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.

People

ORCID iD

Christopher Brightling (Principal Investigator)
Nicholas Hart (Co-Investigator)
James Wild (Co-Investigator)
Nick Maskell (Co-Investigator)
Dhruv Parekh (Co-Investigator)
Gisli Jenkins (Co-Investigator)
Raminder Aul (Co-Investigator)
Iain McInnes (Co-Investigator)
Mark Toshner (Co-Investigator) orcid http://orcid.org/0000-0002-3969-6143
Mark Jones (Co-Investigator) orcid http://orcid.org/0000-0001-6308-6014
Ling-Pei Ho (Co-Investigator)
Louise Wain Taylor (Co-Investigator) orcid http://orcid.org/0000-0003-4951-1867
Alfred Thompson (Co-Investigator)
Sarah Rowland-Jones (Co-Investigator)
Malcolm Semple (Co-Investigator)
John Geddes (Co-Investigator)
David Lomas (Co-Investigator)
Aziz Sheikh (Co-Investigator)
Michael Marks (Co-Investigator)
Dana Dawson (Co-Investigator)
Neil Hanley (Co-Investigator)
Paul Pfeffer (Co-Investigator)
John Kenneth Baillie (Co-Investigator) orcid http://orcid.org/0000-0001-5258-793X
Adrian Martineau (Co-Investigator) orcid http://orcid.org/0000-0001-5387-1721
Dan Wootton (Co-Investigator)
Keir Lewis (Co-Investigator)
Matt Brown (Co-Investigator) orcid http://orcid.org/0000-0003-0538-8211
Liam Heaney (Co-Investigator)
Alexander Robert Horsley (Co-Investigator) orcid http://orcid.org/0000-0003-1828-0058
Elizabeth Sapey (Co-Investigator) orcid http://orcid.org/0000-0003-3454-5482
Stefan Neubauer (Co-Investigator)
Rachael Evans (Co-Investigator) orcid http://orcid.org/0000-0002-1667-868X
James Chalmers (Co-Investigator)
PAUL BEIRNE (Co-Investigator)
Colin Berry (Co-Investigator) orcid http://orcid.org/0000-0002-4547-8636
Anthony De Soyza (Co-Investigator)
Edwin Chilvers (Co-Investigator)

Publications

10 25 50

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Stewart I (2023) Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study in American Journal of Respiratory and Critical Care 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 that exercise capacity is reduced and are testing whether in some people tailored exercise programmes might be helpful.
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.
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.