April 15, 2023

A study published in the Lancet Respiratory Medicine and presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) looks at sleep disturbance, dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK.

Dr Ivana Rosenzweig, Clinical Reader in the Neuroscience of Sleep, Kings College London, said:

Does the press release accurately reflect the science?

The study is a well-designed prospective multicentre cohort substudy that investigated the effects of sleep disturbance on recovery after COVID-19 in a cohort of adult participants, who were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Based on their findings, the authors of the study (justifiably) speculate, that sleep disruption may be a major drive of breathlessness in these patients. However, it remains unclear to which extent this is further affected/moderated by the associated reduced muscle function and increased anxiety, both also recognised causes of breathlessness.

Is this good quality research? Are the conclusions backed up by solid data?

I agree that major strengths of the study include its size, multicentre nature, and the use of different complementary assessment measures to evaluate sleep disturbance. The findings and the authors conclusions are also further supported by the replicated and consistent clinical associations across each evaluation method.

Have the authors accounted for confounders? Are there important limitations to be aware of?

This is a substudy of a larger study, and thus, it is impossible to exclude that there are other potentially unaccounted for confounders. However, the authors were frank that only associations and learned conclusions can be done in clinical research, this is sometimes as good, and as close as we can get in uncovering the underlying mechanisms, and the authors have done their best to declare all possible limitations and to exclude or account for all known confounders.

What are the implications in the real world? Is there any overspeculation?

It will be now really interesting to see if interventions targeting sleep disturbance can improve daytime breathlessness too.

Dr Richard Russell, Clinical Reader in Respiratory Medicine at King College London, said:

This is an important study in that it sheds light into the nature of Long-Covid, its impact on those living with it and also a new focus for treatment. This nation-wide study was performed by an expert group who have looked at Long-Covid in a robust manner. This study has generated new evidence on this condition and also confirmed the importance of sleep to human well-being.

Sleep quality is not just about quantity; too little is not good for health as is too much. Quality is important. The finding that sleep disturbance occurs in people living with Long-Covid and that this is linked to symptoms is important as there are effective strategies to improve sleep quality that will hopefully impact the burden of this disease and improve the lives of those living with it.

Prof David Ray, Professor of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Diabetes; and Sir Jules Thorn Sleep and Circadian Neuroscience Institute, University of Oxford, said:

This is an observational cohort study. People hospitalised with Covid, after discharge were invited to take part, and about 50% of those approached did so. Observational data can identify associations, and here breathlessness was associated with poor sleep. It could be that breathlessness leads to poor sleep, the other way around, or something else e.g. anxiety could lead to both. The authors acknowledge the limitations of the study design, and attempt to control for them. However, it is clear that poor sleep and poor quality of life are closely linked, and so attention to improving sleep may be a low risk, and high gain approach to help people suffering with long covid. That would require a proper interventional trial, and that may be hard to do as the covid waves are now subsiding.

Prof Nicholas Hart, Professor of Respiratory and Critical Care Medicine, Kings College London, said:

This important study provides further insights into physical and mental health impact following hospitalisation as a consequence of COVID-19 infection. This study has shown that sleep disturbance, anxiety and dyspnoea (breathlessness) were more prevalent in hospitalised COVID-19 survivors following discharge. Of particular interest, these patients showed greater rest time and less efficient sleep during recovery. The next step is to confirm or exclude sleep disordered breathing or other sleep disorders, such as periodic limb movement disorder, so that we can apply interventions to improve sleep quality and assess the impact on breathlessness and anxiety.

Dr Julie Darbyshire, Senior Researcher, University of Oxford, said:

Patients rarely sleep well in hospital and poor sleep following hospital admission is common. Feeling breathless, especially overnight, is distressing and this study demonstrates how this is associated with disturbed sleep.

This study assessed sleep using validated methods which ensures quality of recording and comparison with other similar sleep assessment studies.

It is important to note that this study asked people to recall their sleep before they were hospitalised which is an unreliable measure. Comparisons between sleep before and after hospitalisation are therefore less reliable than comparisons between measures reported in real-time. This should not detract from the wider message that sleep quality after hospitalisation with COVID-19 is poor and is also associated with lower measures of health.

The statistical analysis in the article provides compelling evidence for the association between sleep and breathlessness, muscle weakness, and anxiety after hospitalisation for COVID-19. The press release suggests that sleep disruption might cause breathlessness (dyspnoea) whereas the article itself reports an association between the two without attributing a causal pathway. The press release does not mention the other primary associations with greatest sleep irregularity which include a lower deprivation index, smoking, existing depression or anxiety, diabetes, high blood pressure, and kidney disease.

Although we cant be sure from this study, it is plausible that targeting sleep disruption following admission to hospital for Covid may improve general health and recovery in some people, including muscle strength, anxiety, and breathlessness. In general I would say that for any patient struggling to sleep, regardless of why they were admitted to hospital, addressing this is likely to have an effect on their recovery.

Prof Amitava Banerjee, Professor of Clinical Data Science and Honorary Consultant Cardiologist, Institute of Health Informatics, UCL, said:

This is a detailed and very interesting analysis using novel methods, showing that sleep disturbance is common in patients hospitalised with COVID, even 5-8 months following hospital admission, and the sleep quality seems to be worse, even when compared with control groups in UK Biobank, both hospitalised and non-hospitalised. The authors found associations with multiple symptoms, especially shortness of breath, anxiety and muscle weakness.

However, there are some limitations. First, as the accompanying editorial notes, there may be biases in the patients who had sleep monitoring, compared to the overall population of people hospitalised with Covid. Second, this study only concerns hospitalised post- Covid individuals. The majority of people with Long Covid were not hospitalised for Covid so the results may not be generalisable to this larger group. Third, this study only shows correlation and does not show that sleep disturbance causes the symptoms of long Covid. For example, the sleep disturbances could well be an effect rather than a cause of symptoms like breathlessness and anxiety.

Good quality sleep is important for health and reduces risk of chronic diseases, such that it is included in the American Heart Associations Lifes Essential 8 health behaviour recommendations (https://www.heart.org/en/healthy-living/healthy-lifestyle/lifes-essential-8). Quality of sleep is therefore likely to be important for those with Long Covid in reducing their risk of chronic disease, but the role of sleep in the mechanism of Long Covid needs further research.

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 by Callum Jackson et al. was published in the Lancet Respiratory Medicine at 23:30 UK time on Saturday 15 April 2023.

DOI: 10.1016/S2213-2600(23)00124-8

Declared interests

Dr Ivana Rosenzweig: No COIs.

Prof David Ray: No conflicts.

Prof Nicholas Hart: I am part of PHOSP but not part of this study. No other conflicts relating to this work.

Dr Julie Darbyshire: I have no conflicts of interest to declare. I was the Chief Investigator for the NIHR funded SILENCE study which investigated the relationship between sound levels, sleep, and delirium in the intensive care unit, and Im currently working alongside patients with long covid to understand how long covid clinics can best support their recovery.

Prof Amitava Banerjeeis the chief investigator of STIMULATE-ICP, an NIHR-funded study in non-hospitalised individuals with Long Covid. He has also received research funding from Astra Zeneca unrelated to Covid or Long Covid.

For all other experts, no reply to our request for DOIs was received.

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