Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study
Rachael A Evans, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish McAuley, A Shikotra, Amisha Singapuri, Marco Sereno, Ruth Saunders, Victoria Harris, Linzy Houchen‐Wolloff, Raminder Aul, Paul Beirne, Charlotte E. Bolton, Jeremy Brown, Gourab Choudhury, N Diar-Bakerly, Nicholas Easom, Carlos Echevarria, Jonathan Fuld, Nicholas Hart, John R. Hurst, Mark G. Jones, Dhruv Parekh, Paul Pfeffer, Najib M. Rahman, Sarah Rowland‐Jones, Aarti Shah, Dan Wootton, Trudie Chalder, Matthew Davies, Anthony De Soyza, J R Geddes, William Greenhalf, Neil Greening, Liam G. Heaney, Simon Heller, Luke Howard, Joseph Jacob, Gísli Jenkins, Janet M. Lord, William D‐C Man, Gerry P McCann, Stefan Neubauer, Peter Openshaw, Joanna C. Porter, Matthew Rowland, J. T. Scott, Malcolm G. Semple, Sally Singh, David Thomas, Mark Toshner, Keir Lewis, Ryan S. Thwaites, Andrew Briggs, Annemarie B Docherty, S Kerr, Nazir Lone, Jennifer K Quint, Aziz Sheikh, Mathew Thorpe, Bang Zheng, James D. Chalmers, Ling‐Pei Ho, Alex Horsley, Michael Marks, K Poinasamy, Betty Raman, Ewen M. Harrison, Louise V. Wain, Christopher E. Brightling, Kathryn M. Abel, Huzaifa Adamali, Davies Adeloye, O Adeyemi, R Adrego, L A Aguilar Jimenez, Shazaad Ahmad, Nafees Haider, Rizwan Ahmed, N Ahwireng, Mark Ainsworth, B Al-Sheklly, A Alamoudi, Mohammad Ali, M Aljaroof, AM All, Louise Allan, R Allen, L. Allerton, Lynne Allsop, P. Almeida, Doris Altmann, Maria Alvarez Corral, S Amoils, Debra Anderson, Chrystalina A. Antoniades, G Arbane, A. Arias, Chérie Armour, Lará Armstrong, Natalie Armstrong, David Arnold, H Arnold, Abdul Ashish, Andrew Ashworth, Mark Ashworth, S Aslani, H Assefa-Kebede, Catherine Atkin, Philip A. Atkin, Htin Aung, Luke Austin, Cristina Avram, A Ayoub, Marta Babores, Rob Baggott, J. Bagshaw, David Baguley, L. Charles Bailey, J. Kenneth Baillie, S. Bain, M Bakali, M Bakau, Eileen Baldry, David Baldwin, Clive Ballard, Amitava Banerjee, B. 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Abstract
BACKGROUND: No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. FINDINGS: 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7-9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46-0·99]), obesity (0·50 [0·34-0·74]) and invasive mechanical ventilation (0·42 [0·23-0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74-1·00]), at 5 months (0·74 [0·64-0·88]) to 1 year (0·75 [0·62-0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. INTERPRETATION: The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. FUNDING: UK Research and Innovation and National Institute for Health Research.
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