The UK Interstitial Lung Disease Long-COVID19 study (UKILD-Long COVID): understanding the burden of Interstitial Lung Disease in Long COVID.

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

Many recovering COVID-19 patients suffer from long term symptoms, including breathlessness and fatigue, so-called "Long COVID". Recent data suggest that between 10-20% of patients who do not go into hospital and 40-60% of people discharged from hospital suffer from symptoms of Long COVID.

The COVID-19 pandemic has led to a huge number of infected people throughout the world with a substantial number requiring hospital-based care. In the UK alone, there have been over 3.5 million people known to be infected of whom more than 350,000 people were hospitalised, with over 25,000 admitted to intensive care units.

The commonest reason for hospital admission is COVID pneumonitis. If this progresses to Adult Respiratory Distress Syndrome, patients may be admitted to Intensive Care Wards , where they could be placed on a ventilator to support them through their illness.

Recent analysis indicates that inflammatory and scarring lung diseases (known as Interstitial Lung diseases - ILD) are a major complication of COVID pneumonitis and occur in approximately 20% of patients discharged from hospital. The figure is thought to be even higher in patients discharged from Intensive Care Units. Although the exact number of people affected is not yet known, there is an urgent need to identify and prevent the development of this potential severe complication, which can lead to irreversible scarring.

Therefore, to improve outcomes for survivors of COVID pneumonitis we will undertake a clinical study to identify how many people develop ILD following COVID-19, what types of ILD they develop (is it predominantly inflammation or scarring) and why they do so. We will ask patients with possible ILD if they would be willing to have a CT scan to confirm whether they have this disease. If they do, we will invite these patients to undergo investigations using a range of new technologies. These will include Xenon Magnetic Resonance Imaging to get more detailed analysis of the changes in the function of different parts of the lung and Bronchoalveolar Lavage to analyse cells from the lung to understand whether the severity of COVID-19 or its treatments make a difference to the development of ILDs. We will identify whether COVID-19 leads primarily to either inflammatory or scarring disease and whether this disease gets better or worse in the year after they are discharged from hospital. Finally, we will try to understand why some patients get severe lung disease following COVID-19, and others don't, and identify blood markers and genes that increase the risk of developing long-term scarring, so that we can determine how to treat patients and prevent the development of substantial scarring.

Understanding these questions will help us to develop treatment strategies to prevent the development of severe scarring and disability following COVID-19 infection.

Technical Summary

The COVID-19 pandemic has caused significant worldwide mortality and morbidity with over 3.5 million people infected and more than 350,000 people hospitalised in the UK. Current estimates suggest 10-20% of non-hospitalised patients and 40-60% of hospitalised patients have long term symptoms, including breathlessness and fatigue, so-called "Long COVID". Emerging radiological and physiological features suggest Interstitial Lung diseases (ILD) including organising pneumonia and pulmonary fibrosis occur in up to 20% of hospitalised patients, although the precise burden and natural history of Long COVID related ILD (LCILD) is not clear. Given the large number of patients with persisting breathlessness there is an urgent need to identify and prevent the development LCILD.
To improve outcomes for survivors of COVID-19 we will a) determine the prevalence of ILD
following COVID-19, stratified by severity of infection and treatment, b) describe the phenotypes, c) determine the natural history and d) identify pathogenic mechanisms and biomarkers of LCILD.
Patients with proven COVID-19 will be recruited and the proportion of patients with symptoms, signs and investigations consistent with ILD between 3 and 6 months will be documented. In patients where ILD is suspected clinically this will be confirmed by Computerised Tomography (CT) scanning and patients will be stratified by pre-existing ILD, hospitalisation status, and therapy received. A subgroup of patients with proven LCILD will be re-consented for 12-month follow-up and deep phenotyping including 129Xenon-MRI and bronchoalveolar lavage.
These data will define the burden of LCILD and inform the design of clinical trials to assess
potential therapies to modulate progression of LCILD.

People

ORCID iD

Gisli Jenkins (Principal Investigator)
Ian Hall (Co-Investigator)
Simon Leonard Francis Walsh (Co-Investigator) orcid http://orcid.org/0000-0003-0497-5297
Lisa Spencer (Co-Investigator)
Louise Wain Taylor (Co-Investigator) orcid http://orcid.org/0000-0003-4951-1867
Ling-Pei Ho (Co-Investigator)
Rachel Clare Chambers (Co-Investigator) orcid http://orcid.org/0000-0003-1370-9417
Karen Piper Hanley (Co-Investigator)
Pilar Rivera-Ortega (Co-Investigator) orcid http://orcid.org/0000-0002-7960-8822
Malcolm Gracie Semple (Co-Investigator) orcid http://orcid.org/0000-0001-9700-0418
Joseph Jacob (Co-Investigator) orcid http://orcid.org/0000-0002-8054-2293
Bibek Gooptu (Co-Investigator)
Iain Stewart (Co-Investigator) orcid http://orcid.org/0000-0002-1340-2688
Jane A Mitchell (Co-Investigator)
Nazia Chaudhuri (Co-Investigator)
Philip Molyneaux (Co-Investigator) orcid http://orcid.org/0000-0003-1301-8800
James Wild (Co-Investigator) orcid http://orcid.org/0000-0002-7246-8660
John Blaikley (Co-Investigator)
Mark Glynne Jones (Co-Investigator) orcid http://orcid.org/0000-0001-6308-6014
Peter Michael George (Co-Investigator) orcid http://orcid.org/0000-0003-1316-4891
John Simpson (Co-Investigator) orcid http://orcid.org/0000-0003-4731-7294
Jennifer Quint (Co-Investigator) orcid http://orcid.org/0000-0003-0149-4869
John Kenneth Baillie (Co-Investigator) orcid http://orcid.org/0000-0001-5258-793X
Neil Hanley (Co-Investigator)
Joanna Catherine Porter (Co-Investigator) orcid http://orcid.org/0000-0002-7307-169X
Fergus Gleeson (Co-Investigator)
Richard Allen (Researcher) orcid http://orcid.org/0000-0002-8450-3056
Emma Kate Denneny (Researcher)

Publications

10 25 50
 
Description We have discovered that between 5-10% of patients hospitalised with COVID-19 are at risk of Interstitial Lung Damage. Interstitial Lung Damage is more likely in patients with severe COVID pneumonitis and evidence of abnormalities on chest X-ray and reduced gas transfer on lung function assessment. However, we have also found that patients with risk factors for ILD Damage are not getting investigated thoroughly enough for a variety of reasons including backlogs in service requirements following COVID and restructuring of services due to infection control policy changes.
Exploitation Route This will hopefully prompt more thorough investigation of patients with persistent breathlessness following Post COVID Pneumonitis.
Sectors Healthcare,Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology

URL https://doi.org/10.1101/2022.03.10.22272081
 
Description Argentinian Respiratory Society, Buenos Aires, Argentina 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk entitled: "Dangerous relationships: COVID-19 and pulmonary fibrosis" to clinicians in Argentina via zoom.
Year(s) Of Engagement Activity 2021
 
Description British Society of Thoracic Imaging, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Gave lecture to the national pulmonary radiologist meeting entitled "Post COVID - is there calm after the storm? A clinical viewpoint!" which lead to a lot of lively discussion.
Year(s) Of Engagement Activity 2021
 
Description British Thoracic Society meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Talk at the online British Thoracic Society summer meeting which is the premier educational conference for respiratory practitioners in UK. Lots of questions and requests for further engagement activities.
Year(s) Of Engagement Activity 2021
 
Description Cambridge Respiratory Research Seminars, University of Cambridge, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Talk entitled Understanding Pulmonary Fibrosis in the Post COVID World
Year(s) Of Engagement Activity 2021
 
Description Cardiorespiratory Interface Section Seminar, Imperial College London,UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Online seminar entitled: Priming the alveolus: do your genes and the environment matter in Acute Lung Injury? Lots of questions asked.
Year(s) Of Engagement Activity 2021
 
Description Discovery Medicine Clinical Insight Session, GlaxoSmithKline 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Provided a zoom lecture to GSK about how the learnings from COVID19 may inform future studies in IPF entitled "What can the COVID-19 pandemic teach us about Idiopathic Pulmonary Fibrosis?" Lots of positive feedback and questions asked.
Year(s) Of Engagement Activity 2022
 
Description Elle Magazine Interview 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Gave an interview about Long COVID which was featured in a magazine article about Long COVID
Year(s) Of Engagement Activity 2021
URL https://www.elle.com/uk/life-and-culture/elle-voices/a37325979/breathing-long-covid/
 
Description European Pulmonary Fibrosis Summit, Europe 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Plenary Lecture "The joint challenges of Covid 19 & Curing the Incurable" at the major patients engagement conference in Europe
Year(s) Of Engagement Activity 2021
URL https://www.eu-ipff.org/european-pf-patient-summit-2021
 
Description Global Health Asia Pacific Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interviewed for Global Health Asia-Pacific magazine about Long COVID related breathlessness. Published June 2021
Year(s) Of Engagement Activity 2021
 
Description Gordon Research Conference one Alveolar Repair and Regeneration 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk entitled "Alveolar Injury and the Development of Post COVID Fibrosis." which lead to considerable engagement and a new collaboration.
Year(s) Of Engagement Activity 2021
 
Description Interview with Dail Mail 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed by Daily Mail about the NICE decision to offer nintedanib to patients with progressive pulmonary fibrosis.
Year(s) Of Engagement Activity 2021
URL https://www.dailymail.co.uk/health/article-10147525/Life-extending-drug-sufferers-asbestos-lung-dise...
 
Description KUCI meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Annual Kings College London, University College London and Imperial College London (KUCI) Respiratory Society meeting Brockenhurst, UK.
Year(s) Of Engagement Activity 2021
 
Description Nursing Australia Podcast 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Interviewed about long COVID by the Nursing Australia podcast organisation which generated a lot of interest.
Year(s) Of Engagement Activity 2021
URL https://www.apna.asn.au/education/nursing-australia-podcast/ep18#s1
 
Description Primary Care Issues and Answers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Gave a lecture to a primary care conference entitled Long Covid and respiratory disease: Red flags and top tips.
Year(s) Of Engagement Activity 2021
 
Description Pulmonary and Critical Care Grand Rounds, University of Birmingham Alabama. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Visiting Professor (via Zoom) at the University of Birmingham, Alabama, USA and had a series of one to one meetings with potential collaborators and gave lecture at the the Univesirty of Alabama Ground Rounds.
Year(s) Of Engagement Activity 2021
 
Description The Annual Margaret Turner Warwick Lecture and Inaugural Lecture for the MTW Centre for Fibrosing Lung Diseases, Imperial College, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Annual lecture entitled: curing the incurable.
Year(s) Of Engagement Activity 2021
URL https://www.youtube.com/watch?v=K6rgn8P_1fI
 
Description The Times Interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed by the Times about the possible effect of COVID-19 and Influenza on the development of lung damage.
https://www.thetimes.co.uk/article/the-flu-and-covid-twindemic-is-coming-how-to-breathe-easily-this-winter-tcw0l0lcc
Year(s) Of Engagement Activity 2021
URL https://www.thetimes.co.uk/article/the-flu-and-covid-twindemic-is-coming-how-to-breathe-easily-this-...
 
Description Wright-Fleming Institute Infection and Immunity seminar St Mary's Hospital Imperial College London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Gave a talk via Teams to researchers entitled 'Understanding Pulmonary Fibrosis in the Post COVID World.' lots of questions and requests for face to face follow-up visits.
Year(s) Of Engagement Activity 2022
 
Description Y12 NHLI Work Experience: Research of Interstitial lung disease & pulmonary fibrosis 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Gave a lecture to sixth form students about how and why we go about trying to cure an incurable disease. Received a lot of questions and it stimulated a lot of debate.
Year(s) Of Engagement Activity 2021