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

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Abstract

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.

Original languageEnglish
Pages (from-to)673-684
Number of pages12
JournalThe Lancet Respiratory Medicine
Volume11
Issue number8
Early online date15 Apr 2023
DOIs
Publication statusPublished online - 15 Apr 2023

Bibliographical note

Funding Information:
CJ is funded by an Engineering and Physical Sciences Research Council (EPSRC) Mathematics Doctoral Training Partnership (EP/W523884/1). L-PH is supported in part by the Oxford NIHR Biomedical Research Centre. PLM is supported by an Action for Pulmonary Fibrosis Mike Bray Fellowship and an Asthma + Lung UK Chair in Respiratory Research. KP-H receives funding from Innovate UK (TS/T013028/1) and the UK Medical Research Council (MRC; MR/W006111/1). JCP receives funding from the NIHR University College London Hospitals Biomedical research centre and Breathing Matters charity. BR is funded by the British Heart Foundation Oxford Centre of Research Excellence (RE/18/3/34214). ABD is funded by a Wellcome fellowship (216606/Z/19/Z). AART is supported by a British Heart Foundation intermediate clinical fellowship (FS/18/13/33281). LVW is supported by the GlaxoSmithKline/Asthma + Lung UK Chair in Respiratory Research (C17-1). DGW is funded by an NIHR Advanced Fellowship (NIHR300669). RGJ is supported by a NIHR Research Professorship (RP-2017-08-ST2-014). JFB and PSC are supported by an MRC transition support fellowship (MR/T032529/1). IDS is supported by a fellowship funded by The Rayne Foundation. The work was also supported by an Asthma + Lung UK Malcolm Walleans Grant. This work was supported by the NIHR Manchester Biomedical Research Centre (grant number NIHR203308; JFB, MKR, and AH). The study was also funded by UK Research and Innovation and National Institute of Health Research (grant references: EP/V051490/1, MR/V027859/1, MR/W006111/1, and COV0319). PHOSP-COVID is jointly funded by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19 grant references above. The views expressed in the publication are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health and Social Care. This study would not be possible without all the participants who gave 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 the 65 NHS trusts and health boards and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, the Health Research Authority, the 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. This research was done with the UK Biobank Resource under application number 6818. We thank the participants and researchers from the UK Biobank who contributed or collected data. We thank Kate Holmes at the NIHR Office for Clinical Research Infrastructure (NOCRI) for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well the NIHR Office for Clinical Research Infrastructure (NOCRI) for coordinating this work. We are grateful to all the charities that provided insights for this study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma + Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations, and Versus Arthritis. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group and Long Covid Support. We also thank the reviewers whose thoughtful comments improved the quality of the Article.

Funding Information:
CJ is funded by an Engineering and Physical Sciences Research Council (EPSRC) Mathematics Doctoral Training Partnership (EP/W523884/1). L-PH is supported in part by the Oxford NIHR Biomedical Research Centre. PLM is supported by an Action for Pulmonary Fibrosis Mike Bray Fellowship and an Asthma + Lung UK Chair in Respiratory Research. KP-H receives funding from Innovate UK (TS/T013028/1) and the UK Medical Research Council (MRC; MR/W006111/1). JCP receives funding from the NIHR University College London Hospitals Biomedical research centre and Breathing Matters charity. BR is funded by the British Heart Foundation Oxford Centre of Research Excellence (RE/18/3/34214). ABD is funded by a Wellcome fellowship (216606/Z/19/Z). AART is supported by a British Heart Foundation intermediate clinical fellowship (FS/18/13/33281). LVW is supported by the GlaxoSmithKline/Asthma + Lung UK Chair in Respiratory Research (C17-1). DGW is funded by an NIHR Advanced Fellowship (NIHR300669). RGJ is supported by a NIHR Research Professorship (RP-2017-08-ST2-014). JFB and PSC are supported by an MRC transition support fellowship (MR/T032529/1). IDS is supported by a fellowship funded by The Rayne Foundation. The work was also supported by an Asthma + Lung UK Malcolm Walleans Grant. This work was supported by the NIHR Manchester Biomedical Research Centre (grant number NIHR203308; JFB, MKR, and AH). The study was also funded by UK Research and Innovation and National Institute of Health Research (grant references: EP/V051490/1, MR/V027859/1, MR/W006111/1, and COV0319). PHOSP-COVID is jointly funded by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19 grant references above. The views expressed in the publication are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR, or the Department of Health and Social Care. This study would not be possible without all the participants who gave 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 the 65 NHS trusts and health boards and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, the Health Research Authority, the 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. This research was done with the UK Biobank Resource under application number 6818. We thank the participants and researchers from the UK Biobank who contributed or collected data. We thank Kate Holmes at the NIHR Office for Clinical Research Infrastructure (NOCRI) for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well the NIHR Office for Clinical Research Infrastructure (NOCRI) for coordinating this work. We are grateful to all the charities that provided insights for this study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma + Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations, and Versus Arthritis. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group and Long Covid Support. We also thank the reviewers whose thoughtful comments improved the quality of the Article.

Publisher Copyright:
© 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Keywords

  • COVID-19/complications
  • Hospitalization
  • Hospitals
  • Humans
  • Lung
  • Prospective Studies
  • Sleep Wake Disorders/epidemiology
  • Sleep/physiology
  • United Kingdom/epidemiology

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