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.
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, including Manchester University NHS Foundation Trust (MFT), Salford Royal NHS Foundation Trust (now the Northern Care Alliance NHS Foundation Trust), and The University of Manchester (UoM), 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.”
Clinicians, researchers, and patients from across Greater Manchester have played a critical role in the PHOSP-COVID study. MFT was the second highest recruiter in the country, running the study across several sites in the city region.
Nationally, Professor Neil Hanley, Vice-Dean for Research and Innovation at UoM and a Professor of Medicine in Endocrine Science, and Professor Alex Horsley, Respiratory Consultant and Medical Director at NIHR Manchester Clinical Research Facility at Wythenshawe Hospital (part of MFT), both sit on the PHOSP-COVID Executive Committee.
Professor Horsley, who led the study at MFT, is also a researcher within the NIHR Manchester Biomedical Research Centre’s Respiratory Medicine Theme, sits on the study Core Management Group and was part of team behind the paper. He said: “The multidisciplinary team at MFT have done a fantastic job in recruiting more than 300 patients to the PHOSP-COVID study, and we are really pleased to have contributed significantly to this national vital study.
“That is now more than 300 people across Greater Manchester we have been monitoring to see the impact of Long -COVID on their day-to-day health and general wellbeing. As the results have shown, there has been a huge impact on full recovery from COVID-19 for many patients. This study is still ongoing, and we will continue to follow-up with our research participants to assess their continuing health and feed the results back into the study to enhance our understanding of Long-COVID.”
Greater Manchester will continue to contribute to the findings for Long-COVID through further studies and grants.
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.”
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.