Chris Rachael Louise

Study reveals seven in ten patients hospitalised with COVID-19 not fully recovered five months post-discharge

Updated: March 24, 2021, 11:57 a.m.

Access the full pre-print here: https://www.medrxiv.org/content/10.1101/2021.03.22.21254057v1

  • Majority of patients hospitalised with COVID-19 have not fully recovered after five months
  • Those who experience more persistent symptoms tend to be middle-aged, white, female, with at least two ‘co-morbidities’, such as diabetes, lung or heart disease
  • Cognitive impairment, also referred to as ‘brain fog’, occurs as a predominant symptom in a sub-set of patients who tend to be older and male
  • A biological marker associated with inflammation, C-Reactive Protein (CRP), is elevated in all but the most mild of post-hospital cases

The majority of survivors who left hospital following COVID-19 did not fully recover five months after discharge and continued to experience negative impacts on their physical and mental health, as well as ability to work, according to results released by the PHOSP-COVID study today. Furthermore, one in five of the participant population reached the threshold for a new disability.

The UK-wide study, which is led by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre – a partnership between Leicester’s Hospitals, the University of Leicester and Loughborough University - and jointly funded by the NIHR and UK Research and Innovation, analysed 1077 patients who were discharged from hospital between March and November 2020 following an episode of COVID-19.

Researchers found that each participant had an average of nine persistent symptoms. The ten most common symptoms reported were: muscle pain, fatigue, physical slowing down, impaired sleep quality, joint pain or swelling, limb weakness, breathlessness, pain, short-term memory loss, and slowed thinking.

Patients were also assessed for mental health. The study reports that over 25 per cent of participants had clinically significant symptoms of anxiety and depression and 12 per cent had symptoms of post-traumatic stress disorder (PTSD) at their 5-month follow-up.

Of the 67.5 per cent of participants who were working before COVID, 17.8 per cent were no longer working, and nearly 20 per cent experienced a health-related change in their occupational status.

Professor Chris Brightling, a professor of respiratory medicine at the University of Leicester and the chief investigator for the PHOSP-COVID study, said:

While the profile of patients being admitted to hospital with COVID-19 is disproportionately male and from an ethnic minority background, our study finds that those who have the most severe prolonged symptoms tend to be white women aged approximately 40 to 60 who have at least two long term health conditions, such as asthma or diabetes.

The researchers were able to the classify types of recovery into four different groups or ‘clusters’ based on the participants’ mental and physical health impairments.

One cluster group in particular showed impaired cognitive function, or what has colloquially been called ‘brain fog’. Patients in this group tended to be older and male. Cognitive impairment was striking even when taking education levels into account, suggesting a different underlying mechanism compared to other symptoms.

Dr Rachael Evans, an associate professor at the University of Leicester and respiratory consultant at Leicester’s Hospitals, said:

Our results show a large burden of symptoms, mental and physical health problems and evidence of organ damage five months after discharge with COVID-19. It is also clear that those who required mechanical ventilation and were admitted to intensive care take longer to recover. However, much of the wide variety of persistent problems was not explained by the severity of the acute illness - the latter largely driven by acute lung injury - indicating other, possibly more systemic, underlying mechanisms.

The research has also uncovered a potential biological factor behind some post-COVID symptoms.

Professor Louise Wain, GSK/British Lung Foundation Chair in Respiratory Research at the University of Leicester and co-investigator for the PHOSP-COVID study, said:

When we looked at the symptom severity of patients five months after they were discharged from hospital, we found that in all but the mildest cases of persistent post-COVID symptoms, levels of a chemical called C-reactive protein [CRP], which is associated with inflammation, were elevated.

From previous studies, it is known that systemic inflammation is associated with poor recovery from illnesses across the disease spectrum. We also know that autoimmunity, where the body has an immune response to its own healthy cells and organs, is more common in middle-aged women. This may explain why post-COVID syndrome seems to be more prevalent in this group, but further investigation is needed to fully understand the processes. The evidence for different recovery ‘clusters’, and ongoing inflammation, really is important in guiding how we conduct further research into the underlying biological mechanisms that drive ‘Long-COVID’.

One of the purposes of the PHOSP-COVID study is to measure the impact of medicines given during hospitalisation to see if they affect patients’ recovery. Early indicators from the study show that while giving corticosteroids is a factor in reducing mortality in hospital, it does not appear to have an impact on longer term recovery.

There are more than 300,000 post-hospitalisation survivors in the UK that have been discharged from hospital following COVID-19. While the study only represents a small sample of these patients, and participants are younger than the whole population in the UK that survived hospitalisation for COVID-19 infection, this is the largest study to report in detail on prospectively assessed outcomes across multiple UK centres to describe the impact of COVID-19 on medium term health of survivors.

Professor Brightling added:

Our findings support the need for a proactive approach to clinical follow-up with a holistic assessment to include symptoms, mental and physical health, but also an objective assessment for cognition. The four severity clusters highlight potential to stratify care, but also the need for wide-access to post-COVID19 holistic clinical services to include mental health, memory and cognition, and rehabilitation services.

Continued study of the trajectory of recovery over a longer timeframe, coupled with greater understanding of the biology underpinning post-COVID symptoms, will further inform approaches to the clinical management post-COVID19 infection. As such, patients in the study will be assessed again at 12 months to help gather more data to support this learning.

Professor Chris Whitty, Chief Medical Officer and co-lead for the National Institute for Health Research, said:

We are in the foothills of our understanding of long term effects of COVID. This research provides useful information on the debilitating effects of COVID some people are living with months after being hospitalised.

It is important that we work out what exactly the various elements of what is currently termed ‘Long Covid’ are so we can target actions to prevent and treat people suffering with long term effects.

Health and Social Care Secretary, Matt Hancock, said:

I know Long COVID can have a lasting and debilitating impact on the lives of those affected and I'm determined to improve the care we can provide.

Studies like this help us to rapidly build our understanding of the impact of the condition and we are working to develop new research so we can support and treat people.

We are learning more about Long-COVID all the time and have given £20 million research funding to support innovative projects, with clinics established across the country to help improve the treatment available.

Professor Fiona Watt, Executive Chair of the Medical Research Council, part of UKRI, said:

The initial findings from this study are that most patients hospitalised with Covid-19 are still suffering from effects of the disease five months on. Whilst this is clearly a concern, the new findings will help pave the way to improving patient recovery. The more we understand about what risk factors make someone less likely to recover fully, the better care and treatment we can offer to those patients who need it most.

NHS medical director Stephen Powis said:

Long covid can have a significant impact on someone’s quality of life, which is exactly why in addition to funding and driving world-leading research into the condition, the NHS has invested millions in opening dozens of long covid clinics to help people get back to good health. As we have throughout the pandemic, as new evidence and treatments emerge, the NHS will respond quickly and get the latest treatments to patients quickly, as we did with dexamethasone, which was used on the front line of patient care on the day it was approved and which has since saved one million lives around the world.

Rebecca Brown, Acting Chief Executive at Leicester’s Hospitals, said:

I am extremely proud of everyone on the PHOSP-COVID team who has been working hard on this important research. With this new data, they are shining a light on the longer term impacts of COVID-19. From the evidence presented today we can start to see which patients are most likely to be affected, and how, so we can tailor treatments to help them make the best recovery possible.


Notes for editors

Trial registration: ISRCTN10980107; Funding: UKRI/NIHR

PHOSP-COVID is a multi-centre, UK-wide, observational study of patients discharged from hospital following a clinical diagnosis of COVID-19. It has been awarded £8.4million jointly by UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR). This study is one of a number of COVID-19 studies that have been given urgent public health research status by the Department of Health and Social Care.

Led by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre - a partnership between the University Hospitals of Leicester NHS Trust, the University of Leicester and Loughborough University - the PHOSP-COVID study draws on expertise from a consortium of leading researchers and clinicians from across the UK to assess the impact of COVID-19 on patient health and their recovery. In total, 10,000 participants are expected to take part in the study.

The first three clusters included 17-21 per cent of the participants each, whereas cluster 4 represented 46 per cent of the participants.

  • Cluster 1
    Patients had very severe physical and mental health impairment with poor cognition; less than 3% felt recovered. They were more obese and had multiple long term health conditions.
  • Cluster 2
    Patients had severe physical and mental health impairment with minimal effect on cognition; 7% felt recovered. They tended to be more obese and had multiple long term health conditions.
  • Cluster 3
    Patients had moderate physical and mental health impairment but with more pronounced cognitive impairment. In this cluster, 36% felt recovered. They were older, more male, less obese, and less likely to have multiple long term health conditions. Cognitive impairment remained very striking in this cluster even after accounting for education level.
  • Cluster 4
    43% felt recovered and physical and mental health impairment was mild.

*Based on the Science Media Centre press release labelling system

For more information:

Rachael Dowling, head of research communications, Leicester’s Hospitals/NIHR Leicester Biomedical Research Centre – rachael.dowling@uhl-tr.nhs.uk; 07950 891193

Mina Sharma, media relations manager, University of Leicester – press@leicester.ac.uk; 07919 933824

Photographs of Professor Chris Brightling, Dr Rachael Evans and Professor Louise Wain can be accessed here: https://drive.google.com/drive/folders/17IOn8kdB41lmrE2BN6YaebPCbaPJnhlK?usp=sharing

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