Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Authors: Rachael A Evans, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish McAuley, A Shikotra, Amisha Singapuri, Marco Sereno, Ruth Saunders, Victoria Harris, Linzy Houchen‐Wolloff, Raminder Aul, Paul Beirne, Charlotte E. Bolton, Jeremy Brown, Gourab Choudhury, N Diar-Bakerly, Nicholas Easom, Carlos Echevarria, Jonathan Fuld, Nicholas Hart, John R. Hurst, Mark G. Jones, Dhruv Parekh, Paul Pfeffer, Najib M. Rahman, Sarah Rowland‐Jones, Aarti Shah, Dan Wootton, Trudie Chalder, Matthew Davies, Anthony De Soyza, J R Geddes, William Greenhalf, Neil Greening, Liam G. Heaney, Simon Heller, Luke Howard, Joseph Jacob, Gísli Jenkins, Janet M. Lord, William D‐C Man, Gerry P McCann, Stefan Neubauer, Peter Openshaw, Joanna C. Porter, Matthew Rowland, J. T. Scott, Malcolm G. Semple, Sally Singh, David Thomas, Mark Toshner, Keir Lewis, Ryan S. Thwaites, Andrew Briggs, Annemarie B Docherty, S Kerr, Nazir Lone, Jennifer K Quint, Aziz Sheikh, Mathew Thorpe, Bang Zheng, James D. Chalmers, Ling‐Pei Ho, Alex Horsley, Michael Marks, K Poinasamy, Betty Raman, Ewen M. Harrison, Louise V. Wain, Christopher E. Brightling, Kathryn M. Abel, Huzaifa Adamali, Davies Adeloye, O Adeyemi, R Adrego, L A Aguilar Jimenez, Shazaad Ahmad, Nafees Haider, Rizwan Ahmed, N Ahwireng, Mark Ainsworth, B Al-Sheklly, A Alamoudi, Mohammad Ali, M Aljaroof, AM All, Louise Allan, R Allen, L. Allerton, Lynne Allsop, P. Almeida, Doris Altmann, Maria Alvarez Corral, S Amoils, Debra Anderson, Chrystalina A. Antoniades, G Arbane, A. Arias, Chérie Armour, Lará Armstrong, Natalie Armstrong, David Arnold, H Arnold, Abdul Ashish, Andrew Ashworth, Mark Ashworth, S Aslani, H Assefa-Kebede, Catherine Atkin, Philip A. Atkin, Htin Aung, Luke Austin, Cristina Avram, A Ayoub, Marta Babores, Rob Baggott, J. Bagshaw, David Baguley, L. Charles Bailey, J. Kenneth Baillie, S. Bain, M Bakali, M Bakau, Eileen Baldry, David Baldwin, Clive Ballard, Amitava Banerjee, B. Bang, Ruth E Barker, L Barman, Shaney Barratt, Fiona Barrett, D Basire, N Basu, M. Bates, Andrew Bates, Rachel L. Batterham, Helen Baxendale, Hannah Bayes, Michael Beadsworth, P Beckett, M. Beggs, M Begum, D Bell, Robert M. Bell, Katherine Bennett, Eva Beranová, Areti Bermperi, A Berridge, Colin Berry, Sarah Betts, Emily Bevan, Kam Bhui, M Bingham, K Birchall, Lisa Bishop, Karen Bisnauthsing, J Blaikely, Angela Bloss, A Bolger, James Bonnington, A Botkai, C Bourne, Michelle Bourne, Kate Bramham, L Brear, Gerome Breen, J Breeze, E Bright, Simon Brill, Khara Croswaite Brindle, L. Broad, A Broadley, C Brookes, Matthew R. Broome, A. Brown, A. Brown, Jeremy Brown, Jeremy Brown, Martin M. Brown, Martin M. Brown, Victoria Tzortziou Brown, Traolach Brugha, Nigel J. Brunskill, Maya H Buch, Philip Buckley, Anda Bularga, Edward T. Bullmore, L. Burden, Teresa Burdett, D Burn, Graham Burns, Angus C. Burns, John Busby, R. Butcher, Adeel A. Butt, Suzanne Byrne, Paula Cairns, Philip C. Calder, E Calvelo, H Carborn, Brittany Card, Christine Carr, L. Carr, Gail Carson, P Carter, Anna Casey, Mark Philip Cassar, Jorunn Pauline Cavanagh, Manish Chablani, R C Chambers, Francis K.L. Chan, K.M. Channon, K Chapman, A Charalambou, Nazia Chaudhuri, Anna M. Checkley, J Chen, Yu Cheng, L Chetham, C Childs, Edwin R. Chilvers, Hector Chinoy, Amedeo Chiribiri, K Chong-James, Noura J. Choudhury, Phil Chowienczyk, C D C Christie, M Chrystal, Diane Clark, Collin M. Clark, Jennifer Clarke, Sara Clohisey, G Coakley, Z Coburn, S Coetzee, Joby Cole, Christopher M. Coleman, F Conneh, David Connell, Bronwen Connolly, L Connor, A Cook, Brendan Cooper, D. James Cooper, Sheldon C. Cooper, Debra Copeland, Tracey Cosier, M Coulding, C Coupland, Eline G. M. Cox, Tom Craig, Philippe Crisp, D Cristiano, Michael G. Crooks, Adam Cross, I Cruz, Paul Cullinan, Daniel J. Cuthbertson, Luke Daines, M Dalton, Patricia Daly, A Daniels, Paul Dark, J Dasgin, Abel P. David, C David, Elin Haf Davies, Ffyon Davies, Gwyneth A. Davies, Gwyneth A. Davies, Katherine Davies, Jennifer Dawson, E Daynes, B Deakin, Andrew Deans, C Deas, J Deery, Sylviane Defres, Amanda Dell, K Dempsey, Emma Denneny, John Dennis, Amy Dewar, R Dharmagunawardena, Chris Dickens, A Dipper, Sarah Diver, S N Diwanji, Michael J. Dixon, Ratko Djukanović, Hannah Dobson, Susan L. Dobson, A Donaldson, Tim Dong, Natalie Dormand, Andrew Dougherty, Rowan Dowling, S Drain, K Draxlbauer, K. Drury, P Dulawan, A Dunleavy, S Dunn, J Earley, Sarah Edwards, Charlotte L. Edwardson, H El-Taweel, Angela Elliott, Katharine Elliott, Y Ellis, A Elmer, D Evans, Helen Evans, Jonathan Evans, Rachael A Evans, Rhodri Evans, Teriann Evans, C Evenden, Lynsey Evison, Laura Fabbri, Sara Fairbairn, Andrea D. Fairman, K Fallon, David Faluyi, C Favager, T Fayzan, J. Featherstone, Tim Felton, J Finch, Simon J. Finney, J Finnigan, Lucy Finnigan, Helen L. Fisher, Simon Fletcher, R Flockton, M. G. Flynn, H Foot, David Foote, James D. Ford, Daniel Forton, E Fraile, C Francis, Rebecca Francis, Sarah Francis, Adam Frankel, Emily Fraser, Robert C. Free, Nigel French, Xiaotong Fu, James Furniss, L. Garner, Nandan Gautam, J George, P M George, Michael Gibbons, Michael Gill, L Gilmour, Fergus Gleeson, J Glossop, S. W. Glover, Nigel Goodman, C Goodwin, Bibek Gooptu, Howard S. Gordon, T Gorsuch, M Greatorex, Paul L. Greenhaff, A Greenhalgh, John P. Greenwood, H Gregory, R. Gregory, D Grieve, Denise Griffin, Lori Griffiths, A-M Guerdette, B Guillen Guio, Mahitha Gummadi, Ayush Gupta, Sambasivarao Gurram, Elspeth Guthrie, Z Guy, H Henson, Kate Hadley, A Haggar, Kirsten Hainey, Brigid Hairsine, Pranabashis Haldar, Isabella Hall, L Hall, Mark Halling‐Brown, R Hamil, A Hancock, Kerry Hancock, Neil A. Hanley, Sulaimaan Haq, Hayley Hardwick, Elaine Hardy, T Hardy, Beverley Hargadon, Kevin J. Harrington, Emma Harris, Phillippa Harrison, A Harvey, M Harvey, M Harvie, Lynn Haslam‐Larmer, May Havinden-Williams, Jason E. Hawkes, N Hawkings, J Haworth, A Hayday, M Haynes, Jon Hazeldine, T Hazelton, Cheryl Heeley, Jonathan L. Heeney, Melissa Heightman, Morag Henderson, L Hesselden, Melissa Hewitt, V Highett, Toby Hillman, T Hiwot, A Hoare, M Hoare, J Hockridge, P Hogarth, A Holbourn, Sara Holden, Luke Holdsworth, D Holgate, M Holland, L Holloway, K. Holmes, Manisha Holmes, B Holroyd-Hind, L Holt, Anil Hormis, Akram A. Hosseini, Matthew Hotopf, Kirsten Howard, Alice Howell, E Hufton, Alun D. Hughes, Joel W. Hughes, R Hughes, A Humphries, Nathan T. M. Huneke, E Hurditch, Masud Husain, Tracy Hussell, J Hutchinson, Wadah Ibrahim, F Ilyas, J Ingham, L Ingram, D Ionita, K Isaacs, Khalida Ismail, Thomas Jackson, W Y James, C Jarman, Ian Jarrold, Hannah Jarvis, R Jastrub, B Jayaraman, Peter Jezzard, K Jiwa, Candace Johnson, Steven Johnson, D Johnston, Caroline J. Jolley, D Jones, Graeme Jones, H. Jones, H. Jones, Ian A. Jones, L Jones, S Jones, S Jose, T Kabir, Georgios Kaltsakas, Vicky Kamwa, N. Kanellakis, S Kaprowska, Zunaira Kausar, Natalie Keenan, Sadie Kelly, Graham J. Kemp, Helen Kerslake, A L Key, Fasihul Khan, Kamlesh Khunti, Susan Kilroy, B. King, C King, L. Kingham, Jodie Kirk, Pádraig T. Kitterick, Paul Klenerman, Lucy Knibbs, Susan Knight, A. Knighton, Onn Min Kon, Samantha S.C. Kon, Samantha S.C. Kon, S. Koprowska, Ania Korszun, Ivan Koychev, C Kurasz, P Kurupati, Charles Laing, H. Lamlum, G Landers, Claudia Langenberg, Daniel Lasserson, Lara Lavelle-Langham, Alison M. Lawrie, Claire Lawson, Claire Lawson, A Layton, A Lea, D Lee, J-H Lee, E Lee, K. Leitch, R Lenagh, Daniel J. Lewis, J. R. Lewis, Virginia Lewis, N Lewis-Burke, X Li, Teresa Light, Liz Lightstone, W. Lilaonitkul, L. Lim, S Linford, Anne Lingford‐Hughes, Marc Lipman, Kamal Liyanage, Adam Lloyd, Sarah Logan, David A. Lomas, Ronda Loosley, Harpreet Lota, Wayne Lovegrove, Alice Lucey, Elena Lukaschuk, A Lye, C. Lynch, Steven MacDonald, Guy MacGowan, Irene Macharia, J Mackie, L Macliver, S Madathil, G Madzamba, N Magee, M M Magtoto, N Mairs, Nauman Majeed, Eugene O. Major, Flora Malein, Michael H. Malim, Georgia Mallison, Sema Mandal, Kenneth Mangion, Charlotte Manisty, R Manley, Keith L. March, Stefan J. Marciniak, Pietro Marino, M Mariveles, E Marouzet, S. Marsh, Ben G. Marshall, Michael S. Marshall, James Martín, Adrian R. Martineau, Leonardo Martín Vásquez Martínez, Nick Maskell, Darwin Matila, Wadzanai Matimba-Mupaya, Lauren Matthews, A Mbuyisa, Stephen P. McAdoo, J Weir McCall, R. Hamish McAllister‐Williams, Angela McArdle, P McArdle, D McAulay, Jacqueline McCormick, W McCormick, P McCourt, Lorcan McGarvey, Christopher McGee, Kirsty McGee, J McGinness, K McGlynn, A McGovern, Heather McGuinness, Iain B. McInnes, J McIntosh, E McIvor, K McIvor, L McLeavey, Anne McMahon, Michael McMahon, Liam McMorrow, T Mcnally, Melitta A. McNarry, J McNeill, Alison McQueen, H McShane, C Mears, C Megson, S Megson, Puja Mehta, James Meiring, L Melling, Mark Mencias, Dan Menzies, Marta Merida Morillas, A Michael, Lea Milligan, Chris Miller, C Mills, Nicholas L. Mills, L Milner, S Misra, James Mitchell, A. Mohamed, N Mohamed, Sarhan Mohammed, Philip L. Molyneaux, W Monteiro, S Moriera, Anna Morley, Leigh Morrison, Richard Morriss, A Morrow, Alison Moss, Paul Moss, K Motohashi, N Msimanga, Elizabeta B. Mukaetova‐Ladinska, U Munawar, Jennifer Murira, Uttam Nanda, H Nassa, M Nasseri, A Neal, R. Needham, P Neill, Helen Newell, Tom Newman, A. Newton-Cox, Timothy R. Nicholson, D Nicoll, Claire M. Nolan, Maria Noonan, Chris Norman, Petr Novotný, J Nunag, Lorenza Nwafor, U Nwanguma, J Nyaboko, Kate O’Donnell, Conor O’Brien, L O'Brien, David O’Regan, N Odell, Graham S. Ogg, O Olaosebikan, C Oliver, Z Omar, L. Orriss-Dib, Lynn Osborne, R Osbourne, Marlies Ostermann, Christopher E. Overton, J. Owen, J Oxton, Jamie Pack, Edmund Pacpaco, Stella‐Maria Paddick, S Painter, Ashkan Pakzad, S. Palmer, Padmasayee Papineni, Kitty Paques, Kerry Paradowski, Manish Pareek, Helen Parfrey, Carmine M. Pariante, Sean Parker, Miles Parkes, J. Parmar, S Patale, B. Patel, Manish Patel, Suresh Patel, D Pattenadk, M Pavlides, Sarah Payne, Lyndsay Pearce, John E. Pearl, D. Peckham, Jessica Pendlebury, Yun Peng, Catherine Pennington, I Peralta, Emma Perkins, Zhane Peterkin, Tünde Pető, Nayia Petousi, Jennifer Petrie, J Phipps, J Pimm, Karen Piper Hanley, Riinu Pius, H Plant, Sven Plein, Tatiana Plekhanova, Megan Plowright, O Polgar, Lonneke van de Poll, Joanna C. Porter, S Portukhay, Neil Powell, A Prabhu, John Pratt, Angeline Price, Christopher Price, Christopher Price, D Price, L Price, L Price, A Prickett, J. Propescu, S. Pugmire, Sheena Quaid, J Quigley, H Qureshi, Ibraheem Qureshi, Kavita Radhakrishnan, Markus Ralser, A. Ramos, H. Ramos, J Rangeley, B Rangelov, L Ratcliffe, P Ravencroft, A Reddington, Raghunath Reddy, H Redfearn, Dawn Redwood, Anna Reed, Megan Rees, T Rees, Karen Regan, Will Reynolds, Cinthia Mucci Ribeiro, A Richards, E Richardson, Pilar Rivera‐Ortega, K. Roberts, Elaine Robertson, Emma C. Robinson, Lisa A. Robinson, L Roche, Chloe Roddis, J. Rodger, Amelia Ross, G Ross, J Rossdale, Anthony Rostron, Anna Rowe, A Rowland, J Rowland, Krishna Chandra Roy, Maxim Roy, Igor Rudan, R Russell, Emma Russell, G Saalmink, R. Sabit, Elizabeth K. Sage, T Samakomva, N Samani, Claire Sampson, Katie Samuel, R Samuel, Amanda Sanderson, Elizabeth Sapey, Dinesh Saralaya, J. Sargant, C Sarginson, Thea Sass, Naveed Sattar, Karen Saunders, Peter Saunders, Laura Saunders, Heather Savill, W Saxon, Avan Aihie Sayer, J Schronce, Wilhelm Schwaeble, K Scott, Nicholas M. Selby, T Sewell, Kanan Shah, Pallav L. Shah, Manu Shankar‐Hari, Manish Sharma, Claire C. Sharpe, Michael Sharpe, S Shashaa, Albert C. Shaw, Kaitlin Shaw, Victoria Shaw, Sarah Shelton, L Shenton, K Shevket, Jay M. Short, S Siddique, Salman Siddiqui, J Sidebottom, Louise Sigfrid, G Simons, Jennifer Simpson, Nicholas Simpson, Claire Singh, Sally Singh, D Sissons, J Skeemer, Katie Slack, Anne Smith, D Smith, Stephen M. Smith, John A. Smith, Lauren C. Smith, M Soares, T S Solano, Reanne Solly, A R Solstice, T Soulsby, David Southern, D. Sowter, Mark Spears, Lisa Spencer, F Speranza, Louise Stadon, Stefan Stanel, N Steele, Michael Steiner, David J. Stensel, G Stephens, L Stephenson, M Stern, Iain Stewart, R Stimpson, Skye Stockdale, James Stockley, William Thornley Stoker, Richard Stone, W Storrar, A. Storrie, Kim Storton, Jeffrey S. A. Stringer, Sophia Strong-Sheldrake, Natalie Stroud, Christian P Subbe, Cathie Sudlow, Z Suleiman, Charlotte Summers, Christina Summersgill, D Sutherland, Dominic L. Sykes, Robert Sykes, Nick P. Talbot, Ai Lyn Tan, L Tarusan, Vera Tavoukjian, Alex H. Taylor, C Taylor, J Taylor, A Te, H Tedd, CJ Tee, J Teixeira, Helen Tench, S. Terry, S. Thackray-Nocera, Favas Thaivalappil, B Thamu, David Thickett, C Thomas, S Thomas, Andrew Thomas, T Thomas-Woods, T Thompson, A. A. Roger Thompson, T Thornton, J Tilley, N Tinker, Gerlynn Tiongson, Martin D. Tobin, James Tomlinson, Catherine Tong, Rhian M. Touyz, K A Tripp, Elizabeth M. Tunnicliffe, Alison E. Turnbull, Emma L. Turner, Steve Turner, Victoria Turner, K. Turner, Sharon Turney, Lance Turtle, H. Turton, J Ugoji, R Ugwuoke, Rachel Upthegrove, Jonathan Valabhji, M. Ventura, Joanne Vere, Carinna Vickers, B Vinson, Erin A. Wade, Phillip Wade, Thomas W. Wainwright, L O Wajero, S Walder, S Walker, S Walker, Emma Wall, T Wallis, Sharon Walmsley, Jessica A. Walsh, S Walsh, L Warburton, Tom Ward, K Warwick, Helen Wassall, Sharon Waterson, Eleanor Watson, Lea C. Watson, Judith Watson, Carly Welch, H Welch, B Welsh, Simon Wessely, S West, H Weston, Helen Wheeler, Simon R. White, Victor Whitehead, Julie Whitney, Spence Whittaker, B. Whittam, V Whitworth, Andrew Wight, Jim M. Wild, M Wilkins, Dean Wilkinson, Nefyn Williams, Nefyn Williams, Justin Williams, S A Williams-Howard, Michelle Willicombe, Guillermo B. Willis, J Willoughby, A Wilson, David M. Wilson, Iseult Wilson, Nicola Window, Miles D. Witham, R Wolf-Roberts, C Wood, Felix Woodhead, Jeffrey A. Woods, Joanne Wormleighton, J Worsley, David C. Wraith, C Wrey Brown, Clinton B. Wright, L Wright, S Wright, J Wyles, Inez Wynter, Mengxin Xu, N Yasmin, S Yasmin, Thomas Yates, Kay Por Yip, Bob Young, Scott Young, Alison L. Young, Ahmed Yousuf, A. Zawia, Lisa Zeidan, Boya Zhao, O Zongo - The Lancet 2022 cited by 424

BACKGROUND: No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. FINDINGS: 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7-9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46-0·99]), obesity (0·50 [0·34-0·74]) and invasive mechanical ventilation (0·42 [0·23-0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74-1·00]), at 5 months (0·74 [0·64-0·88]) to 1 year (0·75 [0·62-0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. INTERPRETATION: The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. FUNDING: UK Research and Innovation and National Institute for Health Research.