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1. Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study – PHOSP-COVID

Author: Omer Elneima, John R. Hurst, Carlos Echevarria, Jennifer K. Quint, Samantha Walker, Salman Siddiqui, Petr Novotny, Paul E. Pfeffer, Jeremy S. Brown, Manu Shankar-Hari, Hamish J.C. McAuley, Olivia C. Leavy, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Matthew Richardson, Ruth M. Saunders, Victoria C. Harris, Linzy Houchen-Wolloff, Neil J. Greening, Ewen M. Harrison, Annemarie B. Docherty, Nazir I. Lone, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Rachael A. Evans, Louise V. Wain, Aziz Sheikh, Chris E. Brightling, Anthony De Soyza, Liam G. Heaney, J.K. Baillie, N.I. Lone, E. Pairo-Castineira, N. Avramidis, K. Rawlik, S Jones, L. Armstrong, B. Hairsine, H. Henson, C. Kurasz, A. Shaw, L. Shenton, H. Dobson, A. Dell, S. Fairbairn, N. Hawkings, J. Haworth, M. Hoare, V. Lewis, A. Lucey, G. Mallison, H. Nassa, C. Pennington, A. Price, C. Price, A. Storrie, G. Willis, S. Young, K. Poinasamy, S. Walker, I. Jarrold, A. Sanderson, K. Chong-James, C. David, W.Y. James, P. Pfeffer, O. Zongo, A. Martineau, C. Manisty, C. Armour, V. Brown, J. Busby, B. Connolly, T. Craig, S. Drain, L.G. Heaney, B. King, N. Magee, E. Major, D. McAulay, L. McGarvey, J. McGinness, T. Peto, R. Stone, A. Bolger, F. Davies, A. Haggar, J. Lewis, A. Lloyd, R. Manley, E. McIvor, D. Menzies, K. Roberts, W. Saxon, D. Southern, C. Subbe, V. Whitehead, A. Bularga, N.L. Mills, J. Dawson, H. El-Taweel, L. Robinson, L. Brear, K. Regan, D. Saralaya, K. Storton, S. Amoils, A. Bermperi, I. Cruz, K. Dempsey, A. Elmer, J. Fuld, H. Jones, S. Jose, S. Marciniak, M. Parkes, C. Ribeiro, J. Taylor, M. Toshner, L. Watson, J. Worsley, L. Broad, T. Evans, M. Haynes, L. Jones, L. Knibbs, A. McQueen, C. Oliver, K. Paradowski, R. Sabit, J. Williams, I. Jones, L. Milligan, E. Harris, C. Sampson, E. Davies, C. Evenden, A. Hancock, K. Hancock, C. Lynch, M. Rees, L. Roche, N. Stroud, T. Thomas-Woods, S. Heller, T. Chalder, K. Shah, E. Robertson, B. Young, M. Babores, M. Holland, N. Keenan, S. Shashaa, H. Wassall, L. Austin, E. Beranova, T. Cosier, J. Deery, T. Hazelton, H. Ramos, R. Solly, S. Turney, H. Weston, M. Ralser, L. Pearce, S. Pugmire, W. Stoker, A. Wilson, W. McCormick, E. Fraile, J. Ugoji, L. Aguilar Jimenez, G. Arbane, S. Betts, K. Bisnauthsing, A. Dewar, N. Hart, G. Kaltsakas, H. Kerslake, M.M. Magtoto, P. Marino, L.M. Martinez, M. Ostermann, J. Rossdale, T.S. Solano, M. Alvarez Corral, A. Arias, E. Bevan, D. Griffin, J. Martin, J. Owen, S. Payne, A. Prabhu, A. Reed, W. Storrar, N. Williams, C. Wrey Brown, T. Burdett, J. Featherstone, C. Lawson, A. Layton, C. Mills, L. Stephenson, Y. Ellis, P. Atkin, K. Brindle, M.G. Crooks, K. Drury, N. Easom, R. Flockton, L. Holdsworth, A. Richards, D.L. Sykes, S. Thackray-Nocera, C. Wright, S. Coetzee, K. Davies, R. Hughes, R. Loosley, H. McGuinness, A. Mohamed, L. O'Brien, Z. Omar, E. Perkins, J. Phipps, G. Ross, A. Taylor, H. Tench, R. Wolf-Roberts, L. Burden, E. Calvelo, B. Card, C. Carr, E.R. Chilvers, D. Copeland, P. Cullinan, P. Daly, L. Evison, T. Fayzan, H. Gordon, S. Haq, R.G. Jenkins, C. King, O. Kon, K. March, M. Mariveles, L. McLeavey, N. Mohamed, S. Moriera, U. Munawar, J. Nunag, U. Nwanguma, L. Orriss-Dib, A. Ross, M. Roy, E. Russell, K. Samuel, J. Schronce, N. Simpson, L. Tarusan, D.C. Thomas, C. Wood, N. Yasmin, D. Altmann, L.S. Howard, D. Johnston, A. Lingford-Hughes, W.D-C. Man, J. Mitchell, P.L. Molyneaux, C. Nicolaou, D.P. O'Regan, L. Price, J. Quint, D. Smith, R.S. Thwaites, J. Valabhji, S. Walsh, C.M. Efstathiou, F. Liew, A. Frankel, L. Lightstone, S. McAdoo, M. Wilkins, M. Willicombe, R. Touyz, A-M. Guerdette, M. Hewitt, R. Reddy, K. Warwick, S. White, A. McMahon, M. Malim, K. Bramham, M. Brown, K. Ismail, T. Nicholson, C. Pariante, C. Sharpe, S. Wessely, J. Whitney, O. Adeyemi, R. Adrego, H. Assefa-Kebede, J. Breeze, S. Byrne, P. Dulawan, A. Hoare, C.J. Jolley, A. Knighton, S. Patale, I. Peralta, N. Powell, A. Ramos, K. Shevket, F. Speranza, A. Te, A. Shah, A. Chiribiri, C. O'Brien, A. Hayday, A. Ashworth, P. Beirne, J. Clarke, C. Coupland, M. Dalton, C. Favager, J. Glossop, J. Greenwood, L. Hall, T. Hardy, A. Humphries, J. Murira, D. Peckham, S. Plein, J. Rangeley, G. Saalmink, A.L. Tan, E. Wade, B. Whittam, N. Window, J. Woods, G. Coakley, L. Turtle, L. Allerton, A.M. Allt, M. Beadsworth, A. Berridge, J. Brown, S. Cooper, A. Cross, S. Defres, S.L. Dobson, J. Earley, N. French, W. Greenhalf, K. Hainey, H.E. Hardwick, J. Hawkes, V. Highett, S. Kaprowska, A.L. Key, L. Lavelle-Langham, N. Lewis-Burke, G. Madzamba, F. Malein, S. Marsh, C. Mears, L. Melling, M.J. Noonan, L. Poll, J. Pratt, E. Richardson, A. Rowe, M.G. Semple, V. Shaw, K.A. Tripp, L.O. Wajero, S.A. Williams-Howard, D.G. Wootton, J. Wyles, S.N. Diwanji, S. Gurram, P. Papineni, S. Quaid, G.F. Tiongson, E. Watson, A. Briggs, M. Marks, C. Hastie, N. Rogers, N. Smith, D. Stensel, L. Bishop, K. McIvor, P. Rivera-Ortega, B. Al-Sheklly, C. Avram, J. Blaikely, M. Buch, N. Choudhury, D. Faluyi, T. Felton, T. Gorsuch, N.A. Hanley, A. Horsley, T. Hussell, Z. Kausar, N. Odell, R. Osbourne, K. Piper Hanley, K. Radhakrishnan, S. Stockdale, T. Kabir, J.T. Scott, P.J.M. Openshaw, I.D. Stewart, D. Burn, A. Ayoub, G. Burns, G. Davies, A. De Soyza, C. Echevarria, H. Fisher, C. Francis, A. Greenhalgh, P. Hogarth, J. Hughes, K. Jiwa, G. Jones, G. MacGowan, D. Price, A. Sayer, J. Simpson, H. Tedd, S. Thomas, S. West, M. Witham, S. Wright, A. Young, M.J. McMahon, P. Neill, D. Anderson, N. Basu, H. Bayes, A. Brown, A. Dougherty, K. Fallon, L. Gilmour, D. Grieve, K. Mangion, A. Morrow, R. Sykes, C. Berry, I.B. McInnes, K. Scott, F. Barrett, A. Donaldson, E.K. Sage, D. Bell, R. Hamil, K. Leitch, L. Macliver, M. Patel, J. Quigley, A. Smith, B. Welsh, G. Choudhury, S. Clohisey, A. Deans, A.B. Docherty, J. Furniss, E.M. Harrison, S. Kelly, A. Sheikh, J.D. Chalmers, D. Connell, C. Deas, A. Elliott, J. George, S. Mohammed, J. Rowland, A.R. Solstice, D. Sutherland, C.J. Tee, J. Bunker, R. Gill, R. Nathu, K. Holmes, H. Adamali, D. Arnold, S. Barratt, A. Dipper, S. Dunn, N. Maskell, A. Morley, L. Morrison, L. Stadon, S. Waterson, H. Welch, B. Jayaraman, T. Light, I. Vogiatzis, P. Almeida, C.E. Bolton, A. Hosseini, L. Matthews, R. Needham, K. Shaw, A.K. Thomas, J. Bonnington, M. Chrystal, C. Dupont, P.L. Greenhaff, A. Gupta, W. Jang, S. Linford, A. Nikolaidis, S. Prosper, A. Burns, N. Kanellakis, V.M. Ferreira, C. Nikolaidou, C. Xie, M. Ainsworth, A. Alamoudi, A. Bloss, P. Carter, M. Cassar, J. Chen, F. Conneh, T. Dong, R.I. Evans, E. Fraser, J.R. Geddes, F. Gleeson, P. Harrison, M. Havinden-Williams, L.P. Ho, P. Jezzard, I. Koychev, P. Kurupati, H. McShane, C. Megson, S. Neubauer, D. Nicoll, G. Ogg, E. Pacpaco, M. Pavlides, Y. Peng, N. Petousi, J. Pimm, N.M. Rahman, B. Raman, M.J. Rowland, K. Saunders, M. Sharpe, N. Talbot, E.M. Tunnicliffe, A. Korszun, S. Kerr, R.E. Barker, D. Cristiano, N. Dormand, P. George, M. Gummadi, S. Kon, K. Liyanage, C.M. Nolan, B. Patel, S. Patel, O. Polgar, P. Shah, S. Singh, J.A. Walsh, M. Gibbons, S. Ahmad, S. Brill, J. Hurst, H. Jarvis, L. Lim, S. Mandal, D. Matila, O. Olaosebikan, C. Singh, C. Laing, H. Baxendale, L. Garner, C. Johnson, J. Mackie, A. Michael, J. Newman, J. Pack, K. Paques, H. Parfrey, J. Parmar, A. Reddy, M. Halling-Brown, P. Dark, N. Diar-Bakerly, D. Evans, E. Hardy, A. Harvey, D. Holgate, S. Knight, N. Mairs, N. Majeed, L. McMorrow, J. Oxton, J. Pendlebury, C. Summersgill, R. Ugwuoke, S. Whittaker, W. Matimba-Mupaya, S. Strong-Sheldrake, P. Chowienczyk, J. Bagshaw, M. Begum, K. Birchall, R. Butcher, H. Carborn, F. Chan, K. Chapman, Y. Cheng, L. Chetham, C. Clark, Z. Coburn, J. Cole, M. Dixon, A. Fairman, J. Finnigan, H. Foot, D. Foote, A. Ford, R. Gregory, K. Harrington, L. Haslam, L. Hesselden, J. Hockridge, A. Holbourn, B. Holroyd-Hind, L. Holt, A. Howell, E. Hurditch, F. Ilyas, C. Jarman, A. Lawrie, J-H. Lee, E. Lee, R. Lenagh, A. Lye, I. Macharia, M. Marshall, A. Mbuyisa, J. McNeill, S. Megson, J. Meiring, L. Milner, S. Misra, H. Newell, T. Newman, C. Norman, L. Nwafor, D. Pattenadk, M. Plowright, J. Porter, P. Ravencroft, C. Roddis, J. Rodger, S.L. Rowland-Jones, P. Saunders, J. Sidebottom, J. Smith, L. Smith, N. Steele, G. Stephens, R. Stimpson, B. Thamu, A.A.R. Thompson, N. Tinker, K. Turner, H. Turton, P. Wade, J. Watson, I. Wilson, A. Zawia, L. Allsop, K. Bennett, P. Buckley, M. Flynn, M. Gill, C. Goodwin, M. Greatorex, H. Gregory, C. Heeley, L. Holloway, M. Holmes, J. Hutchinson, J. Kirk, W. Lovegrove, T.A. Sewell, S. Shelton, D. Sissons, K. Slack, S. Smith, D. Sowter, S. Turner, V. Whitworth, I. Wynter, J. Tomlinson, L. Warburton, S. Painter, S. Palmer, D. Redwood, J. Tilley, C. Vickers, T. Wainwright, G. Breen, M. Hotopf, R. Aul, D. Forton, M. Ali, A. Dunleavy, M. Mencias, N. Msimanga, T. Samakomva, S. Siddique, V. Tavoukjian, J. Teixeira, R. Ahmed, R. Francis, L. Connor, A. Cook, G.A. Davies, T. Rees, F. Thaivalappil, C. Thomas, M. McNarry, K.E. Lewis, M. Coulding, S. Kilroy, J. McCormick, J. McIntosh, V. Turner, J. Vere, A. Butt, H. Savill, S.S. Kon, G. Landers, H. Lota, S. Portukhay, M. Nasseri, A. Daniels, A. Hormis, J. Ingham, L. Zeidan, M. Chablani, L. Osborne, S. Aslani, A. Banerjee, R. Batterham, G. Baxter, R. Bell, A. David, E. Denneny, A.D. Hughes, W. Lilaonitkul, P. Mehta, A. Pakzad, B. Rangelov, B. Williams, J. Willoughby, M. Xu, N. Ahwireng, D. Bang, D. Basire, J.S. Brown, R.C. Chambers, A. Checkley, R. Evans, M. Heightman, T. Hillman, J. Jacob, R. Jastrub, M. Lipman, S. Logan, D. Lomas, M. Merida Morillas, H. Plant, J.C. Porter, K. Roy, E. Wall, T. Treibel, N. Ahmad Haider, C. Atkin, R. Baggott, M. Bates, A. Botkai, A. Casey, B. Cooper, J. Dasgin, C. Dawson, K. Draxlbauer, N. Gautam, J. Hazeldine, T. Hiwot, S. Holden, K. Isaacs, T. Jackson, V. Kamwa, D. Lewis, J.M. Lord, S. Madathil, C. McGhee, K. McGee, A. Neal, A. Newton-Cox, J. Nyaboko, D. Parekh, Z. Peterkin, H. Qureshi, L. Ratcliffe, E. Sapey, J. Short, T. Soulsby, J. Stockley, Z. Suleiman, T. Thompson, M. Ventura, S. Walder, C. Welch, D. Wilson, S. Yasmin, K.P. Yip, N. Chaudhuri, C. Childs, R. Djukanovic, S. Fletcher, M. Harvey, M.G. Jones, E. Marouzet, B. Marshall, R. Samuel, T. Sass, T. Wallis, H. Wheeler, R. Steeds, P. Beckett, C. Dickens, U. Nanda, M. Aljaroof, N. Armstrong, H. Arnold, H. Aung, M. Bakali, M. Bakau, E. Baldry, M. Baldwin, C. Bourne, M. Bourne, C.E. Brightling, N. Brunskill, P. Cairns, L. Carr, A. Charalambou, C. Christie, M.J. Davies, E. Daynes, S. Diver, R. Dowling, S. Edwards, C. Edwardson, O. Elneima, H. Evans, R.A. Evans, J. Finch, S. Finney, S. Glover, N. Goodman, B. Gooptu, N.J. Greening, K. Hadley, P. Haldar, B. Hargadon, V.C. Harris, L. Houchen-Wolloff, W. Ibrahim, L. Ingram, K. Khunti, A. Lea, D. Lee, H.J.C. McAuley, G.P. McCann, P. McCourt, T. McNally, G. Mills, W. Monteiro, M. Pareek, S. Parker, A. Prickett, I.N. Qureshi, A. Rowland, R. Russell, M. Sereno, A. Shikotra, S. Siddiqui, A. Singapuri, S.J. Singh, J. Skeemer, M. Soares, E. Stringer, S. Terry, T. Thornton, M. Tobin, T.J.C. Ward, F. Woodhead, T. Yates, A.J. Yousuf, B. Guillen Guiio, O.C. Leavy, L.V. Wain, M. Broome, P. McArdle, D. Thickett, R. Upthegrove, D. Wilkinson, P. Moss, D. Wraith, J. Evans, E. Bullmore, J.L. Heeney, C. Langenberg, W. Schwaeble, C. Summers, J. Weir McCall, D. Adeloye, D.E. Newby, R. Pius, I. Rudan, M. Shankar-Hari, C.L. Sudlow, M. Thorpe, S. Walmsley, B. Zheng, L. Allan, C. Ballard, A. McGovern, J. Dennis, J. Cavanagh, S. MacDonald, K. O'Donnell, J. Petrie, N. Sattar, M. Spears, E. Guthrie, M. Henderson, R.J. Allen, M. Bingham, T. Brugha, R. Free, D. Jones, L. Gardiner, A.J. Moss, E. Mukaetova-Ladinska, P. Novotny, C. Overton, J.E. Pearl, T. Plekhanova, M. Richardson, N. Samani, J. Sargent, M. Sharma, M. Steiner, C. Taylor, C. Tong, E. Turner, J. Wormleighton, B. Zhao, K. Ntotsis, R.M. Saunders, D. Lozano-Rojas, D. Cuthbertson, G. Kemp, A. McArdle, B. Michael, W. Reynolds, L.G. Spencer, B. Vinson, M. Ashworth, K. Abel, H. Chinoy, B. Deakin, M. Harvie, C.A. Miller, S. Stanel, P. Barran, D. Trivedi, H. McAllister-Williams, S. Paddick, A. Rostron, J.P. Taylor, D. Baguley, C. Coleman, E. Cox, L. Fabbri, S. Francis, I. Hall, E. Hufton, S. Johnson, F. Khan, P. Kitterick, R. Morriss, N. Selby, L. Wright, C. Antoniades, A. Bates, M. Beggs, K. Bhui, K. Breeze, K.M. Channon, D. Clark, X. Fu, M. Husain, X. Li, E. Lukaschuk, C. McCracken, K. McGlynn, R. Menke, K. Motohashi, T.E. Nichols, G. Ogbole, S. Piechnik, I. Propescu, J. Propescu, A.A. Samat, Z.B. Sanders, L. Sigfrid, M. Webster, L. Kingham, P. Klenerman, H. Lamlum, G. Carson, M. Taquet, L. Finnigan, L.C. Saunders, J.M. Wild, P.C. Calder, N. Huneke, G. Simons, D. Baldwin, S. Bain, L. Daines, E. Bright, P. Crisp, R. Dharmagunawardena, M. Stern, L. Bailey, A. Reddington, A. Wight, A. Ashish, J. Cooper, E. Robinson, A. Broadley, L. Barman, C. Brookes, K. Elliott, L. Griffiths, Z. Guy, K. Howard, D. Ionita, H. Redfearn, C. Sarginson, and A. Turnbull
Subjects: Medicine
Abstract: Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p
Published: 2024
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2. Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort studyResearch in context

Author: Hamish J.C. McAuley, Rachael A. Evans, Charlotte E. Bolton, Christopher E. Brightling, James D. Chalmers, Annemarie B. Docherty, Omer Elneima, Paul L. Greenhaff, Ayushman Gupta, Victoria C. Harris, Ewen M. Harrison, Ling-Pei Ho, Alex Horsley, Linzy Houchen-Wolloff, Caroline J. Jolley, Olivia C. Leavy, Nazir I. Lone, William D-C Man, Michael Marks, Dhruv Parekh, Krisnah Poinasamy, Jennifer K. Quint, Betty Raman, Matthew Richardson, Ruth M. Saunders, Marco Sereno, Aarti Shikotra, Amisha Singapuri, Sally J. Singh, Michael Steiner, Ai Lyn Tan, Louise V. Wain, Carly Welch, Julie Whitney, Miles D. Witham, Janet Lord, Neil J. Greening, K. Abel, H. Adamali, D. Adeloye, O. Adeyemi, R. Adrego, L.A. Aguilar Jimenez, S. Ahmad, N. Ahmad Haider, R. Ahmed, N. Ahwireng, M. Ainsworth, B. Al-Sheklly, A. Alamoudi, M. Ali, M. Aljaroof, A.M. All, L. Allan, R.J. Allen, L. Allerton, L. Allsop, P. Almeida, D. Altmann, M. Alvarez Corral, S. Amoils, D. Anderson, C. Antoniades, G. Arbane, A. Arias, C. Armour, L. Armstrong, N. Armstrong, D. Arnold, H. Arnold, A. Ashish, A. Ashworth, M. Ashworth, S. Aslani, H. Assefa-Kebede, C. Atkin, P. Atkin, R. Aul, H. Aung, L. Austin, C. Avram, A. Ayoub, M. Babores, R. Baggott, J. Bagshaw, D. Baguley, L. Bailey, J.K. Baillie, S. Bain, M. Bakali, M. Bakau, E. Baldry, D. Baldwin, M. Baldwin, C. Ballard, A. Banerjee, B. Bang, R.E. Barker, L. Barman, S. Barratt, F. Barrett, D. Basire, N. Basu, M. Bates, A. Bates, R. Batterham, H. Baxendale, H. Bayes, M. Beadsworth, P. Beckett, M. Beggs, M. Begum, P. Beirne, D. Bell, R. Bell, K. Bennett, E. Beranova, A. Bermperi, A. Berridge, C. Berry, S. Betts, E. Bevan, K. Bhui, M. Bingham, K. Birchall, L. Bishop, K. Bisnauthsing, J. Blaikely, A. Bloss, A. Bolger, C.E. Bolton, J. Bonnington, A. Botkai, C. Bourne, M. Bourne, K. Bramham, L. Brear, G. Breen, J. Breeze, A. Briggs, E. Bright, C.E. Brightling, S. Brill, K. Brindle, L. Broad, A. Broadley, C. Brookes, M. Broome, A. Brown, J. Brown, J.S. Brown, M. Brown, V. Brown, T. Brugha, N. Brunskill, M. Buch, P. Buckley, A. Bularga, E. Bullmore, L. Burden, T. Burdett, D. Burn, G. Burns, A. Burns, J. Busby, R. Butcher, A. Butt, S. Byrne, P. Cairns, P.C. Calder, E. Calvelo, H. Carborn, B. Card, C. Carr, L. Carr, G. Carson, P. Carter, A. Casey, M. Cassar, J. Cavanagh, M. Chablani, T. Chalder, J.D. Chalmers, R.C. Chambers, F. Chan, K.M. Channon, K. Chapman, A. Charalambou, N. Chaudhuri, A. Checkley, J. Chen, Y. Cheng, L. Chetham, C. Childs, E.R. Chilvers, H. Chinoy, A. Chiribiri, K. Chong-James, G. Choudhury, N. Choudhury, P. Chowienczyk, C. Christie, M. Chrystal, D. Clark, C. Clark, J. Clarke, S. Clohisey, G. Coakley, Z. Coburn, S. Coetzee, J. Cole, C. Coleman, F. Conneh, D. Connell, B. Connolly, L. Connor, A. Cook, B. Cooper, J. Cooper, S. Cooper, D. Copeland, T. Cosier, M. Coulding, C. Coupland, E. Cox, T. Craig, P. Crisp, D. Cristiano, M.G. Crooks, A. Cross, I. Cruz, P. Cullinan, D. Cuthbertson, L. Daines, M. Dalton, P. Daly, A. Daniels, P. Dark, J. Dasgin, A. David, C. David, E. Davies, F. Davies, G. Davies, G.A. Davies, K. Davies, M.J. Davies, J. Dawson, E. Daynes, A. De Soyza, B. Deakin, A. Deans, C. Deas, J. Deery, S. Defres, A. Dell, K. Dempsey, E. Denneny, J. Dennis, A. Dewar, R. Dharmagunawardena, N. Diar-Bakerly, C. Dickens, A. Dipper, S. Diver, S.N. Diwanji, M. Dixon, R. Djukanovic, H. Dobson, S.L. Dobson, A.B. Docherty, A. Donaldson, T. Dong, N. Dormand, A. Dougherty, R. Dowling, S. Drain, K. Draxlbauer, K. Drury, H.J.C. Drury, P. Dulawan, A. Dunleavy, S. Dunn, C. Dupont, J. Earley, N. Easom, C. Echevarria, S. Edwards, C. Edwardson, H. El-Taweel, A. Elliott, K. Elliott, Y. Ellis, A. Elmer, O. Elneima, D. Evans, H. Evans, J. Evans, R. Evans, R.A. Evans, R.I. Evans, T. Evans, C. Evenden, L. Evison, L. Fabbri, S. Fairbairn, A. Fairman, K. Fallon, D. Faluyi, C. Favager, T. Fayzan, J. Featherstone, T. Felton, J. Finch, S. Finney, J. Finnigan, L. Finnigan, H. Fisher, S. Fletcher, R. Flockton, M. Flynn, H. Foot, D. Foote, A. Ford, D. Forton, E. Fraile, C. Francis, R. Francis, S. Francis, A. Frankel, E. Fraser, R. Free, N. French, X. Fu, J. Fuld, J. Furniss, L. Garner, N. Gautam, J.R. Geddes, J. George, P. George, M. Gibbons, M. Gill, L. Gilmour, F. Gleeson, J. Glossop, S. Glover, N. Goodman, C. Goodwin, B. Gooptu, H. Gordon, T. Gorsuch, M. Greatorex, P.L. Greenhaff, W. Greenhalf, A. Greenhalgh, N.J. Greening, J. Greenwood, H. Gregory, R. Gregory, D. Grieve, D. Griffin, L. Griffiths, A.-M. Guerdette, B. Guillen Guio, M. Gummadi, A. Gupta, S. Gurram, E. Guthrie, Z. Guy, H.H. Henson, K. Hadley, A. Haggar, K. Hainey, B. Hairsine, P. Haldar, I. Hall, L. Hall, M. Halling-Brown, R. Hamil, A. Hancock, K. Hancock, N.A. Hanley, S. Haq, H.E. Hardwick, E. Hardy, T. Hardy, B. Hargadon, K. Harrington, E. Harris, V.C. Harris, E.M. Harrison, P. Harrison, N. Hart, A. Harvey, M. Harvey, M. Harvie, L. Haslam, M. Havinden-Williams, J. Hawkes, N. Hawkings, J. Haworth, A. Hayday, M. Haynes, J. Hazeldine, T. Hazelton, L.G. Heaney, C. Heeley, J.L. Heeney, M. Heightman, S. Heller, M. Henderson, L. Hesselden, M. Hewitt, V. Highett, T. Hillman, T. Hiwot, L.P. Ho, A. Hoare, M. Hoare, J. Hockridge, P. Hogarth, A. Holbourn, S. Holden, L. Holdsworth, D. Holgate, M. Holland, L. Holloway, K. Holmes, M. Holmes, B. Holroyd-Hind, L. Holt, A. Hormis, A. Horsley, A. Hosseini, M. Hotopf, L. Houchen-Wolloff, K. Howard, L.S. Howard, A. Howell, E. Hufton, A.D. Hughes, J. Hughes, R. Hughes, A. Humphries, N. Huneke, E. Hurditch, J. Hurst, M. Husain, T. Hussell, J. Hutchinson, W. Ibrahim, F. Ilyas, J. Ingham, L. Ingram, D. Ionita, K. Isaacs, K. Ismail, T. Jackson, J. Jacob, W.Y. James, W. Jang, C. Jarman, I. Jarrold, H. Jarvis, R. Jastrub, B. Jayaraman, R.G. Jenkins, P. Jezzard, K. Jiwa, C. Johnson, S. Johnson, D. Johnston, C.J. Jolley, D. Jones, G. Jones, H. Jones, I. Jones, L. Jones, M.G. Jones, S. Jones, S. Jose, T. Kabir, G. Kaltsakas, V. Kamwa, N. Kanellakis, S. Kaprowska, Z. Kausar, N. Keenan, S. Kelly, G. Kemp, S. Kerr, H. Kerslake, A.L. Key, F. Khan, K. Khunti, S. Kilroy, B. King, C. King, L. Kingham, J. Kirk, P. Kitterick, P. Klenerman, L. Knibbs, S. Knight, A. Knighton, O. Kon, S. Kon, S.S. Kon, S. Koprowska, A. Korszun, I. Koychev, C. Kurasz, P. Kurupati, C. Laing, H. Lamlum, G. Landers, C. Langenberg, D. Lasserson, L. Lavelle-Langham, A. Lawrie, C. Lawson, A. Layton, A. Lea, O.C. Leavy, D. Lee, J.-H. Lee, E. Lee, K. Leitch, R. Lenagh, D. Lewis, J. Lewis, K.E. Lewis, V. Lewis, N. Lewis-Burke, X. Li, T. Light, L. Lightstone, W. Lilaonitkul, L. Lim, S. Linford, A. Lingford-Hughes, M. Lipman, K. Liyanage, A. Lloyd, S. Logan, D. Lomas, N.I. Lone, R. Loosley, J.M. Lord, H. Lota, W. Lovegrove, A. Lucey, E. Lukaschuk, A. Lye, C. Lynch, S. MacDonald, G. MacGowan, I. Macharia, J. Mackie, L. Macliver, S. Madathil, G. Madzamba, N. Magee, M.M. Magtoto, N. Mairs, N. Majeed, E. Major, F. Malein, M. Malim, G. Mallison, W. D-C Man, S. Mandal, K. Mangion, C. Manisty, R. Manley, K. March, S. Marciniak, P. Marino, M. Mariveles, M. Marks, E. Marouzet, S. Marsh, B. Marshall, M. Marshall, J. Martin, A. Martineau, L.M. Martinez, N. Maskell, D. Matila, W. Matimba-Mupaya, L. Matthews, A. Mbuyisa, S. McAdoo, H. McAllister-Williams, A. McArdle, P. McArdle, D. McAulay, G.P. McCann, J. McCormick, W. McCormick, P. McCourt, L. McGarvey, C. McGee, K. Mcgee, J. McGinness, K. McGlynn, A. McGovern, H. McGuinness, I.B. McInnes, J. McIntosh, E. McIvor, K. McIvor, L. McLeavey, A. McMahon, M.J. McMahon, L. McMorrow, T. Mcnally, M. McNarry, J. McNeill, A. McQueen, H. McShane, C. Mears, C. Megson, S. Megson, P. Mehta, J. Meiring, L. Melling, M. Mencias, D. Menzies, M. Merida Morillas, A. Michael, C. Miller, L. Milligan, C. Mills, G. Mills, N.L. Mills, L. Milner, S. Misra, J. Mitchell, A. Mohamed, N. Mohamed, S. Mohammed, P.L. Molyneaux, W. Monteiro, S. Moriera, A. Morley, L. Morrison, R. Morriss, A. Morrow, A.J. Moss, P. Moss, K. Motohashi, N. Msimanga, E. Mukaetova-Ladinska, U. Munawar, J. Murira, U. Nanda, H. Nassa, M. Nasseri, A. Neal, R. Needham, P. Neill, S. Neubauer, D.E. Newby, H. Newell, T. Newman, J. Newman, A. Newton-Cox, T. Nicholson, D. Nicoll, A. Nikolaidis, C.M. Nolan, M.J. Noonan, C. Norman, P. Novotny, J. Nunag, L. Nwafor, U. Nwanguma, J. Nyaboko, C. O'Brien, K. O'Donnell, D. O'Regan, L. O’Brien, N. Odell, G. Ogg, O. Olaosebikan, C. Oliver, Z. Omar, P.J.M. Openshaw, L. Orriss-Dib, L. Osborne, R. Osbourne, M. Ostermann, C. Overton, J. Owen, J. Oxton, J. Pack, E. Pacpaco, S. Paddick, S. Painter, A. Pakzad, S. Palmer, P. Papineni, K. Paques, K. Paradowski, M. Pareek, D. Parekh, H. Parfrey, C. Pariante, S. Parker, M. Parkes, J. Parmar, S. Patale, B. Patel, M. Patel, S. Patel, D. Pattenadk, M. Pavlides, S. Payne, L. Pearce, J.E. Pearl, D. Peckham, J. Pendlebury, Y. Peng, C. Pennington, I. Peralta, E. Perkins, Z. Peterkin, T. Peto, N. Petousi, J. Petrie, P. Pfeffer, J. Phipps, J. Pimm, K. Piper Hanley, R. Pius, H. Plant, S. Plein, T. Plekhanova, M. Plowright, K. Poinasamy, O. Polgar, L. Poll, J.C. Porter, J. Porter, S. Portukhay, N. Powell, A. Prabhu, J. Pratt, A. Price, C. Price, D. Price, L. Price, A. Prickett, J. Propescu, S. Prosper, S. Pugmire, S. Quaid, J. Quigley, J. Quint, H. Qureshi, I.N. Qureshi, K. Radhakrishnan, N.M. Rahman, M. Ralser, B. Raman, A. Ramos, H. Ramos, J. Rangeley, B. Rangelov, L. Ratcliffe, P. Ravencroft, A. Reddington, R. Reddy, A. Reddy, H. Redfearn, D. Redwood, A. Reed, M. Rees, T. Rees, K. Regan, W. Reynolds, C. Ribeiro, A. Richards, E. Richardson, M. Richardson, P. Rivera-Ortega, K. Roberts, E. Robertson, E. Robinson, L. Robinson, L. Roche, C. Roddis, J. Rodger, A. Ross, G. Ross, J. Rossdale, A. Rostron, A. Rowe, A. Rowland, J. Rowland, M.J. Rowland, S.L. Rowland-Jones, K. Roy, M. Roy, I. Rudan, R. Russell, E. Russell, G. Saalmink, R. Sabit, E.K. Sage, T. Samakomva, N. Samani, C. Sampson, K. Samuel, R. Samuel, A. Sanderson, E. Sapey, D. Saralaya, J. Sargant, C. Sarginson, T. Sass, N. Sattar, K. Saunders, R.M. Saunders, P. Saunders, L.C. Saunders, H. Savill, W. Saxon, A. Sayer, J. Schronce, W. Schwaeble, J.T. Scott, K. Scott, N. Selby, M.G. Semple, M. Sereno, T.A. Sewell, A. Shah, K. Shah, P. Shah, M. Shankar-Hari, M. Sharma, C. Sharpe, M. Sharpe, S. Shashaa, A. Shaw, K. Shaw, V. Shaw, A. Sheikh, S. Shelton, L. Shenton, K. Shevket, A. Shikotra, J. Short, S. Siddique, S. Siddiqui, J. Sidebottom, L. Sigfrid, G. Simons, J. Simpson, N. Simpson, A. Singapuri, C. Singh, S. Singh, S.J. Singh, D. Sissons, J. Skeemer, K. Slack, A. Smith, D. Smith, S. Smith, J. Smith, L. Smith, M. Soares, T.S. Solano, R. Solly, A.R. Solstice, T. Soulsby, D. Southern, D. Sowter, M. Spears, L.G. Spencer, F. Speranza, L. Stadon, S. Stanel, N. Steele, M. Steiner, D. Stensel, G. Stephens, L. Stephenson, M. Stern, I. Stewart, R. Stimpson, S. Stockdale, J. Stockley, W. Stoker, R. Stone, W. Storrar, A. Storrie, K. Storton, E. Stringer, S. Strong-Sheldrake, N. Stroud, C. Subbe, C.L. Sudlow, Z. Suleiman, C. Summers, C. Summersgill, D. Sutherland, D.L. Sykes, R. Sykes, N. Talbot, A.L. Tan, L. Tarusan, V. Tavoukjian, A. Taylor, C. Taylor, J. Taylor, A. Te, H. Tedd, C.J. Tee, J. Teixeira, H. Tench, S. Terry, S. Thackray-Nocera, F. Thaivalappil, B. Thamu, D. Thickett, C. Thomas, D.C. Thomas, S. Thomas, A.K. Thomas, T. Thomas-Woods, T. Thompson, A.A.R. Thompson, T. Thornton, M. Thorpe, R.S. Thwaites, J. Tilley, N. Tinker, G.F. Tiongson, M. Tobin, J. Tomlinson, C. Tong, M. Toshner, R. Touyz, K.A. Tripp, E. Tunnicliffe, A. Turnbull, E. Turner, S. Turner, V. Turner, K. Turner, S. Turney, L. Turtle, H. Turton, J. Ugoji, R. Ugwuoke, R. Upthegrove, J. Valabhji, M. Ventura, J. Vere, C. Vickers, B. Vinson, E. Wade, P. Wade, L.V. Wain, T. Wainwright, L.O. Wajero, S. Walder, S. Walker, E. Wall, T. Wallis, S. Walmsley, J.A. Walsh, S. Walsh, L. Warburton, T.J.C. Ward, K. Warwick, H. Wassall, S. Waterson, E. Watson, L. Watson, J. Watson, J. Weir McCall, C. Welch, H. Welch, B. Welsh, S. Wessely, S. West, H. Weston, H. Wheeler, S. White, V. Whitehead, J. Whitney, S. Whittaker, B. Whittam, V. Whitworth, A. Wight, J. Wild, M. Wilkins, D. Wilkinson, B. Williams, N. Williams, J. Williams, S.A. Williams-Howard, M. Willicombe, G. Willis, J. Willoughby, A. Wilson, D. Wilson, I. Wilson, N. Window, M. Witham, R. Wolf-Roberts, C. Wood, F. Woodhead, J. Woods, D.G. Wootton, J. Wormleighton, J. Worsley, D. Wraith, C. Wrey Brown, C. Wright, L. Wright, S. Wright, J. Wyles, I. Wynter, M. Xu, N. Yasmin, S. Yasmin, T. Yates, K.P. Yip, B. Young, S. Young, A. Young, A.J. Yousuf, A. Zawia, L. Zeidan, B. Zhao, B. Zheng, and O. Zongo
Subjects: COVID-19, Physical frailty, Long-COVID, Fried's frailty phenotype, Hospitalisation, Medicine (General), R5-920
Abstract: Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.
Published: 2023
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3. Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy

Author: Yun-Fei Bai, Michelle Chiu, Elizabeth S. Chan, Peter Axerio-Cilies, Jie Lu, Linda Huh, Mary B. Connolly, Ilaria Guella, Matthew J. Farrer, Zhi-Qing David Xu, Lidong Liu, Michelle Demos, and Yu Tian Wang
Subjects: GABA a receptor, Epileptic encephalopathy, Mutation, Therapeutic options, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract We report the identification of a de novo GABRA1 (R214C) variant in a child with epileptic encephalopathy (EE), describe its functional characterization and pathophysiology, and evaluate its potential therapeutic options. The GABRA1 (R214C) variant was identified using whole exome sequencing, and the pathogenic effect of this mutation was investigated by comparing wild-type (WT) α1 and R214C α1 GABAA receptor-expressing HEK cells. GABA-evoked currents in these cells were recorded using whole-cell, outside-out macro-patch and cell-attached single-channel patch-clamp recordings. Changes to surface and total protein expression levels of WT α1 and R214C α1 were quantified using surface biotinylation assay and western blotting, respectively. Finally, potential therapeutic options were explored by determining the effects of modulators, including diazepam, insulin, and verapamil, on channel gating and receptor trafficking of WT and R214C GABAA receptors. We found that the GABRA1 (R214C) variant decreased whole-cell GABA-evoked currents by reducing single channel open time and both surface and total GABAA receptor expression levels. The GABA-evoked currents in R214C GABAA receptors could only be partially restored with benzodiazepine (diazepam) and insulin. However, verapamil treatment for 24 h fully restored the function of R214C mutant receptors, primarily by increasing channel open time. We conclude that the GABRA1 (R214C) variant reduces channel activity and surface expression of mutant receptors, thereby contributing to the pathogenesis of genetic EE. The functional restoration by verapamil suggests that it is a potentially new therapeutic option for patients with the R214C variant and highlights the value of precision medicine in the treatment of genetic EEs.
Published: 2019
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4. Rapid Quantum Magnetic IL-6 Point-of-Care Assay in Patients Hospitalized with COVID-19

Author: Johnny Atallah, Dakota Archambault, Jeffrey D. Randall, Adam Shepro, Lauren E. Styskal, David R. Glenn, Colin B. Connolly, Katelin Katsis, Kathleen Gallagher, Musie Ghebremichael, and Michael K. Mansour
Subjects: IL-6, COVID-19, diagnostics, ICU, mechanical ventilation, Luminex, Medicine (General), R5-920
Abstract: Interleukin-6 (IL-6) has been linked to several life-threatening disease processes. Developing a point-of-care testing platform for the immediate and accurate detection of IL-6 concentrations could present a valuable tool for improving clinical management in patients with IL-6-mediated diseases. Drawing on an available biobank of samples from 35 patients hospitalized with COVID-19, a novel quantum-magnetic sensing platform is used to determine plasma IL-6 concentrations. A strong correlation was observed between IL-6 levels measured by QDTI10x and the Luminex assay (r = 0.70, p-value < 0.001) and between QDTI80x and Luminex (r = 0.82, p-value < 0.001). To validate the non-inferiority of QDTI to Luminex in terms of the accuracy of IL-6 measurement, two clinical parameters—the need for intensive care unit admission and the need for mechanical intubation—were chosen. IL-6 concentrations measured by the two assays were compared with respect to these clinical outcomes. Results demonstrated a comparative predictive performance between the two assays with a significant correlation coefficient. Conclusion: In short, the QDTI assay holds promise for implementation as a potential tool for rapid clinical decision in patients with IL-6-mediated diseases. It could also reduce healthcare costs and enable the development of future various biomolecule point-of-care tests for different clinical scenarios.
Published: 2022
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5. Gene drive in species complexes: defining target organisms

Author: John B. Connolly, Jörg Romeis, Yann Devos, Debora C.M. Glandorf, Geoff Turner, and Mamadou B. Coulibaly
Subjects: GMO, population suppression, Anopheles, hybridisation, malaria, environmental risk assessment, Bioengineering, Biotechnology
Abstract: Engineered gene drives, which bias their own inheritance to increase in frequency in target populations, are being developed to control mosquito malaria vectors. Such mosquitoes can belong to complexes of both vector and nonvector species that can produce fertile interspecific hybrids, making vertical gene drive transfer (VGDT) to sibling species biologically plausible. While VGDT to other vectors could positively impact human health protection goals, VGDT to nonvectors might challenge biodiversity ones. Therefore, environmental risk assessment of gene drive use in species complexes invites more nuanced considerations of target organisms and nontarget organisms than for transgenes not intended to increase in frequency in target populations. Incorporating the concept of target species complexes offers more flexibility when assessing potential impacts from VGDT.
Published: 2023

6. Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo

Author: Ann Kristin Frøyset, Amanda J. Edson, Naouel Gharbi, Essa A. Khan, Daniel Dondorp, Qing Bai, Ettore Tiraboschi, Maximiliano L. Suster, Joanne B. Connolly, Edward A. Burton, and Kari E. Fladmark
Subjects: Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract: DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP+, a mitochondrial complex I inhibitor shown to induce dopaminergic cells death. In a global label-free proteomics analysis of wild type and transgenic larvae exposed to MPP+, 3418 proteins were identified, in which 366 proteins were differentially regulated. In particular, we identified enzymes belonging to primary metabolism to be among proteins affected by MPP+ in wild type animals, but not affected in the transgenic line. Moreover, by performing protein profiling on isolated astrocytes we showed that an increase in astrocytic DJ-1 expression up-regulated a large group of proteins associated with redox regulation, inflammation and mitochondrial respiration. The majority of these proteins have also been shown to be regulated by Nrf2. These findings provide a mechanistic insight into the protective role of astroglial up-regulation of DJ-1 and show that our transgenic zebrafish line with astrocytic DJ-1 over-expression can serve as a useful animal model to understand astrocyte-regulated neuroprotection associated with oxidative stress-related neurodegenerative disease. Keywords: DJ-1, Astrocyte, Parkinson's disease, Oxidative stress, Cell survival
Published: 2018
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7. Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development

Author: W. K. Tonui, V. Ahuja, C. J. Beech, J. B. Connolly, B. Dass, D. C. M. Glandorf, S. James, J. N. Muchiri, C. F. Mugoya, E. A. Okoree, H. Quemada, and J. Romeis
Subjects: Biological control, Genetic modification, Genetics, Animal Science and Zoology, Biosafety, Agronomy and Crop Science, Regulation, Risk assessment, Biotechnology
Abstract: Novel genetically modified biological control products (referred to as “GM biocontrol products”) are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products.
Published: 2022

8. Targeted Whole Exome Sequencing in Children With Early-Onset Epilepsy: Parent Experiences

Author: Armaghan Alam, Maksim Parfyonov, Camille Y. Huang, Inderpal Gill, Mary B. Connolly, and Judy Illes
Subjects: Parents, Epilepsy, Caregivers, Exome Sequencing, Pediatrics, Perinatology and Child Health, Humans, Genetic Testing, Neurology (clinical), Child
Abstract: This study investigated the experiences of 25 caregivers of children with early-onset, treatment-resistant epilepsy who pursued whole exome sequencing to determine the impact of the test results on their child’s treatment. Caregivers who consented to be recontacted were recruited from a previous study investigating the diagnostic yield of whole exome sequencing. A semistructured interview addressed questions based on one of 2 study phases. The first phase discussed the decision-making process for genetic testing (15 interviews), which revealed 4 major themes: (1) prognosis, (2) engagement, (3) concerns, and (4) autonomy. The second phase discussed the impact of genetic testing on treatment (10 interviews), which revealed 3 major themes: (1) testing features, (2) emotional impact, and (3) treatment outcomes. Overall, parents pursued genetic testing to obtain a clear prognosis, inform treatment decisions, engage with other families, and exercise autonomy. Caregivers felt that early testing is warranted to inform their child’s diagnostic odyssey.
Published: 2022

9. Correction to: Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy

Author: Yun-Fei Bai, Michelle Chiu, Elizabeth S. Chan, Peter Axerio-Cilies, Jie Lu, Linda Huh, Mary B. Connolly, Ilaria Guella, Matthew J. Farrer, Zhi-Qing David Xu, Lidong Liu, Michelle Demos, and Yu Tian Wang
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Following publication of the original article [1], the authors reported errors in Figure 4.
Published: 2020
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10. Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy

Author: Michelle Demos, Ilaria Guella, Conrado DeGuzman, Marna B. McKenzie, Sarah E. Buerki, Daniel M. Evans, Eric B. Toyota, Cyrus Boelman, Linda L. Huh, Anita Datta, Aspasia Michoulas, Kathryn Selby, Bruce H. Bjornson, Gabriella Horvath, Elena Lopez-Rangel, Clara D. M. van Karnebeek, Ramona Salvarinova, Erin Slade, Patrice Eydoux, Shelin Adam, Margot I. Van Allen, Tanya N. Nelson, Corneliu Bolbocean, Mary B. Connolly, and Matthew J. Farrer
Subjects: targeted WES, early-onset epilepsy, diagnostic yield, cost estimation, Canada, Neurology. Diseases of the nervous system, RC346-429
Abstract: Targeted whole-exome sequencing (WES) is a powerful diagnostic tool for a broad spectrum of heterogeneous neurological disorders. Here, we aim to examine the impact on diagnosis, treatment and cost with early use of targeted WES in early-onset epilepsy. WES was performed on 180 patients with early-onset epilepsy (≤5 years) of unknown cause. Patients were classified as Retrospective (epilepsy diagnosis >6 months) or Prospective (epilepsy diagnosis
Published: 2019
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11. A longitudinal cohort study of mediators of health‐related quality of life after pediatric epilepsy surgery or medical treatment

Author: Mary Lou Smith, Klajdi Puka, Kathy N. Speechley, Mark A. Ferro, Mary B. Connolly, Philippe Major, Anne Gallagher, Salah Almubarak, Simona Hasal, Rajesh Ramachandrannair, Andrea Andrade, Qi Xu, Edward Leung, O. Carter Snead, and Elysa Widjaja
Subjects: Neurology, Neurology (clinical)
Published: 2023

12. Defining transformation events for gene drive in species complexes

Author: John B. Connolly
Abstract: Engineered gene drives (EGDs) that allow the super-Mendelian inheritance of genetic traits could one day be used to reduce the vectorial capacity of Anopheles species that transmit human malaria in Africa. Many Anopheles species belong to complexes of closely related sibling species that can produce fertile interspecific hybrid females. In cases where the genomic target locus of the EGD is conserved amongst sibling species from the same complex as the released target species, it would therefore be plausible that the EGD could be vertically transmitted from the target species to sibling species by interspecific mating. To differentiate genetically modified organisms, the term ‘transformation event’ is used, based on the specific genomic location of the transgenic construct, as a result of random genomic integration. In contrast, an EGD is generated via its precise and reproducible insertion in its specific genomic target locus. These considerations pose two key questions for the use of EGD in species complexes: (i) what does the definition of “transformation event” mean in the context of vertical gene drive transfer of the EGD to sibling species in species complexes and (ii) does de novo transformation of an EGD into a sibling species constitute the same transformation event as introgression by backcrossing into a sibling species of an EGD that had been originally transformed in the target species? While definitions of the term transformation event that have been provided by national and intergovernmental organisations are somewhat ambiguous, they do provide scope for broad interpretation of vertical gene drive transfer of a specific EGD to different sibling species of the target species as the same transformation event. There also appears to be some consensus that definitions of transformation event support the notion that de novo transformations of an EGD in sibling species constitute the same transformation events as introgression by backcrossing into sibling species of an EGD that had been originally inserted in the target species.
Published: 2023

13. Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study

Author: Hamish J.C. McAuley, Rachael A. Evans, Charlotte E. Bolton, Christopher E. Brightling, James D. Chalmers, Annemarie B. Docherty, Omer Elneima, Paul L. Greenhaff, Ayushman Gupta, Victoria C. Harris, Ewen M. Harrison, Ling-Pei Ho, Alex Horsley, Linzy Houchen-Wolloff, Caroline J. Jolley, Olivia C. Leavy, Nazir I. Lone, William D-C Man, Michael Marks, Dhruv Parekh, Krisnah Poinasamy, Jennifer K. Quint, Betty Raman, Matthew Richardson, Ruth M. Saunders, Marco Sereno, Aarti Shikotra, Amisha Singapuri, Sally J. Singh, Michael Steiner, Ai Lyn Tan, Louise V. Wain, Carly Welch, Julie Whitney, Miles D. Witham, Janet Lord, Neil J. Greening, K. Abel, H. Adamali, D. Adeloye, O. Adeyemi, R. Adrego, L.A. Aguilar Jimenez, S. Ahmad, N. Ahmad Haider, R. Ahmed, N. Ahwireng, M. Ainsworth, B. Al-Sheklly, A. Alamoudi, M. Ali, M. Aljaroof, A.M. All, L. Allan, R.J. Allen, L. Allerton, L. Allsop, P. Almeida, D. Altmann, M. Alvarez Corral, S. Amoils, D. Anderson, C. Antoniades, G. Arbane, A. Arias, C. Armour, L. Armstrong, N. Armstrong, D. Arnold, H. Arnold, A. Ashish, A. Ashworth, M. Ashworth, S. Aslani, H. Assefa-Kebede, C. Atkin, P. Atkin, R. Aul, H. Aung, L. Austin, C. Avram, A. Ayoub, M. Babores, R. Baggott, J. Bagshaw, D. Baguley, L. Bailey, J.K. Baillie, S. Bain, M. Bakali, M. Bakau, E. Baldry, D. Baldwin, M. Baldwin, C. Ballard, A. Banerjee, B. Bang, R.E. Barker, L. Barman, S. Barratt, F. Barrett, D. Basire, N. Basu, M. Bates, A. Bates, R. Batterham, H. Baxendale, H. Bayes, M. Beadsworth, P. Beckett, M. Beggs, M. Begum, P. Beirne, D. Bell, R. Bell, K. Bennett, E. Beranova, A. Bermperi, A. Berridge, C. Berry, S. Betts, E. Bevan, K. Bhui, M. Bingham, K. Birchall, L. Bishop, K. Bisnauthsing, J. Blaikely, A. Bloss, A. Bolger, C.E. Bolton, J. Bonnington, A. Botkai, C. Bourne, M. Bourne, K. Bramham, L. Brear, G. Breen, J. Breeze, A. Briggs, E. Bright, C.E. Brightling, S. Brill, K. Brindle, L. Broad, A. Broadley, C. Brookes, M. Broome, A. Brown, J. Brown, J.S. Brown, M. Brown, V. Brown, T. Brugha, N. Brunskill, M. Buch, P. Buckley, A. Bularga, E. Bullmore, L. Burden, T. Burdett, D. Burn, G. Burns, A. Burns, J. Busby, R. Butcher, A. Butt, S. Byrne, P. Cairns, P.C. Calder, E. Calvelo, H. Carborn, B. Card, C. Carr, L. Carr, G. Carson, P. Carter, A. Casey, M. Cassar, J. Cavanagh, M. Chablani, T. Chalder, J.D. Chalmers, R.C. Chambers, F. Chan, K.M. Channon, K. Chapman, A. Charalambou, N. Chaudhuri, A. Checkley, J. Chen, Y. Cheng, L. Chetham, C. Childs, E.R. Chilvers, H. Chinoy, A. Chiribiri, K. Chong-James, G. Choudhury, N. Choudhury, P. Chowienczyk, C. Christie, M. Chrystal, D. Clark, C. Clark, J. Clarke, S. Clohisey, G. Coakley, Z. Coburn, S. Coetzee, J. Cole, C. Coleman, F. Conneh, D. Connell, B. Connolly, L. Connor, A. Cook, B. Cooper, J. Cooper, S. Cooper, D. Copeland, T. Cosier, M. Coulding, C. Coupland, E. Cox, T. Craig, P. Crisp, D. Cristiano, M.G. Crooks, A. Cross, I. Cruz, P. Cullinan, D. Cuthbertson, L. Daines, M. Dalton, P. Daly, A. Daniels, P. Dark, J. Dasgin, A. David, C. David, E. Davies, F. Davies, G. Davies, G.A. Davies, K. Davies, M.J. Davies, J. Dawson, E. Daynes, A. De Soyza, B. Deakin, A. Deans, C. Deas, J. Deery, S. Defres, A. Dell, K. Dempsey, E. Denneny, J. Dennis, A. Dewar, R. Dharmagunawardena, N. Diar-Bakerly, C. Dickens, A. Dipper, S. Diver, S.N. Diwanji, M. Dixon, R. Djukanovic, H. Dobson, S.L. Dobson, A.B. Docherty, A. Donaldson, T. Dong, N. Dormand, A. Dougherty, R. Dowling, S. Drain, K. Draxlbauer, K. Drury, H.J.C. Drury, P. Dulawan, A. Dunleavy, S. Dunn, C. Dupont, J. Earley, N. Easom, C. Echevarria, S. Edwards, C. Edwardson, H. El-Taweel, A. Elliott, K. Elliott, Y. Ellis, A. Elmer, O. Elneima, D. Evans, H. Evans, J. Evans, R. Evans, R.A. Evans, R.I. Evans, T. Evans, C. Evenden, L. Evison, L. Fabbri, S. Fairbairn, A. Fairman, K. Fallon, D. Faluyi, C. Favager, T. Fayzan, J. Featherstone, T. Felton, J. Finch, S. Finney, J. Finnigan, L. Finnigan, H. Fisher, S. Fletcher, R. Flockton, M. Flynn, H. Foot, D. Foote, A. Ford, D. Forton, E. Fraile, C. Francis, R. Francis, S. Francis, A. Frankel, E. Fraser, R. Free, N. French, X. Fu, J. Fuld, J. Furniss, L. Garner, N. Gautam, J.R. Geddes, J. George, P. George, M. Gibbons, M. Gill, L. Gilmour, F. Gleeson, J. Glossop, S. Glover, N. Goodman, C. Goodwin, B. Gooptu, H. Gordon, T. Gorsuch, M. Greatorex, P.L. Greenhaff, W. Greenhalf, A. Greenhalgh, N.J. Greening, J. Greenwood, H. Gregory, R. Gregory, D. Grieve, D. Griffin, L. Griffiths, A.-M. Guerdette, B. Guillen Guio, M. Gummadi, A. Gupta, S. Gurram, E. Guthrie, Z. Guy, H.H. Henson, K. Hadley, A. Haggar, K. Hainey, B. Hairsine, P. Haldar, I. Hall, L. Hall, M. Halling-Brown, R. Hamil, A. Hancock, K. Hancock, N.A. Hanley, S. Haq, H.E. Hardwick, E. Hardy, T. Hardy, B. Hargadon, K. Harrington, E. Harris, V.C. Harris, E.M. Harrison, P. Harrison, N. Hart, A. Harvey, M. Harvey, M. Harvie, L. Haslam, M. Havinden-Williams, J. Hawkes, N. Hawkings, J. Haworth, A. Hayday, M. Haynes, J. Hazeldine, T. Hazelton, L.G. Heaney, C. Heeley, J.L. Heeney, M. Heightman, S. Heller, M. Henderson, L. Hesselden, M. Hewitt, V. Highett, T. Hillman, T. Hiwot, L.P. Ho, A. Hoare, M. Hoare, J. Hockridge, P. Hogarth, A. Holbourn, S. Holden, L. Holdsworth, D. Holgate, M. Holland, L. Holloway, K. Holmes, M. Holmes, B. Holroyd-Hind, L. Holt, A. Hormis, A. Horsley, A. Hosseini, M. Hotopf, L. Houchen-Wolloff, K. Howard, L.S. Howard, A. Howell, E. Hufton, A.D. Hughes, J. Hughes, R. Hughes, A. Humphries, N. Huneke, E. Hurditch, J. Hurst, M. Husain, T. Hussell, J. Hutchinson, W. Ibrahim, F. Ilyas, J. Ingham, L. Ingram, D. Ionita, K. Isaacs, K. Ismail, T. Jackson, J. Jacob, W.Y. James, W. Jang, C. Jarman, I. Jarrold, H. Jarvis, R. Jastrub, B. Jayaraman, R.G. Jenkins, P. Jezzard, K. Jiwa, C. Johnson, S. Johnson, D. Johnston, C.J. Jolley, D. Jones, G. Jones, H. Jones, I. Jones, L. Jones, M.G. Jones, S. Jones, S. Jose, T. Kabir, G. Kaltsakas, V. Kamwa, N. Kanellakis, S. Kaprowska, Z. Kausar, N. Keenan, S. Kelly, G. Kemp, S. Kerr, H. Kerslake, A.L. Key, F. Khan, K. Khunti, S. Kilroy, B. King, C. King, L. Kingham, J. Kirk, P. Kitterick, P. Klenerman, L. Knibbs, S. Knight, A. Knighton, O. Kon, S. Kon, S.S. Kon, S. Koprowska, A. Korszun, I. Koychev, C. Kurasz, P. Kurupati, C. Laing, H. Lamlum, G. Landers, C. Langenberg, D. Lasserson, L. Lavelle-Langham, A. Lawrie, C. Lawson, A. Layton, A. Lea, O.C. Leavy, D. Lee, J.-H. Lee, E. Lee, K. Leitch, R. Lenagh, D. Lewis, J. Lewis, K.E. Lewis, V. Lewis, N. Lewis-Burke, X. Li, T. Light, L. Lightstone, W. Lilaonitkul, L. Lim, S. Linford, A. Lingford-Hughes, M. Lipman, K. Liyanage, A. Lloyd, S. Logan, D. Lomas, N.I. Lone, R. Loosley, J.M. Lord, H. Lota, W. Lovegrove, A. Lucey, E. Lukaschuk, A. Lye, C. Lynch, S. MacDonald, G. MacGowan, I. Macharia, J. Mackie, L. Macliver, S. Madathil, G. Madzamba, N. Magee, M.M. Magtoto, N. Mairs, N. Majeed, E. Major, F. Malein, M. Malim, G. Mallison, W. D-C Man, S. Mandal, K. Mangion, C. Manisty, R. Manley, K. March, S. Marciniak, P. Marino, M. Mariveles, M. Marks, E. Marouzet, S. Marsh, B. Marshall, M. Marshall, J. Martin, A. Martineau, L.M. Martinez, N. Maskell, D. Matila, W. Matimba-Mupaya, L. Matthews, A. Mbuyisa, S. McAdoo, H. McAllister-Williams, A. McArdle, P. McArdle, D. McAulay, G.P. McCann, J. McCormick, W. McCormick, P. McCourt, L. McGarvey, C. McGee, K. Mcgee, J. McGinness, K. McGlynn, A. McGovern, H. McGuinness, I.B. McInnes, J. McIntosh, E. McIvor, K. McIvor, L. McLeavey, A. McMahon, M.J. McMahon, L. McMorrow, T. Mcnally, M. McNarry, J. McNeill, A. McQueen, H. McShane, C. Mears, C. Megson, S. Megson, P. Mehta, J. Meiring, L. Melling, M. Mencias, D. Menzies, M. Merida Morillas, A. Michael, C. Miller, L. Milligan, C. Mills, G. Mills, N.L. Mills, L. Milner, S. Misra, J. Mitchell, A. Mohamed, N. Mohamed, S. Mohammed, P.L. Molyneaux, W. Monteiro, S. Moriera, A. Morley, L. Morrison, R. Morriss, A. Morrow, A.J. Moss, P. Moss, K. Motohashi, N. Msimanga, E. Mukaetova-Ladinska, U. Munawar, J. Murira, U. Nanda, H. Nassa, M. Nasseri, A. Neal, R. Needham, P. Neill, S. Neubauer, D.E. Newby, H. Newell, T. Newman, J. Newman, A. Newton-Cox, T. Nicholson, D. Nicoll, A. Nikolaidis, C.M. Nolan, M.J. Noonan, C. Norman, P. Novotny, J. Nunag, L. Nwafor, U. Nwanguma, J. Nyaboko, C. O'Brien, K. O'Donnell, D. O'Regan, L. O’Brien, N. Odell, G. Ogg, O. Olaosebikan, C. Oliver, Z. Omar, P.J.M. Openshaw, L. Orriss-Dib, L. Osborne, R. Osbourne, M. Ostermann, C. Overton, J. Owen, J. Oxton, J. Pack, E. Pacpaco, S. Paddick, S. Painter, A. Pakzad, S. Palmer, P. Papineni, K. Paques, K. Paradowski, M. Pareek, D. Parekh, H. Parfrey, C. Pariante, S. Parker, M. Parkes, J. Parmar, S. Patale, B. Patel, M. Patel, S. Patel, D. Pattenadk, M. Pavlides, S. Payne, L. Pearce, J.E. Pearl, D. Peckham, J. Pendlebury, Y. Peng, C. Pennington, I. Peralta, E. Perkins, Z. Peterkin, T. Peto, N. Petousi, J. Petrie, P. Pfeffer, J. Phipps, J. Pimm, K. Piper Hanley, R. Pius, H. Plant, S. Plein, T. Plekhanova, M. Plowright, K. Poinasamy, O. Polgar, L. Poll, J.C. Porter, J. Porter, S. Portukhay, N. Powell, A. Prabhu, J. Pratt, A. Price, C. Price, D. Price, L. Price, A. Prickett, J. Propescu, S. Prosper, S. Pugmire, S. Quaid, J. Quigley, J. Quint, H. Qureshi, I.N. Qureshi, K. Radhakrishnan, N.M. Rahman, M. Ralser, B. Raman, A. Ramos, H. Ramos, J. Rangeley, B. Rangelov, L. Ratcliffe, P. Ravencroft, A. Reddington, R. Reddy, A. Reddy, H. Redfearn, D. Redwood, A. Reed, M. Rees, T. Rees, K. Regan, W. Reynolds, C. Ribeiro, A. Richards, E. Richardson, M. Richardson, P. Rivera-Ortega, K. Roberts, E. Robertson, E. Robinson, L. Robinson, L. Roche, C. Roddis, J. Rodger, A. Ross, G. Ross, J. Rossdale, A. Rostron, A. Rowe, A. Rowland, J. Rowland, M.J. Rowland, S.L. Rowland-Jones, K. Roy, M. Roy, I. Rudan, R. Russell, E. Russell, G. Saalmink, R. Sabit, E.K. Sage, T. Samakomva, N. Samani, C. Sampson, K. Samuel, R. Samuel, A. Sanderson, E. Sapey, D. Saralaya, J. Sargant, C. Sarginson, T. Sass, N. Sattar, K. Saunders, R.M. Saunders, P. Saunders, L.C. Saunders, H. Savill, W. Saxon, A. Sayer, J. Schronce, W. Schwaeble, J.T. Scott, K. Scott, N. Selby, M.G. Semple, M. Sereno, T.A. Sewell, A. Shah, K. Shah, P. Shah, M. Shankar-Hari, M. Sharma, C. Sharpe, M. Sharpe, S. Shashaa, A. Shaw, K. Shaw, V. Shaw, A. Sheikh, S. Shelton, L. Shenton, K. Shevket, A. Shikotra, J. Short, S. Siddique, S. Siddiqui, J. Sidebottom, L. Sigfrid, G. Simons, J. Simpson, N. Simpson, A. Singapuri, C. Singh, S. Singh, S.J. Singh, D. Sissons, J. Skeemer, K. Slack, A. Smith, D. Smith, S. Smith, J. Smith, L. Smith, M. Soares, T.S. Solano, R. Solly, A.R. Solstice, T. Soulsby, D. Southern, D. Sowter, M. Spears, L.G. Spencer, F. Speranza, L. Stadon, S. Stanel, N. Steele, M. Steiner, D. Stensel, G. Stephens, L. Stephenson, M. Stern, I. Stewart, R. Stimpson, S. Stockdale, J. Stockley, W. Stoker, R. Stone, W. Storrar, A. Storrie, K. Storton, E. Stringer, S. Strong-Sheldrake, N. Stroud, C. Subbe, C.L. Sudlow, Z. Suleiman, C. Summers, C. Summersgill, D. Sutherland, D.L. Sykes, R. Sykes, N. Talbot, A.L. Tan, L. Tarusan, V. Tavoukjian, A. Taylor, C. Taylor, J. Taylor, A. Te, H. Tedd, C.J. Tee, J. Teixeira, H. Tench, S. Terry, S. Thackray-Nocera, F. Thaivalappil, B. Thamu, D. Thickett, C. Thomas, D.C. Thomas, S. Thomas, A.K. Thomas, T. Thomas-Woods, T. Thompson, A.A.R. Thompson, T. Thornton, M. Thorpe, R.S. Thwaites, J. Tilley, N. Tinker, G.F. Tiongson, M. Tobin, J. Tomlinson, C. Tong, M. Toshner, R. Touyz, K.A. Tripp, E. Tunnicliffe, A. Turnbull, E. Turner, S. Turner, V. Turner, K. Turner, S. Turney, L. Turtle, H. Turton, J. Ugoji, R. Ugwuoke, R. Upthegrove, J. Valabhji, M. Ventura, J. Vere, C. Vickers, B. Vinson, E. Wade, P. Wade, L.V. Wain, T. Wainwright, L.O. Wajero, S. Walder, S. Walker, E. Wall, T. Wallis, S. Walmsley, J.A. Walsh, S. Walsh, L. Warburton, T.J.C. Ward, K. Warwick, H. Wassall, S. Waterson, E. Watson, L. Watson, J. Watson, J. Weir McCall, C. Welch, H. Welch, B. Welsh, S. Wessely, S. West, H. Weston, H. Wheeler, S. White, V. Whitehead, J. Whitney, S. Whittaker, B. Whittam, V. Whitworth, A. Wight, J. Wild, M. Wilkins, D. Wilkinson, B. Williams, N. Williams, J. Williams, S.A. Williams-Howard, M. Willicombe, G. Willis, J. Willoughby, A. Wilson, D. Wilson, I. Wilson, N. Window, M. Witham, R. Wolf-Roberts, C. Wood, F. Woodhead, J. Woods, D.G. Wootton, J. Wormleighton, J. Worsley, D. Wraith, C. Wrey Brown, C. Wright, L. Wright, S. Wright, J. Wyles, I. Wynter, M. Xu, N. Yasmin, S. Yasmin, T. Yates, K.P. Yip, B. Young, S. Young, A. Young, A.J. Yousuf, A. Zawia, L. Zeidan, B. Zhao, B. Zheng, O. Zongo, PHOSP-COVID Study Collaborative Group, Group, PHOSP-COVID Study Collaborative, and Apollo - University of Cambridge Repository
Subjects: Medicine(all), Fried's frailty phenotype, Hospitalisation, COVID-19, General Medicine, Long-COVID, Physical frailty
Abstract: Data sharing statement: The protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online at https://www.phosp.org/ Copyright © 2023 The Author(s). Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research. The study was funded with grants from UK Research and Innovation (MR/V027859/1) and The National Institute of Health Research (COV0319). This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the study at all of the 40 NHS trusts and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland, and Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. The authors would also like to acknowledge the support of the eDRIS Team (Public Health Scotland) for their involvement in obtaining approvals, provisioning and linking data and the use of the secure analytical platform within the National Safe Haven.
Published: 2023

14. Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Author: Callum Jackson, Iain D Stewart, Tatiana Plekhanova, Peter S Cunningham, Andrew L Hazel, Bashar Al-Sheklly, Raminder Aul, Charlotte E Bolton, Trudie Chalder, James D Chalmers, Nazia Chaudhuri, Annemarie B Docherty, Gavin Donaldson, Charlotte L Edwardson, Omer Elneima, Neil J Greening, Neil A Hanley, Victoria C Harris, Ewen M Harrison, Ling-Pei Ho, Linzy Houchen-Wolloff, Luke S Howard, Caroline J Jolley, Mark G Jones, Olivia C Leavy, Keir E Lewis, Nazir I Lone, Michael Marks, Hamish J C McAuley, Melitta A McNarry, Brijesh V Patel, Karen Piper-Hanley, Krisnah Poinasamy, Betty Raman, Matthew Richardson, Pilar Rivera-Ortega, Sarah L Rowland-Jones, Alex V Rowlands, Ruth M Saunders, Janet T Scott, Marco Sereno, Ajay M Shah, Aarti Shikotra, Amisha Singapuri, Stefan C Stanel, Mathew Thorpe, Daniel G Wootton, Thomas Yates, R Gisli Jenkins, Sally J Singh, William D-C Man, Christopher E Brightling, Louise V Wain, Joanna C Porter, A A Roger Thompson, Alex Horsley, Philip L Molyneaux, Rachael A Evans, Samuel E Jones, Martin K Rutter, John F Blaikley, C Jackson, I D Stewart, T Plekhanova, P S Cunningham, A L Hazel, B Al-Sheklly, R Aul, C E Bolton, T Chalder, J D Chalmers, N Chaudhuri, A B Docherty, G Donaldson, C L Edwardson, O Elneima, N J Greening, N A Hanley, V C Harris, E M Harrison, L-P Ho, L Houchen-Wolloff, L S Howard, C J Jolley, M G Jones, O C Leavy, K E Lewis, N I Lone, M Marks, H J C McAuley, M A McNarry, B Patel, K Piper-Hanley, K Poinasamy, B Raman, M Richardson, P Rivera-Ortega, S L Rowland-Jones, A V Rowlands, R M Saunders, J T Scott, M Sereno, A M Shah, A Shikotra, A Singapuri, S C Stanel, M Thorpe, D G Wootton, T Yates, G Jenkins, S J Singh, W D-C Man, C E Brightling, L V Wain, J C Porter, R Thompson, A Horsley, P L Molyneaux, R A Evans, S E Jones, M K Rutter, J F Blaikley, K Abel, H Adamali, D Adeloye, O Adeyemi, R Adrego, L A Aguilar Jimenez, S Ahmad, N Ahmad Haider, R Ahmed, N Ahwireng, M Ainsworth, A Alamoudi, M Ali, M Aljaroof, AM All, L Allan, R J Allen, L Allerton, L Allsop, P Almeida, D Altmann, M Alvarez Corral, S Amoils, D Anderson, C Antoniades, G Arbane, A Arias, C Armour, L Armstrong, N Armstrong, D Arnold, H Arnold, A Ashish, A Ashworth, M Ashworth, S Aslani, H Assefa-Kebede, C Atkin, P Atkin, H Aung, L Austin, C Avram, A Ayoub, M Babores, R Baggott, J Bagshaw, D Baguley, L Bailey, J K Baillie, S Bain, M Bakali, M Bakau, E Baldry, D Baldwin, M Baldwin, C Ballard, A Banerjee, B Bang, R E Barker, L Barman, S Barratt, F Barrett, D Basire, N Basu, M Bates, A Bates, R Batterham, H Baxendale, H Bayes, M Beadsworth, P Beckett, M Beggs, M Begum, P Beirne, D Bell, R Bell, K Bennett, E Beranova, A Bermperi, A Berridge, C Berry, S Betts, E Bevan, K Bhui, M Bingham, K Birchall, L Bishop, K Bisnauthsing, J Blaikely, A Bloss, A Bolger, J Bonnington, A Botkai, C Bourne, M Bourne, K Bramham, L Brear, G Breen, J Breeze, A Briggs, E Bright, S Brill, K Brindle, L Broad, A Broadley, C Brookes, M Broome, A Brown, J Brown, J S Brown, M Brown, V Brown, T Brugha, N Brunskill, M Buch, P Buckley, A Bularga, E Bullmore, L Burden, T Burdett, D Burn, G Burns, A Burns, J Busby, R Butcher, A Butt, S Byrne, P Cairns, P C Calder, E Calvelo, H Carborn, B Card, C Carr, L Carr, G Carson, P Carter, A Casey, M Cassar, J Cavanagh, M Chablani, R C Chambers, F Chan, K M Channon, K Chapman, A Charalambou, A Checkley, J Chen, Y Cheng, L Chetham, C Childs, E R Chilvers, H Chinoy, A Chiribiri, K Chong-James, G Choudhury, N Choudhury, P Chowienczyk, C Christie, M Chrystal, D Clark, C Clark, J Clarke, S Clohisey, G Coakley, Z Coburn, S Coetzee, J Cole, C Coleman, F Conneh, D Connell, B Connolly, L Connor, A Cook, B Cooper, J Cooper, S Cooper, D Copeland, T Cosier, M Coulding, C Coupland, E Cox, T Craig, P Crisp, D Cristiano, M G Crooks, A Cross, I Cruz, P Cullinan, D Cuthbertson, L Daines, M Dalton, P Daly, A Daniels, P Dark, J Dasgin, A David, C David, E Davies, F Davies, G Davies, G A Davies, K Davies, M J Davies, J Dawson, E Daynes, A De Soyza, B Deakin, A Deans, C Deas, J Deery, S Defres, A Dell, K Dempsey, E Denneny, J Dennis, A Dewar, R Dharmagunawardena, N Diar-Bakerly, C Dickens, A Dipper, S Diver, S N Diwanji, M Dixon, R Djukanovic, H Dobson, S L Dobson, A Donaldson, T Dong, N Dormand, A Dougherty, R Dowling, S Drain, K Draxlbauer, K Drury, P Dulawan, A Dunleavy, S Dunn, C Dupont, J Earley, N Easom, C Echevarria, S Edwards, C Edwardson, H El-Taweel, A Elliott, K Elliott, Y Ellis, A Elmer, D Evans, H Evans, J Evans, R Evans, R I Evans, T Evans, C Evenden, L Evison, L Fabbri, S Fairbairn, A Fairman, K Fallon, D Faluyi, C Favager, T Fayzan, J Featherstone, T Felton, J Finch, S Finney, J Finnigan, L Finnigan, H Fisher, S Fletcher, R Flockton, M Flynn, H Foot, D Foote, A Ford, D Forton, E Fraile, C Francis, R Francis, S Francis, A Frankel, E Fraser, R Free, N French, X Fu, J Fuld, J Furniss, L Garner, N Gautam, J R Geddes, J George, P M George, M Gibbons, M Gill, L Gilmour, F Gleeson, J Glossop, S Glover, N Goodman, C Goodwin, B Gooptu, H Gordon, T Gorsuch, M Greatorex, P L Greenhaff, W Greenhalf, A Greenhalgh, J Greenwood, H Gregory, R Gregory, D Grieve, D Griffin, L Griffiths, A-M Guerdette, B Guillen Guio, M Gummadi, A Gupta, S Gurram, E Guthrie, Z Guy, H Henson, K Hadley, A Haggar, K Hainey, B Hairsine, P Haldar, I Hall, L Hall, M Halling-Brown, R Hamil, A Hancock, K Hancock, S Haq, H E Hardwick, E Hardy, T Hardy, B Hargadon, K Harrington, E Harris, P Harrison, N Hart, A Harvey, M Harvey, M Harvie, L Haslam, M Havinden-Williams, J Hawkes, N Hawkings, J Haworth, A Hayday, M Haynes, J Hazeldine, T Hazelton, L G Heaney, C Heeley, J L Heeney, M Heightman, S Heller, M Henderson, L Hesselden, M Hewitt, V Highett, T Hillman, T Hiwot, A Hoare, M Hoare, J Hockridge, P Hogarth, A Holbourn, S Holden, L Holdsworth, D Holgate, M Holland, L Holloway, K Holmes, M Holmes, B Holroyd-Hind, L Holt, A Hormis, A Hosseini, M Hotopf, K Howard, A Howell, E Hufton, A D Hughes, J Hughes, R Hughes, A Humphries, N Huneke, E Hurditch, J Hurst, M Husain, T Hussell, J Hutchinson, W Ibrahim, F Ilyas, J Ingham, L Ingram, D Ionita, K Isaacs, K Ismail, T Jackson, J Jacob, W Y James, W Jang, C Jarman, I Jarrold, H Jarvis, R Jastrub, B Jayaraman, R G Jenkins, P Jezzard, K Jiwa, C Johnson, S Johnson, D Johnston, D Jones, G Jones, H Jones, I Jones, L Jones, S Jones, S Jose, T Kabir, G Kaltsakas, V Kamwa, N Kanellakis, S Kaprowska, Z Kausar, N Keenan, S Kelly, G Kemp, S Kerr, H Kerslake, A L Key, F Khan, K Khunti, S Kilroy, B King, C King, L Kingham, J Kirk, P Kitterick, P Klenerman, L Knibbs, S Knight, A Knighton, O Kon, S Kon, S S Kon, S Koprowska, A Korszun, I Koychev, C Kurasz, P Kurupati, C Laing, H Lamlum, G Landers, C Langenberg, D Lasserson, L Lavelle-Langham, A Lawrie, C Lawson, A Layton, A Lea, D Lee, J-H Lee, E Lee, K Leitch, R Lenagh, D Lewis, J Lewis, V Lewis, N Lewis-Burke, X Li, T Light, L Lightstone, W Lilaonitkul, L Lim, S Linford, A Lingford-Hughes, M Lipman, K Liyanage, A Lloyd, S Logan, D Lomas, R Loosley, J M Lord, H Lota, W Lovegrove, A Lucey, E Lukaschuk, A Lye, C Lynch, S MacDonald, G MacGowan, I Macharia, J Mackie, L Macliver, S Madathil, G Madzamba, N Magee, M M Magtoto, N Mairs, N Majeed, E Major, F Malein, M Malim, G Mallison, S Mandal, K Mangion, C Manisty, R Manley, K March, S Marciniak, P Marino, M Mariveles, E Marouzet, S Marsh, B Marshall, M Marshall, J Martin, A Martineau, L M Martinez, N Maskell, D Matila, W Matimba-Mupaya, L Matthews, A Mbuyisa, S McAdoo, H McAllister-Williams, A McArdle, P McArdle, D McAulay, G P McCann, J McCormick, W McCormick, P McCourt, L McGarvey, C McGhee, K Mcgee, J McGinness, K McGlynn, A McGovern, H McGuinness, I B McInnes, J McIntosh, E McIvor, K McIvor, L McLeavey, A McMahon, M J McMahon, L McMorrow, T Mcnally, M McNarry, J McNeill, A McQueen, H McShane, C Mears, C Megson, S Megson, P Mehta, J Meiring, L Melling, M Mencias, D Menzies, M Merida Morillas, A Michael, C Miller, L Milligan, C Mills, G Mills, N L Mills, L Milner, S Misra, J Mitchell, A Mohamed, N Mohamed, S Mohammed, W Monteiro, S Moriera, A Morley, L Morrison, R Morriss, A Morrow, A J Moss, P Moss, K Motohashi, N Msimanga, E Mukaetova-Ladinska, U Munawar, J Murira, U Nanda, H Nassa, M Nasseri, A Neal, R Needham, P Neill, S Neubauer, D E Newby, H Newell, T Newman, J Newman, A Newton-Cox, T Nicholson, D Nicoll, A Nikolaidis, C M Nolan, M J Noonan, C Norman, P Novotny, J Nunag, L Nwafor, U Nwanguma, J Nyaboko, C O'Brien, K O'Donnell, D O'Regan, L O'Brien, N Odell, G Ogg, O Olaosebikan, C Oliver, Z Omar, P J M Openshaw, L Orriss-Dib, L Osborne, R Osbourne, M Ostermann, C Overton, J Owen, J Oxton, J Pack, E Pacpaco, S Paddick, S Painter, A Pakzad, S Palmer, P Papineni, K Paques, K Paradowski, M Pareek, D Parekh, H Parfrey, C Pariante, S Parker, M Parkes, J Parmar, S Patale, M Patel, S Patel, D Pattenadk, M Pavlides, S Payne, L Pearce, J E Pearl, D Peckham, J Pendlebury, Y Peng, C Pennington, I Peralta, E Perkins, Z Peterkin, T Peto, N Petousi, J Petrie, P Pfeffer, J Phipps, J Pimm, R Pius, H Plant, S Plein, M Plowright, O Polgar, L Poll, J Porter, S Portukhay, N Powell, A Prabhu, J Pratt, A Price, C Price, D Price, L Price, A Prickett, J Propescu, S Prosper, S Pugmire, S Quaid, J Quigley, J Quint, H Qureshi, I N Qureshi, K Radhakrishnan, N M Rahman, M Ralser, A Ramos, H Ramos, J Rangeley, B Rangelov, L Ratcliffe, P Ravencroft, A Reddington, R Reddy, A Reddy, H Redfearn, D Redwood, A Reed, M Rees, T Rees, K Regan, W Reynolds, C Ribeiro, A Richards, E Richardson, K Roberts, E Robertson, E Robinson, L Robinson, L Roche, C Roddis, J Rodger, A Ross, G Ross, J Rossdale, A Rostron, A Rowe, A Rowland, J Rowland, M J Rowland, K Roy, M Roy, I Rudan, R Russell, E Russell, G Saalmink, R Sabit, E K Sage, T Samakomva, N Samani, C Sampson, K Samuel, R Samuel, A Sanderson, E Sapey, D Saralaya, J Sargent, C Sarginson, T Sass, N Sattar, K Saunders, P Saunders, L C Saunders, H Savill, W Saxon, A Sayer, J Schronce, W Schwaeble, K Scott, N Selby, M G Semple, T A Sewell, K Shah, P Shah, M Shankar-Hari, M Sharma, C Sharpe, M Sharpe, S Shashaa, A Shaw, K Shaw, V Shaw, A Sheikh, S Shelton, L Shenton, K Shevket, J Short, S Siddique, S Siddiqui, J Sidebottom, L Sigfrid, G Simons, J Simpson, N Simpson, C Singh, D Sissons, J Skeemer, K Slack, A Smith, D Smith, S Smith, J Smith, L Smith, M Soares, T S Solano, R Solly, A R Solstice, T Soulsby, D Southern, D Sowter, M Spears, L G Spencer, F Speranza, L Stadon, S Stanel, N Steele, M Steiner, D Stensel, G Stephens, L Stephenson, M Stern, R Stimpson, S Stockdale, J Stockley, W Stoker, R Stone, W Storrar, A Storrie, K Storton, E Stringer, S Strong-Sheldrake, N Stroud, C Subbe, C L Sudlow, Z Suleiman, C Summers, C Summersgill, D Sutherland, D L Sykes, R Sykes, N Talbot, A L Tan, L Tarusan, V Tavoukjian, A Taylor, C Taylor, J Taylor, A Te, H Tedd, C J Tee, J Teixeira, H Tench, S Terry, S Thackray-Nocera, F Thaivalappil, B Thamu, D Thickett, C Thomas, D C Thomas, S Thomas, A K Thomas, T Thomas-Woods, T Thompson, A A R Thompson, T Thornton, R S Thwaites, J Tilley, N Tinker, G F Tiongson, M Tobin, J Tomlinson, C Tong, M Toshner, R Touyz, K A Tripp, E Tunnicliffe, A Turnbull, E Turner, S Turner, V Turner, K Turner, S Turney, L Turtle, H Turton, J Ugoji, R Ugwuoke, R Upthegrove, J Valabhji, M Ventura, J Vere, C Vickers, B Vinson, E Wade, P Wade, T Wainwright, L O Wajero, S Walder, S Walker, E Wall, T Wallis, S Walmsley, J A Walsh, S Walsh, L Warburton, T J C Ward, K Warwick, H Wassall, S Waterson, E Watson, L Watson, J Watson, J Weir McCall, C Welch, H Welch, B Welsh, S Wessely, S West, H Weston, H Wheeler, S White, V Whitehead, J Whitney, S Whittaker, B Whittam, V Whitworth, A Wight, J M Wild, M Wilkins, D Wilkinson, B Williams, N Williams, J Williams, S A Williams-Howard, M Willicombe, G Willis, J Willoughby, A Wilson, D Wilson, I Wilson, N Window, M Witham, R Wolf-Roberts, C Wood, F Woodhead, J Woods, J Wormleighton, J Worsley, D Wraith, C Wrey Brown, C Wright, L Wright, S Wright, J Wyles, I Wynter, M Xu, N Yasmin, S Yasmin, K P Yip, B Young, S Young, A Young, A J Yousuf, A Zawia, L Zeidan, B Zhao, B Zheng, O Zongo, Apollo - University of Cambridge Repository, PHOSP-COVID Study Collaborative Group, and Group, PHOSP-COVID Study Collaborative
Subjects: Pulmonary and Respiratory Medicine, PHOSP-COVID Study Collaborative Group
Abstract: Data sharing: The PHOSP-COVID study protocol, consent form, definition, and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online. UK Biobank information can be released once necessary approvals have been obtained. Other data (eg, the R code and protocol) will be made available on reasonable request to the corresponding author. Copyright © 2023 The Author(s). Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.
Published: 2023