70% 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. Furthermore, one in five of the participant population reached the threshold for a new disability.

The UK-wide study, led by a research consortium including Guy’s and St Thomas’ NHS Foundation Trust, King’s College Hospital NHS Foundation Trust and King’s College London, 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 five-month follow-up.

Of the 68% of participants who were working before COVID, 20% were no longer working, and nearly 20 per cent experienced a health-related change in their occupational status.

Professor Chris Brightling, 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. 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.

Professor Nick Hart, professor of respiratory and critical care medicine at Guy’s and St Thomas’, said: “Our results show the ongoing physical and mental health burden on many of those hospitalised by COVID-19 in the first wave. These new findings must be investigated further and compared with those patients admitted to hospital in the second wave. Importantly, these data provide the support for the development of interventions to treat patients following hospital discharge. In addition, we need much needed research that describes in detail the difference between the long-term effects of severe COVID-19 and the long COVID condition that follows less severe COVID-19 infection.”

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 COVID-19 post-hospitalisation survivors in the UK. 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.

Health and Social Care Secretary, Matt Hancock, said: “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.”

The study was jointly funded by the National Institute for Health Research and UK Research and Innovation.

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

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