecca Brady, Barry Milligan, Arianna Bellini, Jade Bryant, Anton Mayer, Amy Pickard, Nicholas Roe, Jason Sowter, Alex Howlett, Katy Fidler, Emma Tagliavini, and Kevin Donnelly

Subjects
SARS-CoV-2, host genetics, toll-like receptor 7, targeted sequencing, rare variants, variant collapsing analysis, Genetics, QH426-470
Abstract

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Published
2024
Full Text
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2. Exploring the Experiences of Family Members When a Patient Is Admitted to the ICU with a Severe Traumatic Brain Injury: A Scoping Review

Author

Kati Hayes, Sam Harding, Kirsten Buckley, Bronagh Blackwood, and Jos M. Latour

Subjects
severe traumatic brain injury, family members, caregivers, intensive care, critical care, scoping review, Medicine
Abstract

The needs of family members of patients in the intensive care unit (ICU) with a severe traumatic brain injury (TBI) remain unmet. To date, no review has been performed to explore the experiences of relatives of adults who have been admitted to the ICU for treatment of a TBI. The aim of this scoping review is to explore and map the evidence of the experiences of family members when an adult relative is admitted to an ICU with a severe TBI. This review follows a combination of guidelines from Arksey and O’Malley and the Joanna Briggs Institute. Five electronic databases, Medline, Emcare, Embase, CINAHL, and PsycInfo were searched in February 2023, as were a number of grey literature sources. The population, concepts, and context framework were used to define the inclusion and exclusion criteria. From 4077 records, nine studies were retained, which represented seven discrete studies. The experiences of family members were thematically analyzed. The narrative synthesis of findings revealed three themes: communication with the clinical team, uncertainty, and involvement in care. These results offer richness and depth of understanding to clinicians regarding the experiences of families during this traumatic time. This review provides direction for targeted interventions aimed at supporting family members while in the ICU.

Published
2023
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3. Early intravenous Beta-Blockade with esmolol in adults with isolated severe Traumatic Brain Injury (EBB-TBI): protocol for a phase 2a intervention design study

Author

Matt Thomas, Kati Hayes, Paul White, Aravind Ramesh, Lucy Culliford, Gareth Ackland, and Anthony Pickering

Abstract

Traumatic brain injury is a leading cause of death and disability worldwide. Interventions that mitigate secondary brain injury have the potential to improve outcomes for patients and reduce the impact on communities and society. Increased circulating catecholamines are associated with worse outcomes and there is supportive animal data and indications in human studies of benefit from beta-blockade after severe traumatic brain injury. Here we present the protocol for a dose-finding study using esmolol in adults commenced within 24 hours of severe traumatic brain injury. Esmolol has practical advantages and theoretical benefits as a neuroprotective agent in this setting, but these must be balanced against the known risk of secondary injury from hypotension. The aim of this study is to determine a dose schedule for esmolol, using the continual reassessment method, that combines a clinically significant reduction in heart rate as a surrogate for catecholamine drive with maintenance of cerebral perfusion pressure. The maximum tolerated dosing schedule for esmolol can then be tested for patient benefit in subsequent randomised controlled trials.

Published
2023

4. Coenzyme Q10 supplementation in traumatic brain injury: a scoping review protocol

Author

Kaylee Allan, Katie Barnard, Matthew Thomas, and Kati Hayes

Subjects
Male, medicine.medical_specialty, Traumatic brain injury, Ubiquinone, Population, MEDLINE, Context (language use), Cochrane Library, law.invention, chemistry.chemical_compound, Randomized controlled trial, law, Brain Injuries, Traumatic, medicine, Humans, education, Intensive care medicine, General Nursing, Coenzyme Q10, education.field_of_study, Clinical Trials as Topic, business.industry, Clinical study design, Brain, General Medicine, Vitamins, medicine.disease, Oxidative Stress, Review Literature as Topic, Treatment Outcome, chemistry, Research Design, Dietary Supplements, Female, business
Abstract

Objective The objective of this review is to map evidence on coenzyme Q10 (CoQ10) use in traumatic brain injury (TBI). Introduction Traumatic brain injury is an insult to the brain structure caused by external force and resulting in physiological disruption to brain function. Globally, 60% of all TBIs occur from road traffic accidents. In 2016, the World Health Organization reported that road traffic accidents were among the top 10 leading causes of death. Following the initial brain injury, a secondary injury can occur due primarily to a significant increase in production of free radicals causing oxidative stress, which can dictate the patient's ability to survive. Coenzyme Q10 is known to protect neuronal cells from oxidative stress; the mechanism for this has been examined in studies using rats. This review will examine what is known about CoQ10 in TBI and identify gaps in the literature, which may guide future research. Inclusion criteria The review will include both human and animal subjects who have experienced a TBI in the acute/laboratory-controlled setting and where CoQ10 is supplemented. Animal studies will be included. The review will consider experimental and quasi-experimental study designs including randomized controlled trials, non-randomized controlled trials, before and after studies, and interrupted time-series studies. Studies published in English will be considered, with no date restriction. Methods Searches will be conducted in the Cochrane Library, MEDLINE, Embase, CINAHL and trial registries. Data will be extracted and presented on details about the population, concept, context, study methods and key findings.

Published
2019

5. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19

Author

Angus, Derek, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa, Horvat, Christopher, Hullegie, Sebastiaan, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, Mcauley, Daniel, Mcglothin, Anna, Mcguinness, Shay, Mcverry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger, Mcarthur, Colin, Webb, Steven, Gordon, Anthony, NIHR, Hôpital Raymond Poincaré [AP-HP], Writing Committee for the REMAP-CAP Investigators, Farah Al-Beidh, Derek Angus, Djillali Annane, Yaseen Arabi, Wilma van Bentum-Puijk, Scott Berry, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Meredith Buxton, Allen Cheng, Menno De Jong, Lennie Derde, Lise Estcourt, Herman Goossens, Anthony Gordon, Cameron Green, Rashan Haniffa, Francois Lamontagne, Patrick Lawler, Edward Litton, John Marshall, Colin McArthur, Daniel McAuley, Shay McGuinness, Bryan McVerry, Stephanie Montgomery, Paul Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Kathryn Rowan, Christopher Seymour, Anne Turner, Frank van de Veerdonk, Steve Webb, Ryan Zarychanski, Lewis Campbell, Andrew Forbes, David Gattas, Stephane Heritier, Lisa Higgins, Peter Kruger, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Paul Young, Sean Bagshaw, Nick Daneman, Niall Ferguson, Cheryl Misak, Marlene Santos, Sebastiaan Hullegie, Mathias Pletz, Gernot Rohde, Kathy Rowan, Brian Alexander, Kim Basile, Timothy Girard, Christopher Horvat, David Huang, Kelsey Linstrum, Jennifer Vates, Richard Beasley, Robert Fowler, Steve McGloughlin, Susan Morpeth, David Paterson, Bala Venkatesh, Tim Uyeki, Kenneth Baillie, Eamon Duffy, Rob Fowler, Thomas Hills, Katrina Orr, Asad Patanwala, Steve Tong, Mihai Netea, Shilesh Bihari, Marc Carrier, Dean Fergusson, Ewan Goligher, Ghady Haidar, Beverley Hunt, Anand Kumar, Mike Laffan, Patrick Lawless, Sylvain Lother, Peter McCallum, Saskia Middeldopr, Zoe McQuilten, Matthew Neal, John Pasi, Roger Schutgens, Simon Stanworth, Alexis Turgeon, Alexandra Weissman, Neill Adhikari, Matthew Anstey, Emily Brant, Angelique de Man, Francois Lamonagne, Marie-Helene Masse, Andrew Udy, Donald Arnold, Phillipe Begin, Richard Charlewood, Michael Chasse, Mark Coyne, Jamie Cooper, James Daly, Iain Gosbell, Heli Harvala-Simmonds, Tom Hills, Sheila MacLennan, David Menon, John McDyer, Nicole Pridee, David Roberts, Manu Shankar-Hari, Helen Thomas, Alan Tinmouth, Darrell Triulzi, Tim Walsh, Erica Wood, Carolyn Calfee, Cecilia O’Kane, Murali Shyamsundar, Pratik Sinha, Taylor Thompson, Ian Young, Shailesh Bihari, Carol Hodgson, John Laffey, Danny McAuley, Neil Orford, Ary Neto, Michelle Detry, Mark Fitzgerald, Roger Lewis, Anna McGlothlin, Ashish Sanil, Christina Saunders, Lindsay Berry, Elizabeth Lorenzi, Eliza Miller, Vanessa Singh, Claire Zammit, Wilma van Bentum Puijk, Wietske Bouwman, Yara Mangindaan, Lorraine Parker, Svenja Peters, Ilse Rietveld, Kik Raymakers, Radhika Ganpat, Nicole Brillinger, Rene Markgraf, Kate Ainscough, Kathy Brickell, Aisha Anjum, Janis-Best Lane, Alvin Richards-Belle, Michelle Saull, Daisy Wiley, Julian Bion, Jason Connor, Simon Gates, Victoria Manax, Tom van der Poll, John Reynolds, Marloes van Beurden, Evelien Effelaar, Joost Schotsman, Craig Boyd, Cain Harland, Audrey Shearer, Jess Wren, Giles Clermont, William Garrard, Kyle Kalchthaler, Andrew King, Daniel Ricketts, Salim Malakoutis, Oscar Marroquin, Edvin Music, Kevin Quinn, Heidi Cate, Karen Pearson, Joanne Collins, Jane Hanson, Penny Williams, Shane Jackson, Adeeba Asghar, Sarah Dyas, Mihaela Sutu, Sheenagh Murphy, Dawn Williamson, Nhlanhla Mguni, Alison Potter, David Porter, Jayne Goodwin, Clare Rook, Susie Harrison, Hannah Williams, Hilary Campbell, Kaatje Lomme, James Williamson, Jonathan Sheffield, Willian van’t Hoff, Phobe McCracken, Meredith Young, Jasmin Board, Emma Mart, Cameron Knott, Julie Smith, Catherine Boschert, Julia Affleck, Mahesh Ramanan, Ramsy D’Souza, Kelsey Pateman, Arif Shakih, Winston Cheung, Mark Kol, Helen Wong, Asim Shah, Atul Wagh, Joanne Simpson, Graeme Duke, Peter Chan, Brittney Cartner, Stephanie Hunter, Russell Laver, Tapaswi Shrestha, Adrian Regli, Annamaria Pellicano, James McCullough, Mandy Tallott, Nikhil Kumar, Rakshit Panwar, Gail Brinkerhoff, Cassandra Koppen, Federica Cazzola, Matthew Brain, Sarah Mineall, Roy Fischer, Vishwanath Biradar, Natalie Soar, Hayden White, Kristen Estensen, Lynette Morrison, Joanne Smith, Melanie Cooper, Monash Health, Yahya Shehabi, Wisam Al-Bassam, Amanda Hulley, Christina Whitehead, Julie Lowrey, Rebecca Gresha, James Walsham, Jason Meyer, Meg Harward, Ellen Venz, Patricia Williams, Catherine Kurenda, Kirsy Smith, Margaret Smith, Rebecca Garcia, Deborah Barge, Deborah Byrne, Kathleen Byrne, Alana Driscoll, Louise Fortune, Pierre Janin, Elizabeth Yarad, Naomi Hammond, Frances Bass, Angela Ashelford, Sharon Waterson, Steve Wedd, Robert McNamara, Heidi Buhr, Jennifer Coles, Sacha Schweikert, Bradley Wibrow, Rashmi Rauniyar, Erina Myers, Ed Fysh, Ashlish Dawda, Bhaumik Mevavala, Ed Litton, Janet Ferrier, Priya Nair, Hergen Buscher, Claire Reynolds, John Santamaria, Leanne Barbazza, Jennifer Homes, Roger Smith, Lauren Murray, Jane Brailsford, Loretta Forbes, Teena Maguire, Vasanth Mariappa, Judith Smith, Scott Simpson, Matthew Maiden, Allsion Bone, Michelle Horton, Tania Salerno, Martin Sterba, Wenli Geng, Pieter Depuydt, Jan De Waele, Liesbet De Bus, Jan Fierens, Stephanie Bracke, Brenda Reeve, William Dechert, Michaël Chassé, François Martin Carrier, Dounia Boumahni, Fatna Benettaib, Ali Ghamraoui, David Bellemare, Ève Cloutier, Charles Francoeur, François Lamontagne, Frédérick D’Aragon, Elaine Carbonneau, Julie Leblond, Gloria Vazquez-Grande, Nicole Marten, Maggie Wilson, Martin Albert, Karim Serri, Alexandros Cavayas, Mathilde Duplaix, Virginie Williams, Bram Rochwerg, Tim Karachi, Simon Oczkowski, John Centofanti, Tina Millen, Erick Duan, Jennifer Tsang, Lisa Patterson, Shane English, Irene Watpool, Rebecca Porteous, Sydney Miezitis, Lauralyn McIntyre, Laurent Brochard, Karen Burns, Gyan Sandhu, Imrana Khalid, Alexandra Binnie, Elizabeth Powell, Alexandra McMillan, Tracy Luk, Noah Aref, Zdravko Andric, Sabina Cviljevic, Renata Đimoti, Marija Zapalac, Gordan Mirković, Bruno Baršić, Marko Kutleša, Viktor Kotarski, Ana Vujaklija Brajković, Jakša Babel, Helena Sever, Lidija Dragija, Ira Kušan, Suvi Vaara, Leena Pettilä, Jonna Heinonen, Anne Kuitunen, Sari Karlsson, Annukka Vahtera, Heikki Kiiski, Sanna Ristimäki, Amine Azaiz, Cyril Charron, Mathieu Godement, Guillaume Geri, Antoine Vieillard-Baron, Franck Pourcine, Mehran Monchi, David Luis, Romain Mercier, Anne Sagnier, Nathalie Verrier, Cecile Caplin, Shidasp Siami, Christelle Aparicio, Sarah Vautier, Asma Jeblaoui, Muriel Fartoukh, Laura Courtin, Vincent Labbe, Cécile Leparco, Grégoire Muller, Mai-Anh Nay, Toufik Kamel, Dalila Benzekri, Sophie Jacquier, Emmanuelle Mercier, Delphine Chartier, Charlotte Salmon, PierreFrançois Dequin, Francis Schneider, Guillaume Morel, Sylvie L’Hotellier, Julio Badie, Fernando Daniel Berdaguer, Sylvain Malfroy, Chaouki Mezher, Charlotte Bourgoin, Bruno Megarbane, Sebastian Voicu, Nicolas Deye, Isabelle Malissin, Laetitia Sutterlin, Christophe Guitton, Cédric Darreau, Mickaël Landais, Nicolas Chudeau, Alain Robert, Pierre Moine, Nicholas Heming, Virginie Maxime, Isabelle Bossard, Tiphaine Barbarin Nicholier, Gwenhael Colin, Vanessa Zinzoni, Natacham Maquigneau, André Finn, Gabriele Kreß, Uwe Hoff, Carl Friedrich Hinrichs, Jens Nee, Mathias Pletz, Stefan Hagel, Juliane Ankert, Steffi Kolanos, Frank Bloos, Sirak Petros, Bastian Pasieka, Kevin Kunz, Peter Appelt, Bianka Schütze, Stefan Kluge, Axel Nierhaus, Dominik Jarczak, Kevin Roedl, Dirk Weismann, Anna Frey, Vivantes Klinikum Neukölln, Lorenz Reill, Michael Distler, Astrid Maselli, János Bélteczki, István Magyar, Ágnes Fazekas, Sándor Kovács, Viktória Szőke, Gábor Szigligeti, János Leszkoven, Daniel Collins, Patrick Breen, Stephen Frohlich, Ruth Whelan, Bairbre McNicholas, Michael Scully, Siobhan Casey, Maeve Kernan, Peter Doran, Michael O’Dywer, Michelle Smyth, Leanne Hayes, Oscar Hoiting, Marco Peters, Els Rengers, Mirjam Evers, Anton Prinssen, Jeroen Bosch Ziekenhuis, Koen Simons, Wim Rozendaal, F Polderman, P de Jager, M Moviat, A Paling, A Salet, Emma Rademaker, Anna Linda Peters, E de Jonge, J Wigbers, E Guilder, M Butler, Keri-Anne Cowdrey, Lynette Newby, Yan Chen, Catherine Simmonds, Rachael McConnochie, Jay Ritzema Carter, Seton Henderson, Kym Van Der Heyden, Jan Mehrtens, Tony Williams, Alex Kazemi, Rima Song, Vivian Lai, Dinu Girijadevi, Robert Everitt, Robert Russell, Danielle Hacking, Ulrike Buehner, Erin Williams, Troy Browne, Kate Grimwade, Jennifer Goodson, Owen Keet, Owen Callender, Robert Martynoga, Kara Trask, Amelia Butler, Livia Schischka, Chelsea Young, Eden Lesona, Shaanti Olatunji, Yvonne Robertson, Nuno José, Teodoro Amaro dos Santos Catorze, Tiago Nuno Alfaro de Lima Pereira, Lucilia Maria Neves Pessoa, Ricardo Manuel Castro Ferreira, Joana Margarida Pereira Sousa Bastos, Simin Aysel Florescu, Delia Stanciu, Miahela Florentina Zaharia, Alma Gabriela Kosa, Daniel Codreanu, Yaseen Marabi, Eman Al Qasim, Mohamned Moneer Hagazy, Lolowa Al Swaidan, Hatim Arishi, Rosana Muñoz-Bermúdez, Judith Marin-Corral, Anna Salazar Degracia, Francisco Parrilla Gómez, Maria Isabel Mateo López, Jorge Rodriguez Fernandez, Sheila Cárcel Fernández, Rosario Carmona Flores, Rafael León López, Carmen de la Fuente Martos, Angela Allan, Petra Polgarova, Neda Farahi, Stephen McWilliam, Daniel Hawcutt, Laura Rad, Laura O’Malley, Jennifer Whitbread, Olivia Kelsall, Laura Wild, Jessica Thrush, Hannah Wood, Karen Austin, Adrian Donnelly, Martin Kelly, Sinéad O’Kane, Declan McClintock, Majella Warnock, Paul Johnston, Linda Jude Gallagher, Clare Mc Goldrick, Moyra Mc Master, Anna Strzelecka, Rajeev Jha, Michael Kalogirou, Christine Ellis, Vinodh Krishnamurthy, Vashish Deelchand, Jon Silversides, Peter McGuigan, Kathryn Ward, Aisling O’Neill, Stephanie Finn, Barbara Phillips, Dee Mullan, Laura Oritz-Ruiz de Gordoa, Matthew Thomas, Katie Sweet, Lisa Grimmer, Rebekah Johnson, Jez Pinnell, Matt Robinson, Lisa Gledhill, Tracy Wood, Matt Morgan, Jade Cole, Helen Hill, Michelle Davies, David Antcliffe, Maie Templeton, Roceld Rojo, Phoebe Coghlan, Joanna Smee, Euan Mackay, Jon Cort, Amanda Whileman, Thomas Spencer, Nick Spittle, Vidya Kasipandian, Amit Patel, Suzanne Allibone, Roman Mary Genetu, Mohamed Ramali, Alison Ghosh, Peter Bamford, Emily London, Kathryn Cawley, Maria Faulkner, Helen Jeffrey, Tim Smith, Chris Brewer, Jane Gregory, James Limb, Amanda Cowton, Julie O’Brien, Nikitas Nikitas, Colin Wells, Liana Lankester, Mark Pulletz, Patricia Williams, Jenny Birch, Sophie Wiseman, Sarah Horton, Ana Alegria, Salah Turki, Tarek Elsefi, Nikki Crisp, Louise Allen, Iain McCullagh, Philip Robinson, Carole Hays, Maite Babio-Galan, Hannah Stevenson, Divya Khare, Meredith Pinder, Selvin Selvamoni, Amitha Gopinath, Richard Pugh, Daniel Menzies, Callum Mackay, Elizabeth Allan, Gwyneth Davies, Kathryn Puxty, Claire McCue, Susanne Cathcart, Naomi Hickey, Jane Ireland, Hakeem Yusuff, Graziella Isgro, Chris Brightling, Michelle Bourne, Michelle Craner, Malcolm Watters, Rachel Prout, Louisa Davies, Suzannah Pegler, Lynsey Kyeremeh, Gill Arbane, Karen Wilson, Linda Gomm, Federica Francia, Stephen Brett, Sonia Sousa Arias, Rebecca Elin Hall, Joanna Budd, Charlotte Small, Janine Birch, Emma Collins, Jeremy Henning, Stephen Bonner, Keith Hugill, Emanuel Cirstea, Dean Wilkinson, Michal Karlikowski, Helen Sutherland, Elva Wilhelmsen, Jane Woods, Julie North, Dhinesh Sundaran, Laszlo Hollos, Susan Coburn, Joanne Walsh, Margaret Turns, Phil Hopkins, John Smith, Harriet Noble, Maria Theresa Depante, Emma Clarey, Shondipon Laha, Mark Verlander, Alexandra Williams, Abby Huckle, Andrew Hall, Jill Cooke, Caroline Gardiner-Hill, Carolyn Maloney, Hafiz Qureshi, Neil Flint, Sarah Nicholson, Sara Southin, Andrew Nicholson, Barbara Borgatta, Ian Turner-Bone, Amie Reddy, Laura Wilding, Loku Chamara Warnapura, Ronan Agno Sathianathan, David Golden, Ciaran Hart, Jo Jones, Jonathan Bannard-Smith, Joanne Henry, Katie Birchall, Fiona Pomeroy, Rachael Quayle, Arystarch Makowski, Beata Misztal, Iram Ahmed, Thyra KyereDiabour, Kevin Naiker, Richard Stewart, Esther Mwaura, Louise Mew, Lynn Wren, Felicity Willams, Richard Innes, Patricia Doble, Joanne Hutter, Charmaine Shovelton, Benjamin Plumb, Tamas Szakmany, Vincent Hamlyn, Nancy Hawkins, Sarah Lewis, Amanda Dell, Shameer Gopal, Saibal Ganguly, Andrew Smallwood, Nichola Harris, Stella Metherell, Juan Martin Lazaro, Tabitha Newman, Simon Fletcher, Jurgens Nortje, Deirdre Fottrell-Gould, Georgina Randell, Mohsin Zaman, Einas Elmahi, Andrea Jones, Kathryn Hall, Gary Mills, Kim Ryalls, Helen Bowler, Jas Sall, Richard Bourne, Zoe Borrill, Tracey Duncan, Thomas Lamb, Joanne Shaw, Claire Fox, Jeronimo Moreno Cuesta, Kugan Xavier, Dharam Purohit, Munzir Elhassan, Dhanalakshmi Bakthavatsalam, Matthew Rowland, Paula Hutton, Archana Bashyal, Neil Davidson, Clare Hird, Manish Chhablani, Gunjan Phalod, Amy Kirkby, Simon Archer, Kimberley Netherton, Henrik Reschreiter, Julie Camsooksai, Sarah Patch, Sarah Jenkins, David Pogson, Steve Rose, Zoe Daly, Lutece Brimfield, Helen Claridge, Dhruv Parekh, Colin Bergin, Michelle Bates, Joanne Dasgin, Christopher McGhee, Malcolm Sim, Sophie Kennedy Hay, Steven Henderson, Mandeep-Kaur Phull, Abbas Zaidi, Tatiana Pogreban, Lace Paulyn Rosaroso, Daniel Harvey, Benjamin Lowe, Megan Meredith, Lucy Ryan, Anil Hormis, Rachel Walker, Dawn Collier, Sarah Kimpton, Susan Oakley, Kevin Rooney, Natalie Rodden, Emma Hughes, Nicola Thomson, Deborah McGlynn, Andrew Walden, Nicola Jacques, Holly Coles, Emma Tilney, Emma Vowell, Martin Schuster-Bruce, Sally Pitts, Rebecca Miln, Laura Purandare, Luke Vamplew, Michael Spivey, Sarah Bean, Karen Burt, Lorraine Moore, Christopher Day, Charly Gibson, Elizabeth Gordon, Letizia Zitter, Samantha Keenan, Evelyn Baker, Shiney Cherian, Sean Cutler, Anna Roynon-Reed, Kate Harrington, Ajay Raithatha, Kris Bauchmuller, Norfaizan Ahmad, Irina Grecu, Dawn Trodd, Jane Martin, Caroline Wrey Brown, Ana-Marie Arias, Thomas Craven, David Hope, Jo Singleton, Sarah Clark, Nicola Rae, Ingeborg Welters, David Oliver Hamilton, Karen Williams, Victoria Waugh, David Shaw, Zudin Puthucheary, Timothy Martin, Filipa Santos, Ruzena Uddin, Alastair Somerville, Kate Colette Tatham, Shaman Jhanji, Ethel Black, Arnold Dela Rosa, Ryan Howle, Redmond Tully, Andrew Drummond, Joy Dearden, Jennifer Philbin, Sheila Munt, Alain Vuylsteke, Charles Chan, Saji Victor, Ramprasad Matsa, Minerva Gellamucho, Ben Creagh-Brown, Joe Tooley, Laura Montague, Fiona De Beaux, Laetitia Bullman, Ian Kersiake, Carrie Demetriou, Sarah Mitchard, Lidia Ramos, Katie White, Phil Donnison, Maggie Johns, Ruth Casey, Lehentha Mattocks, Sarah Salisbury, Paul Dark, Andrew Claxton, Danielle McLachlan, Kathryn Slevin, Stephanie Lee, Jonathan Hulme, Sibet Joseph, Fiona Kinney, Ho Jan Senya, Aneta Oborska, Abdul Kayani, Bernard Hadebe, Rajalakshmi Orath Prabakaran, Lesley Nichols, Matt Thomas, Ruth Worner, Beverley Faulkner, Emma Gendall, Kati Hayes, Colin Hamilton-Davies, Carmen Chan, Celina Mfuko, Hakam Abbass, Vineela Mandadapu, Susannah Leaver, Daniel Forton, Kamal Patel, Elankumaran Paramasivam, Matthew Powell, Richard Gould, Elizabeth Wilby, Clare Howcroft, Dorota Banach, Ziortza Fernández de Pinedo Artaraz, Leilani Cabreros, Ian White, Maria Croft, Nicky Holland, Rita Pereira, Ahmed Zaki, David Johnson, Matthew Jackson, Hywel Garrard, Vera Juhaz, Alistair Roy, Anthony Rostron, Lindsey Woods, Sarah Cornell, Suresh Pillai, Rachel Harford, Tabitha Rees, Helen Ivatt, Ajay Sundara Raman, Miriam Davey, Kelvin Lee, Russell Barber, Manish Chablani, Farooq Brohi, Vijay Jagannathan, Michele Clark, Sarah Purvis, Bill Wetherill, Ahilanandan Dushianthan, Rebecca Cusack, Kim de Courcy-Golder, Simon Smith, Susan Jackson, Ben Attwood, Penny Parsons, Valerie Page, Xiao Bei Zhao, Deepali Oza, Jonathan Rhodes, Tom Anderson, Sheila Morris, Charlotte Xia Le Tai, Amy Thomas, Alexandra Keen, Stephen Digby, Nicholas Cowley, Laura Wild, David Southern, Harsha Reddy, Andy Campbell, Claire Watkins, Sara Smuts, Omar Touma, Nicky Barnes, Peter Alexander, Tim Felton, Susan Ferguson, Katharine Sellers, Joanne Bradley-Potts, David Yates, Isobel Birkinshaw, Kay Kell, Nicola Marshall, Lisa Carr-Knott, Charlotte Summers, and Mégarbane, Bruno

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, General Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Writing Committee for the REMAP-CAP Investigators, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, General & Internal Medicine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 11 Medical and Health Sciences
Abstract

Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Published
2020

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