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6. Accelerated immune ageing is associated with COVID-19 disease severity

Author

Lord, Janet M., Veenith, Tonny, Sullivan, Jack, Sharma-Oates, Archana, Richter, Alex G., Greening, Neil J., McAuley, Hamish J. C., Evans, Rachael A., Moss, Paul, Moore, Shona C., Turtle, Lance, Gautam, Nandan, Gilani, Ahmed, Bajaj, Manan, Wain, Louise V., Brightling, Christopher, Raman, Betty, Marks, Michael, Singapuri, Amisha, Elneima, Omer, Openshaw, Peter J. M., and Duggal, Niharika A.

Published
2024
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13. Immunesenescence and Compromised Removal of Senescent Cells: Implications for Health in Old Age

Author

Hazeldine, Jon, Lord, Janet M., Rattan, Suresh I.S., Series Editor, Barbagallo, Mario, Editorial Board Member, Çakatay, Ufuk, Editorial Board Member, Fraifeld, Vadim E., Editorial Board Member, Fülöp, Tamàs, Editorial Board Member, Gruber, Jan, Editorial Board Member, Jin, Kunlin, Editorial Board Member, Kaul, Sunil, Editorial Board Member, Kaur, Gurcharan, Editorial Board Member, Le Bourg, Eric, Editorial Board Member, Lopez Lluch, Guillermo, Editorial Board Member, Moskalev, Alexey, Editorial Board Member, Nehlin, Jan, Editorial Board Member, Pawelec, Graham, Editorial Board Member, Rizvi, Syed Ibrahim, Editorial Board Member, Sholl, Jonathan, Editorial Board Member, Stambler, Ilia, Editorial Board Member, Szczerbińska, Katarzyna, Editorial Board Member, Trougakos, Ioannis P., Editorial Board Member, Wadhwa, Renu, Editorial Board Member, Wnuk, Maciej, Editorial Board Member, and Bueno, Valquiria, editor

Published
2022
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16. Symptoms and risk factors for long COVID in non-hospitalized adults

Author

Subramanian, Anuradhaa, Nirantharakumar, Krishnarajah, Hughes, Sarah, Myles, Puja, Williams, Tim, Gokhale, Krishna M., Taverner, Tom, Chandan, Joht Singh, Brown, Kirsty, Simms-Williams, Nikita, Shah, Anoop D., Singh, Megha, Kidy, Farah, Okoth, Kelvin, Hotham, Richard, Bashir, Nasir, Cockburn, Neil, Lee, Siang Ing, Turner, Grace M., Gkoutos, Georgios V., Aiyegbusi, Olalekan Lee, McMullan, Christel, Denniston, Alastair K., Sapey, Elizabeth, Lord, Janet M., Wraith, David C., Leggett, Edward, Iles, Clare, Marshall, Tom, Price, Malcolm J., Marwaha, Steven, Davies, Elin Haf, Jackson, Louise J., Matthews, Karen L., Camaradou, Jenny, Calvert, Melanie, and Haroon, Shamil

Published
2022
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19. The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study.

Author

Thomas, Jarrod L., McGee, Kirsty C., Hossain, Anower, Perkins, Gavin D., Gordon, Anthony C., Young, Duncan, McAuley, Danny, Singer, Mervyn, Lall, Ranjit, Kramaric, Tina, Lord, Janet M., Whitehouse, Tony, Mur, Luis A. J., Veenith, Tonny, Patel, Jaimin, Murphy, Nick, Bangash, Mansoor, Torlinski, Tomasz, Talbot, Nicholas, and Snelson, Catherine

Subjects
ELECTROSPRAY ionization mass spectrometry, SEPTIC shock, METABOLOMIC fingerprinting, SUCCINIC acid, BIOMARKERS
Abstract

Purpose: The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers. Methods: Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient). Metabolite fingerprinting was carried out by flow infusion electrospray ionisation high-resolution mass spectrometry and metabolomic data were analysed using the R-based platform MetaboAnalyst. The metabolites were identified using DIMEdb (dimedb.ibers.aber.ac.uk) from their mass/charge ratios. These metabolomic data were also re-analysed using individual and cluster-level analysis. The individual-level models were adjusted for confounders, such as age, sex, noradrenaline dosage and patient (random effect). Results: Analysis was undertaken at cluster- and individual-level. There were no significant differences in cytokine concentration level between trial arms nor survivors and non-survivors over the duration of the observations from day 1 to day 4. Metabolomic analysis showed some separation in the levels of ceramides and cardiolipins between those who survived and those who died. Following adjusted analysis for confounders, plasma metabolite concentrations remained statistically different between landiolol and standard care arms for succinic acid, l-tryptophan, l-alanine, 2,2,2-trichloroethanol, lactic acid and d-glucose. Conclusions: In a study of ICU patients with established septic shock and a tachycardia, landiolol treatment used to reduce the heart rate from above 95 to a range between 80 and 94 beats per minute did not induce significant cytokine changes. d-Glucose, lactic acid, succinic acid, l-alanine, l-tryptophan and trichloroethanol were pathways that may merit further investigation. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB); ISRCTN registry Identifier: ISRCTN12600919 (https://www.isrctn.com/ISRCTN12600919). [ABSTRACT FROM AUTHOR]

Published
2025
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20. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Author

Abel, K, Adamali, H, Adeloye, D, Adeyemi, O, Adeyemi, F, Ahmad, S, Ahmed, R, Ainsworth, M, Al-Sheklly, B, Alamoudi, A, Aljaroof, M, Allan, L, Allen, R, Alli, A, Altmann, D, Anderson, D, Andrews, M, Angyal, A, Antoniades, C, Arbane, G, Armour, C, Armstrong, N, Armstrong, L, Arnold, H, Arnold, D, Ashworth, M, Ashworth, A, Assefa-Kebede, H, Atkin, P, Atkins, H, Atkins, A, Aul, R, Avram, C, Baggott, R, Baguley, D, Baillie, J K, Bain, S, Bakali, M, Bakau, M, Baldry, E, Baldwin, D, Ballard, C, Bambrough, J, Barker, R E, Barratt, S, Barrett, F, Basire, D, Basu, N, Batterham, R, Baxendale, H, Bayes, H, Bayley, M, Beadsworth, M, Beirne, P, Bell, R, Bell, D, Berry, C, Betts, S, Bhui, K, Bishop, L, Blaikely, J, Bloomfield, C, Bloss, A, Bolger, A, Bolton, C E, Bonnington, J, Botkai, A, Bourne, M, Bourne, C, Bradley, E, Bramham, K, Brear, L, Breen, G, Breeze, J, Briggs, A, Bright, E, Brightling, C E, Brill, S, Brindle, K, Broad, L, Broome, M, Brown, J S, Brown, M, Brown, J, Brown, R, Brown, V, Brown, A, Brugha, T, Brunskill, N, Buch, M, Bularga, A, Bullmore, E, Burn, D, Burns, G, Busby, J, Buttress, A, Byrne, S, Cairns, P, Calder, P C, Calvelo, E, Card, B, Carr, L, Carson, G, Carter, P, Cavanagh, J, Chalder, T, Chalmers, J D, Chambers, R C, Channon, K, Chapman, K, Charalambou, A, Chaudhuri, N, Checkley, A, Chen, J, Chetham, L, Chilvers, E R, Chinoy, H, Chong-James, K, Choudhury, N, Choudhury, G, Chowdhury, P, Chowienczyk, P, Christie, C, Clark, D, Clark, C, Clarke, J, Clift, P, Clohisey, S, Coburn, Z, Cole, J, Coleman, C, Connell, D, Connolly, B, Connor, L, Cook, A, Cooper, B, Coupland, C, Craig, T, Crisp, P, Cristiano, D, Crooks, M G, Cross, A, Cruz, I, Cullinan, P, Daines, L, Dalton, M, Dark, P, Dasgin, J, David, A, David, C, Davies, M, Davies, G, Davies, K, Davies, F, Davies, G A, Daynes, E, De Silva, T, De Soyza, A, Deakin, B, Deans, A, Defres, S, Dell, A, Dempsey, K, Dennis, J, Dewar, A, Dharmagunawardena, R, Diar Bakerly, N, Dipper, A, Diver, S, Diwanji, S N, Dixon, M, Djukanovic, R, Dobson, H, Dobson, C, Dobson, S L, Docherty, A B, Donaldson, A, Dong, T, Dormand, N, Dougherty, A, Dowling, R, Drain, S, Dulawan, P, Dunleavy, A, Dunn, S, Easom, N, Echevarria, C, Edwards, S, Edwardson, C, Elliott, B, Elliott, A, Ellis, Y, Elmer, A, Elneima, O, Evans, R A, Evans, J, Evans, H, Evans, D, Evans, R I, Evans, R, Evans, T, Fabbri, L, Fairbairn, S, Fairman, A, Fallon, K, Faluyi, D, Favager, C, Felton, T, Finch, J, Finney, S, Fisher, H, Fletcher, S, Flockton, R, Foote, D, Ford, A, Forton, D, Francis, R, Francis, S, Francis, C, Frankel, A, Fraser, E, Free, R, French, N, Fuld, J, Furniss, J, Garner, L, Gautam, N, Geddes, J R, George, P M, George, J, Gibbons, M, Gilmour, L, Gleeson, F, Glossop, J, Glover, S, Goodman, N, Gooptu, B, Gorsuch, T, Gourlay, E, Greenhaff, P, Greenhalf, W, Greenhalgh, A, Greening, N J, Greenwood, J, Greenwood, S, Gregory, R, Grieve, D, Gummadi, M, Gupta, A, Gurram, S, Guthrie, E, Hadley, K, Haggar, A, Hainey, K, Haldar, P, Hall, I, Hall, L, Halling-Brown, M, Hamil, R, Hanley, N A, Hardwick, H E, Hardy, E, Hargadon, B, Harrington, K, Harris, V, Harrison, E M, Harrison, P, Hart, N, Harvey, A, Harvey, M, Harvie, M, Havinden-Williams, M, Hawkes, J, Hawkings, N, Haworth, J, Hayday, A, Heaney, L G, Heeney, J L, Heightman, M, Heller, S, Henderson, M, Hesselden, L, Hillman, T, Hingorani, A, Hiwot, T, Ho, L P, Hoare, A, Hoare, M, Hogarth, P, Holbourn, A, Holdsworth, L, Holgate, D, Holmes, K, Holroyd-Hind, B, Horsley, A, Hosseini, A, Hotopf, M, Houchen, L, Howard, L, Howell, A, Hufton, E, Hughes, A, Hughes, J, Hughes, R, Humphries, A, Huneke, N, Hurst, J R, Hurst, R, Husain, M, Hussell, T, Ibrahim, W, Ient, A, Ingram, L, Ismail, K, Jackson, T, Jacob, J, James, W Y, Janes, S, Jarvis, H, Jayaraman, B, Jenkins, R G, Jezzard, P, Jiwa, K, Johnson, S, Johnson, C, Johnston, D, Jolley, C, Jolley, C J, Jones, I, Jones, S, Jones, D, Jones, H, Jones, G, Jones, M, Jose, S, Kabir, T, Kaltsakas, G, Kamwa, V, Kar, P, Kausar, Z, Kelly, S, Kerr, S, Key, A L, Khan, F, Khunti, K, King, C, King, B, Kitterick, P, Klenerman, P, Knibbs, L, Knight, S, Knighton, A, Kon, O M, Kon, S, Kon, S S, Korszun, A, Kotanidis, C, Koychev, I, Kurupati, P, Kwan, J, Laing, C, Lamlum, H, Landers, G, Langenberg, C, Lasserson, D, Lawrie, A, Lea, A, Leavy, O C, Lee, D, Lee, E, Leitch, K, Lenagh, R, Lewis, K, Lewis, V, Lewis, K E, Lewis, J, Lewis-Burke, N, Light, T, Lightstone, L, Lim, L, Linford, S, Lingford-Hughes, A, Lipman, M, Liyanage, K, Lloyd, A, Logan, S, Lomas, D, Lone, N I, Loosley, R, Lord, J M, Lota, H, Lucey, A, MacGowan, G, Macharia, I, Mackay, C, Macliver, L, Madathil, S, Madzamba, G, Magee, N, Mairs, N, Majeed, N, Major, E, Malim, M, Mallison, G, Man, W, Mandal, S, Mangion, K, Mansoori, P, Marciniak, S, Mariveles, M, Marks, M, Marshall, B, Martineau, A, Maskell, N, Matila, D, Matthews, L, Mayet, J, McAdoo, S, McAllister-Williams, H, McArdle, P, McArdle, A, McAulay, D, McAuley, H J C, McAuley, D F, McCafferty, K, McCann, G P, McCauley, H, McCourt, P, Mcgarvey, L, McGinness, J, McGovern, A, McGuinness, H, McInnes, I B, McIvor, K, McIvor, E, McMahon, A, McMahon, M J, McMorrow, L, Mcnally, T, McNarry, M, McQueen, A, McShane, H, Megson, S, Meiring, J, Menzies, D, Michael, A, Michael, B D, Milligan, L, Mills, N, Mitchell, J, Mohamed, A, Molyneaux, P L, Monteiro, W, Morley, A, Morrison, L, Morriss, R, Morrow, A, Moss, A, Moss, A J, Moss, P, Mukaetova-Ladinska, E, Munawar, U, Murali, E, Murira, J, Nassa, H, Neill, P, Neubauer, S, Newby, D, Newell, H, Newton Cox, A, Nicholson, T, Nicoll, D, Nolan, C M, Noonan, M J, Novotny, P, Nunag, J, Nyaboko, J, O'Brien, L, Odell, N, Ogg, G, Olaosebikan, O, Oliver, C, Omar, Z, Openshaw, P J M, Osbourne, R, Ostermann, M, Overton, C, Oxton, J, Pacpaco, E, Paddick, S, Papineni, P, Paradowski, K, Pareek, M, Parekh, D, Parfrey, H, Pariante, C, Parker, S, Parkes, M, Parmar, J, Parvin, R, Patale, S, Patel, B, Patel, S, Patel, M, Pathmanathan, B, Pavlides, M, Pearl, J E, Peckham, D, Pendlebury, J, Peng, Y, Pennington, C, Peralta, I, Perkins, E, Peto, T, Petousi, N, Petrie, J, Pfeffer, P, Phipps, J, Pimm, J, Piper Hanley, K, Pius, R, Plein, S, Plekhanova, T, Poinasamy, K, Polgar, O, Poll, L, Porter, J C, Portukhay, S, Powell, N, Price, L, Price, D, Price, A, Price, C, Prickett, A, Quaid, S, Quigley, J, Quint, J, Qureshi, H, Rahman, N, Rahman, M, Ralser, M, Raman, B, Ramos, A, Rangeley, J, Rees, T, Regan, K, Richards, A, Richardson, M, Rivera-Ortega, P, Robertson, E, Rodgers, J, Ross, G, Rossdale, J, Rostron, A, Routen, A, Rowland, A, Rowland, M J, Rowland, J, Rowland-Jones, S L, Roy, K, Rudan, I, Russell, R, Russell, E, Sabit, R, Sage, E K, Samani, N, Samuel, R, Sapey, E, Saralaya, D, Saratzis, A, Sargeant, J, Sass, T, Sattar, N, Saunders, K, Saunders, R, Saxon, W, Sayer, A, Schwaeble, W, Scott, J, Scott, K, Selby, N, Semple, M G, Sereno, M, Shah, K, Shah, A, Shah, P, Sharma, M, Sharpe, M, Sharpe, C, Shaw, V, Sheikh, A, Shevket, K, Shikotra, A, Short, J, Siddiqui, S, Sigfrid, L, Simons, G, Simpson, J, Singapuri, A, Singh, S J, Singh, C, Singh, S, Skeemer, J, Smith, I, Smith, J, Smith, L, Smith, A, Soares, M, Southern, D, Spears, M, Spencer, L G, Speranza, F, Stadon, L, Stanel, S, Steiner, M, Stensel, D, Stern, M, Stewart, I, Stockley, J, Stone, R, Storrie, A, Storton, K, Stringer, E, Subbe, C, Sudlow, C, Suleiman, Z, Summers, C, Summersgill, C, Sutherland, D, Sykes, D L, Sykes, R, Talbot, N, Tan, A L, Taylor, C, Taylor, A, Te, A, Tedd, H, Tee, C J, Tench, H, Terry, S, Thackray-Nocera, S, Thaivalappil, F, Thickett, D, Thomas, D, Thomas, D C, Thomas, A K, Thompson, A A R, Thompson, T, Thornton, T, Thwaites, R S, Tobin, M, Toingson, G F, Tong, C, Toshner, M, Touyz, R, Tripp, K A, Tunnicliffe, E, Turner, E, Turtle, L, Turton, H, Ugwuoke, R, Upthegrove, R, Valabhji, J, Vellore, K, Wade, E, Wain, L V, Wajero, L O, Walder, S, Walker, S, Wall, E, Wallis, T, Walmsley, S, Walsh, S, Walsh, J A, Watson, L, Watson, J, Watson, E, Welch, C, Welch, H, Welsh, B, Wessely, S, West, S, Wheeler, H, Whitehead, V, Whitney, J, Whittaker, S, Whittam, B, Wild, J, Wilkins, M, Wilkinson, D, Williams, N, Williams, B, Williams, J, Williams-Howard, S A, Willicombe, M, Willis, G, Wilson, D, Wilson, I, Window, N, Witham, M, Wolf-Roberts, R, Woodhead, F, Woods, J, Wootton, D, Worsley, J, Wraith, D, Wright, L, Wright, C, Wright, S, Xie, C, Yasmin, S, Yates, T, Yip, K P, Young, B, Young, S, Young, A, Yousuf, A J, Yousuf, A, Zawia, A, Zhao, B, Zongo, O, Evans, Rachael A, McAuley, Hamish J C, Harrison, Ewen M, Shikotra, Aarti, Singapuri, Amisha, Sereno, Marco, Elneima, Omer, Docherty, Annemarie B, Lone, Nazir I, Leavy, Olivia C, Daines, Luke, Baillie, J Kenneth, Brown, Jeremy S, Chalder, Trudie, De Soyza, Anthony, Diar Bakerly, Nawar, Easom, Nicholas, Geddes, John R, Greening, Neil J, Hart, Nick, Heaney, Liam G, Heller, Simon, Howard, Luke, Hurst, John R, Jacob, Joseph, Jenkins, R Gisli, Jolley, Caroline, Kerr, Steven, Kon, Onn M, Lewis, Keir, Lord, Janet M, McCann, Gerry P, Neubauer, Stefan, Openshaw, Peter J M, Parekh, Dhruv, Pfeffer, Paul, Rahman, Najib M, Raman, Betty, Richardson, Matthew, Rowland, Matthew, Semple, Malcolm G, Shah, Ajay M, Singh, Sally J, Sheikh, Aziz, Thomas, David, Toshner, Mark, Chalmers, James D, Ho, Ling-Pei, Horsley, Alex, Marks, Michael, Poinasamy, Krisnah, Wain, Louise V, and Brightling, Christopher E

Published
2021
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30. SIMON: Open-Source Knowledge Discovery Platform

Author

Tomic, Adriana, Tomic, Ivan, Waldron, Levi, Geistlinger, Ludwig, Kuhn, Max, Spreng, Rachel L., Dahora, Lindsay C., Seaton, Kelly E., Tomaras, Georgia, Hill, Jennifer, Duggal, Niharika A., Pollock, Ross D., Lazarus, Norman R., Harridge, Stephen D.R., Lord, Janet M., Khatri, Purvesh, Pollard, Andrew J., and Davis, Mark M.

Published
2021
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31. The impact of trauma relevant concentrations of prostaglandin E2 on the anti-microbial activity of the innate immune system.

Author

Nicholson, Thomas, Belli, Antonio, Lord, Janet M., and Hazeldine, Jon

Subjects
MONONUCLEAR leukocytes, NATURAL immunity, PROTEIN kinase inhibitors, THERAPEUTICS, PHAGOCYTOSIS
Abstract

Background: The mechanisms underlying the state of systemic immune suppression that develops following major trauma are poorly understood. A post-injury increase in circulating levels of prostaglandin E2 (PGE2) has been proposed as a contributory factor, yet few studies have addressed how trauma influences PGE2 biology. Methods: Blood samples from 95 traumatically-injured patients (injury severity score ≥8) were collected across the pre-hospital (≤2 hours), acute (4-12 hours) and subacute (48-72 hours) post-injury settings. Alongside ex vivo assessments of lipopolysaccharide (LPS)-induced cytokine production by monocytes, neutrophil reactive oxygen species production and phagocytosis, serum concentrations of PGE2 and its scavenger albumin were measured, and the expression of enzymes and receptors involved in PGE2 synthesis and signalling analysed. Leukocytes from trauma patients were treated with cyclooxygenase (COX) inhibitors (indomethacin or NS-398), or the protein kinase A inhibitor H89, to determine whether injury-induced immune suppression could be reversed by targeting the PGE2 pathway. The effect that trauma relevant concentrations of PGE2 had on the anti-microbial functions of neutrophils, monocytes and monocyte-derived macrophages (MDMs) from healthy controls (HC) was examined, as was the effect of PGE2 on efferocytosis. To identify factors that may trigger PGE2 production post-trauma, leukocytes from HC were treated with mitochondrial-derived damage associated molecular patterns (mtDAMPs) and COX-2 expression and PGE2 generation measured. Results: PGE2 concentrations peaked in blood samples acquired ≤2 hours post-injury and coincided with significantly reduced levels of albumin and impaired LPS-induced cytokine production by monocytes. Significantly higher COX-2 and phospholipase A2 expression was detected in neutrophils and/or peripheral blood mononuclear cells isolated from trauma patients. Treatment of patient leukocytes with indomethacin, NS-398 or H89 enhanced LPS-induced cytokine production and neutrophil extracellular trap generation. Exposure to physiological concentrations of PGE2 suppressed the anti-microbial activity of monocytes, neutrophils and MDMs of HC, but did not influence efferocytosis. In a formyl-peptide receptor-1 dependent manner, mtDAMP treatment significantly increased COX-2 protein expression in neutrophils and monocytes, which resulted in increased PGE2 production. Conclusions: Physiological concentrations of PGE2 suppress the anti-microbial activities of neutrophils, monocytes and MDMs. Targeting the PGE2 pathway could be a therapeutic approach by which to enhance innate immune function post-injury. [ABSTRACT FROM AUTHOR]

Published
2024
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37. 1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study.

Author

Leavy, Olivia C, Russell, Richard J, Harrison, Ewen M, Lone, Nazir I, Kerr, Steven, Docherty, Annemarie B, Sheikh, Aziz, Richardson, Matthew, Elneima, Omer, Greening, Neil J, Harris, Victoria Claire, Houchen-Wolloff, Linzy, McAuley, Hamish J C, Saunders, Ruth M, Sereno, Marco, Shikotra, Aarti, Singapuri, Amisha, Aul, Raminder, Beirne, Paul, Bolton, Charlotte E, Brown, Jeremy S, Choudhury, Gourab, Diar Bakerly, Nawar, Easom, Nicholas, Echevarria, Carlos, Fuld, Jonathan, Hart, Nick, Hurst, John R, Jones, Mark, Parekh, Dhruv, Pfeffer, Paul, Rahman, Najib M, Rowland-Jones, Sarah, Shah, Ajay M, Wootton, Dan G, Jolley, Caroline, Thompson, A A Roger, Chalder, Trudie, Davies, Melanie J, De Soyza, Anthony, Geddes, John R, Greenhalf, William, Heller, Simon, Howard, Luke, Jacob, Joseph, Jenkins, R Gisli, Lord, Janet M, Man, Will D-C, McCann, Gerry P, Neubauer, Stefan, Openshaw, Peter J M, Porter, Joanna, Rowland, Matthew J, Scott, Janet T, Semple, Malcolm G, Singh, Sally J, Thomas, David, Toshner, Mark, Lewis, Keir, Heaney, Liam G, Briggs, Andrew, Zheng, Bang, Thorpe, Mathew, Quint, Jennifer K, Chalmers, James D, Ho, Ling-Pei, Horsley, Alex, Marks, Michael, Poinasamy, Krisnah, Raman, Betty, Wain, Louise V, Brightling, Christopher E, Evans, Rachael A, Leavy, Olivia C, Russell, Richard J, Harrison, Ewen M, Lone, Nazir I, Kerr, Steven, Docherty, Annemarie B, Sheikh, Aziz, Richardson, Matthew, Elneima, Omer, Greening, Neil J, Harris, Victoria Claire, Houchen-Wolloff, Linzy, McAuley, Hamish J C, Saunders, Ruth M, Sereno, Marco, Shikotra, Aarti, Singapuri, Amisha, Aul, Raminder, Beirne, Paul, Bolton, Charlotte E, Brown, Jeremy S, Choudhury, Gourab, Diar Bakerly, Nawar, Easom, Nicholas, Echevarria, Carlos, Fuld, Jonathan, Hart, Nick, Hurst, John R, Jones, Mark, Parekh, Dhruv, Pfeffer, Paul, Rahman, Najib M, Rowland-Jones, Sarah, Shah, Ajay M, Wootton, Dan G, Jolley, Caroline, Thompson, A A Roger, Chalder, Trudie, Davies, Melanie J, De Soyza, Anthony, Geddes, John R, Greenhalf, William, Heller, Simon, Howard, Luke, Jacob, Joseph, Jenkins, R Gisli, Lord, Janet M, Man, Will D-C, McCann, Gerry P, Neubauer, Stefan, Openshaw, Peter J M, Porter, Joanna, Rowland, Matthew J, Scott, Janet T, Semple, Malcolm G, Singh, Sally J, Thomas, David, Toshner, Mark, Lewis, Keir, Heaney, Liam G, Briggs, Andrew, Zheng, Bang, Thorpe, Mathew, Quint, Jennifer K, Chalmers, James D, Ho, Ling-Pei, Horsley, Alex, Marks, Michael, Poinasamy, Krisnah, Raman, Betty, Wain, Louise V, Brightling, Christopher E, and Evans, Rachael A

Abstract

In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.

Published
2024

42. Duke Activity Status Index and Liver Frailty Index predict mortality in ambulatory patients with advanced chronic liver disease: A prospective, observational study

Author

Williams, Felicity R., primary, Quinlan, Jonathan, additional, Freer, Alice, additional, Morrison, Breanna, additional, Sitch, Alice, additional, Hockey, Florence, additional, Klas, Natasza, additional, Towey, Jennifer, additional, Perera, Thamara P. R., additional, Rajoriya, Neil, additional, Lord, Janet M., additional, and Armstrong, Matthew J., additional

Published
2024
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45. DYNamic Assessment of Multi‐Organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19.

Author

Gupta, Ayushman, Nicholas, Rosemary, McGing, Jordan J., Nixon, Aline V., Mallinson, Joanne E., McKeever, Tricia M., Bradley, Christopher R., Piasecki, Mathew, Cox, Eleanor F., Bonnington, James, Lord, Janet M., Brightling, Christopher E., Evans, Rachael A., Hall, Ian P., Francis, Susan T., Greenhaff, Paul L., and Bolton, Charlotte E.

Subjects
NUCLEAR magnetic resonance spectroscopy, MAGNETIC resonance imaging, MOTOR unit, LEG muscles, INSULIN resistance
Abstract

We evaluated the impacts of COVID‐19 on multi‐organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5–7 months post‐discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole‐body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual‐energy X‐ray absorptiometry, short physical performance battery (SPPB), intra‐muscular electromyography, quadriceps strength and fatigability, and daily step‐count. There was a greater insulin response (incremental area under the curve, median (inter‐quartile range)) during the OGTT in patients [18,289 (12,497–27,448) mIU/min/L] versus controls [8655 (7948–11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post‐prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole‐body/regional adiposity, but step‐count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force‐loss, motor unit properties and post‐exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross‐sectional study, individuals without known previous morbidity who survived severe COVID‐19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery. What is the central question of the study?What are the post‐COVID‐19 symptoms and associated metabolic and physiological sequelae in patients who contracted acute severe infection compared to healthy control volunteers?What is the main finding and its importance?Patients 5–7 months after hospital discharge for acute severe COVID‐19 compared to healthy control volunteers had (i) an increased insulin response to an oral glucose challenge, without demonstrating different whole‐body fuel oxidation rates, and (ii) greater perception of fatigue and worse functional mobility, though no abnormalities in muscle, heart or brain structure and function were identified. This provides novel targets for rehabilitation strategies in individuals recovering after severe COVID‐19. [ABSTRACT FROM AUTHOR]

Published
2024
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