People who were hospitalised with COVID-19 and continued to experience symptoms at five months show limited further recovery one year after hospital discharge, according to the latest results of the PHOSP-COVID study, released as a pre-print on medRxiv today.
Pre-print Observational People*
The study, 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 MRC-UK Research and Innovation(UKRI), also confirmed earlier research that people who were less likely to make a full recovery from COVID-19 were female, obese, and required invasive mechanical ventilation (IMV) to support their breathing during their hospital stay.1
Researchers from 53 institutions and 83 hospitals across the UK assessed 2,230 adults who had been hospitalised with COVID-19. All participants completed a five-month assessment; so far, 807 people have completed both the five-month and 12-month assessments. Recovery was measured using patient-reported data, physical performance and organ function tests. Participant blood samples at the five-month visit were analysed for around 300 substances linked to inflammation and immunity.
They found that one year after hospital discharge, less than 3 in 10 patients on the study reported they felt fully recovered, largely unchanged from 2.5 in 10 at five months. The most common ongoing symptoms were fatigue, muscle pain, physically slowing down, poor sleep and breathlessness. Participants felt their health-related quality of life remained substantially worse one year after hospital discharge, compared to pre-COVID. This suggests the physical and mental health impairments reported in the study are unlikely to be pre-existing conditions.
A cluster analysis, which is a mathematical method to group participants according to similar traits and characteristics, identified four distinct groups based on the severity of physical, mental and cognitive impairments experienced at five months. The number of persistent symptoms was much higher in the ‘very severe’ group compared to the ‘mild’ group. In all of these clusters, there was little improvement in physical and mental health from the five-month to one-year assessments.
The researchers compared the blood profiles across the four clusters. They identified higher levels of substances associated with whole-body inflammation and molecules associated with tissue damage and repair, in participants with very severe-Long COVID compared to mild. They also found a pattern of substances linked to poor cognition (‘Brain fog’) in the cluster of patients reporting symptoms such as ‘brain fog’ or slowed thinking, suggesting possible neuro-inflammation.
Professor Chris Brightling, NIHR Senior Investigator and Professor of Respiratory Medicine at the University of Leicester, and Chief Investigator for the PHOSP-COVID study, said: “The PHOSP-COVID study is further evidence of the UK’s ability to combine expertise across both disease area and geography to rapidly gather data to help us understand the longer term implications of Long-COVID in hospitalised patients with persistent symptoms. Our findings show that people who were hospitalised and went on to develop Long-COVID are not getting substantially better a year after they were discharged from hospital. Many patients in our study had not fully recovered at five months and most of these reported little positive change in their health condition at one year.
“When you consider that over half a million people in the UK have been admitted to hospital as a result of COVID-19, we are talking about a sizeable population at risk of persistent ill-health and reduced quality of life.”
Dr Rachael Evans, an Associate Professor at the University of Leicester, Respiratory Consultant at Leicester’s Hospitals, and a lead author of the paper, said: “The findings that many patients had not fully recovered one year after leaving hospital indicate that healthcare professionals will need to proactively continue assessing their patients for some time to come in order to identify their ongoing healthcare needs and provide support.
“However, we urgently need healthcare packages and medicines that target the potentially treatable traits of Long-COVID to help people feel better and get back to their normal lives. Without these, Long-COVID has the potential to become highly prevalent as a new long-term condition.”
Professor Louise Wain, GSK-BLF Chair in Respiratory Research at the University of Leicester and a lead author of the paper, said: “The good news is that we have identified some differences in the blood samples of those who are still experiencing the long-term physical and cognitive effects of their COVID-19 hospital admission. These differences give us clues about the potential underlying mechanisms and suggest that we may be able to use existing medicines that target these mechanisms to help these subgroups of patients.”
Professor Nick Lemoine, Chair of NIHR’s Long-COVID funding committee and Medical Director of the NIHR Clinical Research Network (CRN), said: “These results bring into sharp focus the extent to which Long-COVID affects people’s long term health and quality of life. Only by funding and delivering this research, can we seek to improve health outcomes and configure healthcare services to provide the absolute best care.
“NIHR has awarded more than £50 million into research covering the full spectrum of causes, mechanisms, diagnosis, treatment and rehabilitation of Long-COVID; a demonstration of our commitment to tackle this long term condition.”
Professor Fiona Watt, Executive Chair of the Medical Research Council, which co-funded the study, said: “This new evidence from the PHOSP-COVID study provides us with vital information about the long term effects associated with COVID-19 in patients who were treated in hospital. The information will inform the development of effective ways to help Long-COVID patients.”
Professor Melanie Davies, Director of the NIHR Leicester BRC, said: “This is one of two Urgent Public Health studies into COVID-19 led by the NIHR Leicester Biomedical Research Centre, demonstrating our combined academic and clinical expertise and capabilities in co-ordinating important national research programmes.
“The results from the PHOSP-COVID study not only provide further evidence of the impact and scale of long Covid in patients who were treated in hospital, but gives insights into where potential treatment options may lie.”
Richard Mitchell, Chief Executive at Leicester’s Hospitals, said: “Leicester’s Hospitals working together with academic partners have an excellent track record of leading and delivering COVID-19 research. The latest findings of the PHOSP-COVID study are incredibly important because we know there is a growing patient population with long COVID. These patients will continue to require support to manage persistent symptoms after they have been discharged from hospital.
“I am grateful that so many patients have joined the study and I am hopeful that targeted treatments can be tested and later made available to support patients achieve better health outcomes.”
Professor Nishan Canagarajah, President and Vice-Chancellor at the University of Leicester said: “This is extremely significant research, which will help to improve our understanding of and shape the treatment provided to those suffering from the long term impact of COVID.
“I am proud of the pioneering work taking place here in Leicester – in our Centenary year our academics continue to produce world-changing research in partnership with our collaborators.”
The consortium acknowledges that there may be self-selection bias in the patients returning for one-year visits, although from the data it appears that there are no clear differences between the patients attending the one-year follow-up and the larger participant population in the wider study including their recovery at five months. Assuming all the participants who had missing data at one year had either not recovered or were fully recovered, the adjusted figures are 2 in 10 or 6 in 10 people recovering from COVID-19 at one year, respectively.
The PHOSP-COVID study is available as a pre-print, which means it is yet to be checked by other scientists.
 Evans RA, McAuley H, Harrison EM et al. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study. Lancet Respir Med 2021 Nov 9(11):1275-1287