Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Louise Sigfrid¹, Thomas M Drake², Ellen Pauley³, Edwin C Jesudason⁴, Piero Olliaro⁵, Wei Shen Lim⁶, Annelies Gillesen⁷, Colin Berry⁸, David J Lowe⁹, Joanne McPeake¹⁰, Nazir Lone¹¹, Daniel Munblit^{12

13}, Muge Cevik¹⁴, Anna Casey¹⁵, Peter Bannister¹⁵, Clark D Russell¹⁶, Lynsey Goodwin^{17

18}, Antonia Ho¹⁹, Lance Turtle^{20

21}, Margaret E O'Hara²², Claire Hastie²², Chloe Donohue²³, Rebecca G Spencer²⁴, Cara Donegan²⁴, Alison Gummery²⁴, Janet Harrison^{25

26}, Hayley E Hardwick^{26

27}, Claire E Hastie²⁸, Gail Carson²⁹, Laura Merson³⁰, J Kenneth Baillie³¹, Peter Openshaw³², Ewen M Harrison³³, Annemarie B Docherty^{34

35}, Malcolm G Semple^{36

37}, Janet T Scott³⁸; ISARIC4C investigators

Affiliations

¹ Clinical Research Fellow, Public Health Specialist, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
² Clinical Research Fellow, Centre for Medical Informatics, University of Edinburgh, Edinburgh, UK.
³ Medical Student, University of Edinburgh Medical School, Edinburgh, UK.
⁴ Consultant in Rehabilitation Medicine, NHS Lothian, Edinburgh, UK.
⁵ Professor of Poverty Related Infectious Diseases, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
⁶ Honorary Professor of Respiratory Medicine, Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
⁷ Senior Clinical Trial Nurse, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
⁸ Professor of Cardiology and Imaging, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
⁹ Consultant in Emergency Medicine, NHS Greater Glasgow and Clyde, Emergency Department, Glasgow, UK.
¹⁰ Nurse Consultant in Clinical Research, School of Medicine, Dentistry and Nursing, University of Glasgow, UK.
¹¹ Senior Clinical Lecturer in Critical Care, Usher Institute, University of Edinburgh, Edinburgh, UK.
¹² Professor of Paediatrics, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
¹³ Clinical Senior Lecturer, Inflammation, Repair and Development Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
¹⁴ Clinical Lecturer, Division of Infection and Global Health Research, University of St Andrews.
¹⁵ Medical Student, Brighton and Sussex Medical School, Brighton, UK.
¹⁶ Clinical Lecturer in Infectious Diseases, Centre for Inflammation Research, University of Edinburgh, UK.
¹⁷ Specialist Registrar in Infectious Diseases and General Internal Medicine, Tropical and Infectious Diseases Unit, North Manchester General Hospital, Delaunays Rd, Manchester, UK.
¹⁸ Clinical Research Fellow, National Institute of Health Research (NIHR) Health Protection Research Unit in emerging and zoonotic infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
¹⁹ Clinical Senior Lecturer/Consultant in Infectious Diseases, MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
²⁰ Senior Clinical Lecturer, NIHR Health Protection Research Unit in emerging and zoonotic infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
²¹ Consultant in Infectious Disease, Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
²² Patient-advocate, Long COVID Support, Birmingham, UK.
²³ Trials Coordinator, Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
²⁴ Project Administrator, Institute of Infection, Veterinary and Ecological Sciences (IVES), University of Liverpool, Liverpool, UK.
²⁵ Data Base Developer, National Institute of Health Research (NIHR) Health Protection research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
²⁶ Institute of Infection and Global Health, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
²⁷ Project Manager, National Institute of Health Research (NIHR) Health Protection research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
²⁸ Lecturer in Public Health, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
²⁹ Head, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
³⁰ Head of Data, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
³¹ Senior Clinical Research Fellow, Roslin Institute, University of Edinburgh, Edinburgh, UK.
³² Prof. of Experimental Medicine, National Heart and Lung Institute, Imperial College, London UK.
³³ Director Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
³⁴ Wellcome Clinical Research Career Development Fellow, Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
³⁵ Consultant in Intesnive Care Medicine, Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.
³⁶ Professor of Child Health and Outbreak Medicine, Health Protection Research Unit In Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK.
³⁷ Consultant in Respiratory Medicine, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK.
³⁸ Clinical Lecturer in Infectious Disease, MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.

PMID: 34386785
PMCID: PMC8343377
DOI: 10.1016/j.lanepe.2021.100186

Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Louise Sigfrid et al. Lancet Reg Health Eur. 2021 Sep.

. 2021 Sep:8:100186.

doi: 10.1016/j.lanepe.2021.100186. Epub 2021 Aug 6.

Authors

Affiliations

¹ Clinical Research Fellow, Public Health Specialist, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
² Clinical Research Fellow, Centre for Medical Informatics, University of Edinburgh, Edinburgh, UK.
³ Medical Student, University of Edinburgh Medical School, Edinburgh, UK.
⁴ Consultant in Rehabilitation Medicine, NHS Lothian, Edinburgh, UK.
⁵ Professor of Poverty Related Infectious Diseases, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
⁶ Honorary Professor of Respiratory Medicine, Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
⁷ Senior Clinical Trial Nurse, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
⁸ Professor of Cardiology and Imaging, Institute of Cardiovascular and Medical Sciences, University of Glasgow.
⁹ Consultant in Emergency Medicine, NHS Greater Glasgow and Clyde, Emergency Department, Glasgow, UK.
¹⁰ Nurse Consultant in Clinical Research, School of Medicine, Dentistry and Nursing, University of Glasgow, UK.
¹¹ Senior Clinical Lecturer in Critical Care, Usher Institute, University of Edinburgh, Edinburgh, UK.
¹² Professor of Paediatrics, Department of Paediatrics and Paediatric Infectious Diseases, Institute of Child's Health, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
¹³ Clinical Senior Lecturer, Inflammation, Repair and Development Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
¹⁴ Clinical Lecturer, Division of Infection and Global Health Research, University of St Andrews.
¹⁵ Medical Student, Brighton and Sussex Medical School, Brighton, UK.
¹⁶ Clinical Lecturer in Infectious Diseases, Centre for Inflammation Research, University of Edinburgh, UK.
¹⁷ Specialist Registrar in Infectious Diseases and General Internal Medicine, Tropical and Infectious Diseases Unit, North Manchester General Hospital, Delaunays Rd, Manchester, UK.
¹⁸ Clinical Research Fellow, National Institute of Health Research (NIHR) Health Protection Research Unit in emerging and zoonotic infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
¹⁹ Clinical Senior Lecturer/Consultant in Infectious Diseases, MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
²⁰ Senior Clinical Lecturer, NIHR Health Protection Research Unit in emerging and zoonotic infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
²¹ Consultant in Infectious Disease, Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
²² Patient-advocate, Long COVID Support, Birmingham, UK.
²³ Trials Coordinator, Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
²⁴ Project Administrator, Institute of Infection, Veterinary and Ecological Sciences (IVES), University of Liverpool, Liverpool, UK.
²⁵ Data Base Developer, National Institute of Health Research (NIHR) Health Protection research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
²⁶ Institute of Infection and Global Health, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
²⁷ Project Manager, National Institute of Health Research (NIHR) Health Protection research Unit in Emerging and Zoonotic Infections, Liverpool, UK.
²⁸ Lecturer in Public Health, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
²⁹ Head, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
³⁰ Head of Data, ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
³¹ Senior Clinical Research Fellow, Roslin Institute, University of Edinburgh, Edinburgh, UK.
³² Prof. of Experimental Medicine, National Heart and Lung Institute, Imperial College, London UK.
³³ Director Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
³⁴ Wellcome Clinical Research Career Development Fellow, Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.
³⁵ Consultant in Intesnive Care Medicine, Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.
³⁶ Professor of Child Health and Outbreak Medicine, Health Protection Research Unit In Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK.
³⁷ Consultant in Respiratory Medicine, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, UK.
³⁸ Clinical Lecturer in Infectious Disease, MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.

PMID: 34386785
PMCID: PMC8343377
DOI: 10.1016/j.lanepe.2021.100186

Abstract

Background: This study sought to establish the long-term effects of Covid-19 following hospitalisation.

Methods: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L).

Findings: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age.

Interpretation: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.

Funding: National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation.

Keywords: Covid-19; long-Covid; long-term outcomes; post-Covid; post-acute Covid-19; quality of life; sequelae.

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Conflict of interest statement

CRD declares funding from the Medical Research Council, UK. JM reports a University of Cambridge Research Fellowship. WSL reports unrestricted investigator-initiated research funding from Pfizer for an unrelated multi-centre study in pneumonia, in which WSL is the CI and UK NIHR research funding for unrelated clinical trials in the fields of COVID-19, tuberculosis and community-acquired pneumonia. WSL's role on the Joint Committee on Vaccination and Immunisation (JCVI), UK and chair of COVID-19 Immunisation and as National Lead on British Thoracic Society community acquired pneumonia audit programme is unpaid and unrelated to this work. CB declares a British Heart Foundation Centre award, and a project grants from the Chief Scientist Office, Scottish Government CSO Long Term Effects and from Heart Research UK unrelated to this work. LG declares support from Pfizer & Gilead for attendance at an educational meeting in Nov 2018 and April 2019, for cost of conference registration fee, accommodation and flights unrelated to this work. PJMO reports personal fees from consultancy, grants from MRC, EU, NIHR Biomedical Research Centres, MRC/GSK, Wellcome Trust, NIHR (HPRU) and NIHR Senior Investigator Award. Personal fees from European Respiratory Society, grants from MRC Global Challenge Research fund, other from Nestle Discussion Forum (unpaid), Pfizer antivirals advisory board (unpaid) outside of the submitted work and the role of President of the British Society for Immunology was an unpaid appointment but PJMO's travel and accommodation at some meetings is provided by the Society. MGS reports grants from the National Institute for Health Research (NIHR), Medical Research Council. NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. All other authors have no interests to declare.

Figures

Fig 1 — **Fig. 1**
Patient inclusion flowchart

Fig 2 — **Fig. 2**
Proportion of new or persistent symptoms occurring (Fig. 2A) and their co-occurrence with each other (Fig. 2B). For Figure 2A, fatigue is coloured in green as this outcome was derived from the fatigue visual analogue outcome, where a fatigue rating of 2 or greater was considered as the presence of the fatigue symptom (see Supplementary Table 7 for raw values). Erectile dysfunction affected 23·4% (45/192) of males included, not shown as Figure 2A presents data for any sex. For Figure 2B, the Jaccard similarity index was calculated and presented as intensity of red colour, with 0 (white) being no co-occurrence and 1 (bright red) being always co-occurring.

Fig 3 — **Fig. 3**
Outcomes stratified by age and presence of one or more comorbidities. Figure 3A – Proportion of participants not feeling fully recovered; Figure 3B – Proportion of participants with new or persistent symptoms; Figure 3C - Proportion of participants with increased breathlessness as measured by MRC dyspnoea scale; Figure 3D – Participant rated fatigue on 0 to 10 VAS; Figure 3E – Change in overall EQ5D-5L summary health index; Figure 3F – presence of new or worse disability in at least one Washington Group disability domain. Point estimates presented alongside 95% confidence intervals. MRC – Medical Research Council, VAS – Visual Analogue Scale.

Fig 4 — **Fig. 4**
MRC Dyspnoea scale prior to Covid-19 onset and at the time of follow-up. Figure 4A – MRC dyspnoea scale reported prior to onset of Covid-19 symptoms; Figure 4B – MRC dyspnoea scale at the time of follow-up; Figure 4C – Alluvial plot of proportion of the changes in proportion of males and females in each MRC scale grade before symptom onset and at time of follow-up, stratified in each sex group by admission to critical care. In Figure 4C, for females, there are greater numbers of participants who begin at MRC 1 and transition to higher levels on the scale compared with males. MRC – Medical Research Council

Fig 5 — **Fig. 5**
Multilevel model for primary outcome of self-reported recovery (reference level is feeling fully recovered)

See this image and copyright information in PMC

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Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Affiliations

Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical

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