PHOSP-COVID Post-hospitalisation COVID-19 study: a national consortium to understand and improve long-term health outcomes
Lead Research Organisation:
University of Leicester
Department Name: Infection Immunity and Inflammation
Abstract
The COVID-19 pandemic has tragically led to severe acute illness, hospitalisation and death. Beyond the health of those affected, it has had widespread economic, psychological and societal effects. The clinical spectrum is broad, ranging from those with no or minimal symptoms to severe pneumonia in 15-20% with evidence of widespread disease beyond the lung. As we emerge from the first wave of the pandemic we have new insights into the acute phase of this disease but very little information concerning longterm effects of COVID-19 and the ongoing medical, psychological and rehabilitation needs of these patients. We shall establish a national consortium and a research platform embedded within clinical care to understand and improve long-term outcomes for survivors following hospitalisation with COVID-19. We have built the consortium from existing expert groups across the UK and shall use standardised assessments of patients, including advanced imaging, recording of information and collection of samples. This study will provide us with a comprehensive understanding of the impact on the health of those that have been hospitalised with COVID-19. This will enable trials of new strategies of clinical care including personalised treatments to improve the long-term outcome of current and future COVID-19 survivors.
Technical Summary
The SARS-CoV-2 (COVID-19) pandemic, has caused significant mortality and morbidity, alongside economic, psychological and societal effects. Over 100,000 people have been hospitalised in the UK with an in-hospital mortality of 26%. In addition to severe pneumonia, there is evidence of widespread pathology beyond the lung. To understand and improve long-term outcomes for survivors following hospitalisation with COVID-19, we shall establish a national platform embedding research into a standardised clinical pathway and biosampling integrated with ISARIC-4C and utilising the NIHR Bioresource. This will enable detailed clinical phenotyping of individuals. We propose to analyse routine
clinical data with linkage to retrospective and prospective health and social care records (Tier 1), enhanced clinical data and research-specific biosampling (Tier 2) and re-call of participants by genotype and phenotype for more detailed studies (Tier 3). We shall recruit 10000 individuals with a minimum of 5000 in Tier 2. We aim to i) determine the short to long-term chronic health (and health economic) sequelae of COVID-19 infection in post-hospitalisation survivors; to define demographic, clinical and molecular biomarkers of the susceptibility, development, progression and resolution of these health sequelae, ii) to understand the impact of interventions during the acute illness on these long-term sequelae and iii) to build the foundation for multiple indepth studies e.g. lung fibrosis, pulmonary and systemic vasculature, cardiometabolic, renal, sarcopaenia, rehabilitation, mental health and neurological disease. Our findings will
inform precision medicine in at risk groups by directing new clinical trials and care for current and future post-COVID-19 patients.
clinical data with linkage to retrospective and prospective health and social care records (Tier 1), enhanced clinical data and research-specific biosampling (Tier 2) and re-call of participants by genotype and phenotype for more detailed studies (Tier 3). We shall recruit 10000 individuals with a minimum of 5000 in Tier 2. We aim to i) determine the short to long-term chronic health (and health economic) sequelae of COVID-19 infection in post-hospitalisation survivors; to define demographic, clinical and molecular biomarkers of the susceptibility, development, progression and resolution of these health sequelae, ii) to understand the impact of interventions during the acute illness on these long-term sequelae and iii) to build the foundation for multiple indepth studies e.g. lung fibrosis, pulmonary and systemic vasculature, cardiometabolic, renal, sarcopaenia, rehabilitation, mental health and neurological disease. Our findings will
inform precision medicine in at risk groups by directing new clinical trials and care for current and future post-COVID-19 patients.
Publications
Adeloye D
(2021)
The long-term sequelae of COVID-19: an international consensus on research priorities for patients with pre-existing and new-onset airways disease.
in The Lancet. Respiratory medicine
Astley J
(2023)
Implementable Deep Learning for Multi-sequence Proton MRI Lung Segmentation: A Multi-center, Multi-vendor, and Multi-disease Study
in Journal of Magnetic Resonance Imaging
Bangash MN
(2022)
Impact of ethnicity on the accuracy of measurements of oxygen saturations: A retrospective observational cohort study.
in EClinicalMedicine
Cassar M. P.
(2021)
Longitudinal trajectory of cardiac magnetic resonance and cardiopulmonary exercise testing findings in moderate to severe COVID-19 and association with symptoms
in EUROPEAN HEART JOURNAL
Cassar MP
(2021)
Symptom Persistence Despite Improvement in Cardiopulmonary Health - Insights from longitudinal CMR, CPET and lung function testing post-COVID-19.
in EClinicalMedicine
Daines L
(2023)
Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.
in ERJ open research
Elneima O
(2023)
Cohort Profile: Post-hospitalisation COVID-19 study (PHOSP-COVID)
Evans RA
(2021)
Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.
in The Lancet. Respiratory medicine
| Description | The severity of illness following infection with COVID-19 has decreased because of public health policies, vaccination and acute anti-viral and anti-inflammatory therapies. However, in the wake of the pandemic post-acute sequelae of COVID-19 known as 'Long-COVID' has emerged. Long-COVID is a chronic illness in people that continue to experience ongoing symptoms and disability. The PHOSP-COVID consortium was established in August 2020 and its aims are: i) to describe the impact of long-COVID on people that were hospitalised with COVID-19 infection, ii) what features are associated either with good or poor recovery, iii) what is the underlying cause of long-COVID, iv) is long-COVID altered by treatments given for the acute infection and v) can we develop treatments for people with long-COVID to improve recovery. The PHOSP-COVID consortium includes 83 hospital, over 25 universities, 10+ patient groups and charities and 500+ researchers. We recruited people to three tiers of research tier 1 questionnaires, use of routine data and a saliva sample for genetic testing, tier 2 an early (5 month) and later 12 month visit that included detailed questionnaires, exercise tests, sampling such as blood tests and tier 3 whereby people had additional visits for more detailed immune tests and magnetic resonance imaging. Recruitment has been completed across the 4 nations. 7935 participants recruited to the study (Tier 1: 5231, Tier 2: 2704 with Tier 3 participants included in Tier 2). Patients, clinicians and scientists worked together on developing priority research questions and throughout the study, there has been close engagement between the consortium, patients involved in the study and the wider public. We found that at 5 months only about 30% of people that were hospitalised due to COVID-19 infection had fully recovered. This proportion was similar after 1 year with only marginal improvement from 5 months to 1 year. You were more likely not to have recovered if you were a woman, were between the ages of 35-65 years old, were obese, had multiple long-term conditions prior to COVID-19 infection or required mechanical ventilation whilst hospitalised. We found that the treatments given for the acute infection such as corticosteroids did not affect the likelihood of recovery. We found that the severity of symptoms largely grouped together except for 'brain-fog', which could occur on its own. Those with the most severe symptoms had evidence of persistent inflammation measured with a simple blood test called CRP. This measure is associated with a specific inflammatory pathway and with industry colleagues; we will be testing whether treatments targeting this pathway improve recovery. We have studied the impact on all the body's systems with magnetic resonance imaging and found changes in the brain, heart, lungs and liver. In the lungs, about 5% have evidence of early lung scarring on CT scans. We are looking at how these changes link to severity of disease and impairments in the immune response. We have found several important features in the immune response. In older people with long-COVID the immune response is decreased, there is increased auto-immunity with activation of specific types of immune cells. we have found increased complement activation. We have found that exercise capacity is reduced and are testing whether in some people tailored exercise programmes might be helpful and can impact on cell mediated immunity. We have identified key changes in prothrombotic substances that relate to different patterns of poor cognition. We have described changes in sleep patterns and quality related to chronic ongoing symptoms. We have contributed to the world's largest genetics study of long-covid. More detailed work is ongoing looking into effects on all the organs of the body and we anticipate this will help to develop new tests, new treatments and impact on healthcare. |
| Exploitation Route | in discussion with international health organisations e.g. WHO, NIH, ERS on policy, future collaborations and policy. In discussion with major pharma on partnerships and intervention studies including possible major EU bids. |
| Sectors | Healthcare |
| URL | https://www.phosp.org/ |
| Description | Description of: New disease entity - Long-COVID. New health care systems and clinics understanding of risk factors understanding of underlying mechanisms Development of biomarkers and new interventions. influence on national and international healthcare policy e.g. guidelines, government advisory panels. |
| First Year Of Impact | 2000 |
| Sector | Healthcare |
| Guideline Title | NICE guideline for Long-COVID |
| Description | National COVID policy |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical guidelines |
| Impact | PHOSP-COVID has greatly influenced the set-up on the national network of long-COVID clinics. |
| Description | National COVID policy |
| Geographic Reach | National |
| Policy Influence Type | Citation in other policy documents |
| Impact | Underpinned the research strategy for long-COVID nationally and influenced discussions at SAGE and DHSC long-COVID task force. |
| Title | Supplementary information files for The effect of COVID rehabilitation for ongoing symptoms post hospitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium |
| Description | Supplementary files for article The effect of COVID rehabilitation for ongoing symptoms post hospitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium Introduction: Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. Methods and analysis: This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform (www.yourcovidrecovery.nhs.uk). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. Ethics and dissemination: Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Article summary Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| URL | https://repository.lboro.ac.uk/articles/dataset/Supplementary_information_files_for_The_effect_of_CO... |