The UK interstitial lung disease long COVID-19 study
| ISRCTN | ISRCTN16650532 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16650532 |
| IRAS number | 297891 |
| ClinicalTrials.gov number | NCT05514522 |
| Secondary identifying numbers | CPMS 50234, IRAS 297891, 21IC6978 |
- Submission date
- 20/09/2021
- Registration date
- 08/12/2021
- Last edited
- 01/05/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
A commonly reported after effect of contracting COVID-19 is developing Post COVID Interstitial Lung Disease (PC-ILD). PC-ILD is inflammation, scarring (fibrosis), or both that can cause permanent lung damage. Inflammation may be reversible but can progress to fibrosis which may worsen over time. The number of people with ILD is not clear but could be high. Highlighting the disease history and risk factors for the development of lung fibrosis could help define better treatment options. This is a study of patients with suspected ILD following COVID-19 to determine the prevalence of ILD at 12 months following infection as well as factors that influence the recovery or worsening of the condition.
Who can participate?
Patients aged 18 to 99 years old with a proven COVID-19 infection who have continued to suffer respiratory (breathing) symptoms prompting further clinical care and a CT scan to determine their lung condition.
What does the study involve?
CT imaging and lung function testing will be performed as part of a routine investigation in the post-COVID clinic. For patients who consent to additional tests, these will be done by a member of the research team at the same clinic. Following assessment of post-COVID patients at baseline (3-6 months after infection), those with clinical and radiological features suggestive of ILD will be included in the study population. A repeat CT will be offered at 12 months (+/- 3 months) after infection. Those with no clinical, radiological or physiological features of ILD will be invited to enrol as part of the control cohort. Participants will also be offered lung function testing at 3 and 12 months and asked to complete questionnaires assessing for breathlessness, fatigue, cognition and quality of life. They will be offered the opportunity to perform a walk test to assess aerobic capacity and further blood tests for genetic testing and further analysis.
What are the possible benefits and risks of participating?
These procedures are purely for research and there will be no direct benefit to participants. However, it is to be hoped that the research will lead to an improved understanding of the causes of lung fibrosis following COVID-19 and the mechanisms by which it occurs. The researchers will collect data from the participants' records, there is minimal risk, and all information will be used anonymously. If participants agree to provide additional samples, being a part of this study means that more samples will be taken than are needed for normal care. Whenever possible these samples will be taken at the same time as regular samples to reduce the extra procedures. All of the things done as part of this research are very safe and happen in the hospital on a daily basis. There is a risk of pain or discomfort when samples are taken. During the study participants will have blood samples taken. This is a standard procedure which is unlikely to cause you any problems but can sometimes cause discomfort. Collecting a blood sample from a vein may cause pain, swelling, bruising, lightheadedness, fainting, and very rarely, clot formation, nerve damage and/or infection at the site of the needle stick. However, all venepuncture and blood sampling will be conducted by a fully phlebotomy trained member of the clinical research team. The researchers will use the samples to try and work out what things contributes to the risk of getting COVID-19, how severe the infection is and how people recover from it. These will be looked at in batches and will not have any details on them about who they belong to, therefore, the researchers will not attempt to identify participants or inform them of any results from the sample testing. Participants and their GPs will not receive individual results from these tests as they are not being used for diagnostic purposes, they are solely for research and safety purposes.
Where is the study run from?
Imperial College London (UK)
When is the study starting and how long is it expected to run for?
March 2021 to March 2027
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
1. Prof. Gisli Jenkins, gisli.jenkins@imperial.ac.uk
2. Dr Valerie Quinn, v.quinn@imperial.ac.uk
Contact information
Scientific
Chief Investigator
National Heart and Lung Institute
Imperial College London
Guy Scadding Building
Cale Street
London
SW3 6LY
United Kingdom
| Phone | +44 (0)207 594 1063 |
|---|---|
| gisli.jenkins@imperial.ac.uk |
Scientific
Project Manager
Imperial College National Heart and Lung Institute
Emmanuel Kay Building
1B Manresa Road
London
SW3 6LR
United Kingdom
| Phone | +44 (0)2075947972 |
|---|---|
| v.quinn@imperial.ac.uk |
Study information
| Study design | Observational; Design type: Clinical Laboratory Study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Clinical laboratory study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | 40449_PIS_V1.0_18May21.pdf |
| Scientific title | The UK Interstitial Lung Disease Long-COVID19 study (UKILD-Long COVID): understanding the burden of interstitial lung disease in long COVID |
| Study acronym | UKILD-Long COVID |
| Study objectives | The primary objective of the study is to determine the prevalence of interstitial lung disease (ILD) at 12 months following SARS-CoV-2 infection and whether clinical severity correlates with the severity of ILD in survivors. |
| Ethics approval(s) | Approved 18/08/2021, London Riverside (Health Research Authority, Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, UK; +44 (0)207 104 8184; christian.bertholle@hra.nhs.uk, riverside.rec@hra.nhs.uk), REC ref: 21/HRA/3313 |
| Health condition(s) or problem(s) studied | COVID-19 (SARS-CoV-2 infection) |
| Intervention | Participants will be required to attend up to three clinic visits over a 12-month period: at three months post initial COVID infection, 6 months and 12 months. Recruitment 1. Participants who have been recruited to the national PHOSP-COVID study have all consented for their data to be used. Similarly, participants of other studies or trials that recruit SARS-CoV-2 infected patients will also be approached. 2. COVID-19 patients attending post-COVID clinics will be identified, and eligibility assessed by review of medical records by the clinical team. They will be provided with an invitation letter and study information. If interested they will be approached by the PC-ILD study team who will supply study information in person or by post or email. Potential participants may be re-contacted on the day of, or up to seven days following, initial contact to discuss any queries they may have and assess eligibility. Screening and Eligibility Assessment Patients will be assessed by the clinical teams for eligibility against the inclusion or exclusion criteria. If they satisfy the inclusion and exclusion criteria of the protocol, they will be invited to participate. Pre-screening for eligibility will take place prior to consent. It will be done by the direct care team using patient notes. There will be no access to patient identifiable data outside of the direct care team prior to consent. Visit 1 This will be at about 3 months post initial infection. The research team will re-review eligibility and obtain written informed consent. They will take a clinical history, perform a brief examination, measure height and weight and calculate body mass index (BMI). Blood samples will be taken, lung function tests performed, and participants will be asked if they would like to undergo a walk test to assess fitness and symptoms of breathlessness. They will be taken through a series of questionnaires assessing quality of life, frailty, personal health, cognition, breathlessness and fatigue. Visit 2 & 3 An optional visit 2 will be at around 6 months after infection and visit 3 will be around 12 months. The assessments described for visit 1 will be repeated. Other investigations Participant consent will be sought to obtain hospital electronic patient records for clinical outcome data and images from the time of infection, hospitalisation and follow up. Controls Individuals who meet the criteria for initial study inclusion (COVID-19 and clinical indication for CT scanning) but have no clinical, radiological or physiological features of ILD will be invited to enrol as part of the control cohort for follow up. Sample size justification This study will recruit 2,000 patients from post-COVID clinics and will run alongside the PHOSP-COVID study which will recruit up to 10,000 participants. Post-COVID related breathlessness has been reported to affect approximately 40% of people hospitalised with severe disease and 10-20% of people who suffered mild COVID-19. Preliminary analysis from UK and international studies have described up to 80% of hospitalised COVID-19 patients have the presence of symptoms, radiology and lung function changes concordant with ILD, depending on the severity of the underlying illness. It is anticipated that approximately 20% (2400/12000) of people recruited into the UKILD-Post COVID study will have features consistent with ILD for characterisation, which will provide a sufficient sample size for descriptive analysis, evaluation of incidence and prevalence, and assessment of risk factors. Planned Interim Analyses A planned interim will be performed after the 3-month follow up of the first 100 participants to provide initial insights into expected radiological patterns and to preliminarily describe the potential PC-ILD burden for the support of clinical management. A second planned interim will be performed at 6 months to inform recruitment to study. Patient and Public Involvement Action for Pulmonary Fibrosis charity and patient partners have been involved from the conception of this study to inform study design and conduct. They will also form part of the ongoing steering committee appraising patient-facing material and facilitating the dissemination of findings to IPF patients and their families. |
| Intervention type | Other |
| Primary outcome measure | Multi-disciplinary team (MDT) confirmed diagnosis of ILD at 12 months (+/- 3 months) after acute infection |
| Secondary outcome measures | 1. Lung function decline ≥10% OR worsening extent of ILD on CT scan using image analysis or MDT discussion at 3 and 12 months (+/- 3 months) after acute infection 2. Resolution of ILD: any of the following: ≥10% relative improvement in FVC, DLco, or reduction of radiological extent at 12 months (+/- 3 months) post SARS-CoV-2 3. Persistence of ILD in those not meeting the definition of progression or resolution at 12 months (+/- 3 months) post SARS-CoV-2 4. Persistence of ILAs measured using Computerised Tomography at 12 months (+/- 3 months) post SARS-CoV-2 5. Markers of severity of acute infection (e.g. CRP) measured using initial clinical assessment at 12 months (+/- 3 months) post SARS-CoV-2 6. Medical therapy used for acute infection measured using clinical records at 12 months (+/- 3 months) post SARS-CoV-2 7. Breathlessness measured using the Medical Research Council dyspnoea scale, Dyspnoea 12 at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection 8. Fatigue measured using FACIT-F at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection 9. Cognition measured using the Montreal Cognition Assessment (MOCA) at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection 10. Quality of life measured using Short Form-36 (SF-36), EQ5D-5L at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection 11. Impact of COVID19 on aerobic capacity and endurance measured using the incremental shuttle walk test or cardiopulmonary exercise test, if clinically indicated, at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection Exploratory: 1. Exploratory circulating biomarkers measured using whole blood RNA sequencing (including peripheral blood mononuclear cells) and analysis of epigenetic modifications and proteomics at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection 2. Serological and cellular measures of epithelial and endothelial injury and thrombosis measured using serum biomarkers of epithelial and endothelial injury, NETosis and thrombosis, cellular measurements, and serum/plasma Nordic biomarkers, LRG-1, MMP-7 etc; NETs at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection 3. Genetic risk factors for lung fibrosis and radiological progression, continuously and dichotomised, assessed using genome-wide array genotyping, genetic testing from blood/saliva of putative candidate genes, and use of genomic data and telomere length in a subset at no sooner than the 3-month visit 4. Laboratory parameters (including CRP, FBC) and extent of ILD in patients measured using blood and serum analysis at 3 months, 6 months (+/- 6 weeks) and 12 months (+/- 3 months) post SARS-CoV-2 infection |
| Overall study start date | 12/03/2021 |
| Completion date | 31/03/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 2000; UK Sample Size: 2000 |
| Total final enrolment | 183 |
| Key inclusion criteria | 1. Aged 18 to 99 years old 2. Evidence of SARS-CoV-2 infection confirmed by PCR or serology 3 months (+/- 6 weeks) earlier 3. Clinical indication for a chest CT scan as per clinician judgment 4. Participants who have been identified and consented for the main PHOS-PCOVID study are also eligible to join this study 5. Allow inclusion of patients who are receiving up to 10 mg of prednisolone a day |
| Key exclusion criteria | 1. Life-limiting illness within 12 months 2. Significant pre-existing lung disease prior to March 2020, which in the investigator’s judgement could make the chest CT scans difficult to interpret |
| Date of first enrolment | 18/08/2021 |
| Date of final enrolment | 24/02/2023 |
Locations
Countries of recruitment
- United Kingdom
Study participating centres
London
NW1 2PG
United Kingdom
London
SW3 6NP
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Oxford Road
Manchester
M13 9PL
United Kingdom
Guy Scadding Building
London
SW3 6LY
United Kingdom
Department of Molecular and Cell Biology
Lancaster Road
Leicester
LE1 7RH
United Kingdom
School of Medicine
Division of Respiratory Medicine
Nottingham
NG7 2RD
United Kingdom
Oxford Road
Manchester
M13 9PL
United Kingdom
Faculty of Medical Sciences
Gower Street
London
WC1E 6BT
United Kingdom
London
W2 1BL
United Kingdom
University Road
Southampton
SO17 1BJ
United Kingdom
Liverpool
L69 3BX
United Kingdom
Western Bank
Sheffield
S10 2TN
United Kingdom
Nuffield, Henry Wellcome Building for Molecular Physiology
Old Road Campus
Headington
Oxford
OX3 7BN
United Kingdom
Sponsor information
University/education
c/o Cheuk Fung Wong
Room 221, Level 2, Medical School Building
Norfolk Place
London
W2 1PG
England
United Kingdom
| Phone | +44 (0)2075949832 |
|---|---|
| cheuk-fung.wong@imperial.ac.uk | |
| Website | http://www.imperial.ac.uk/ |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The final results of the study will be disseminated in the form of a manuscript/s in a peer-reviewed scientific journal, presented at national and international conferences and in local meetings. In addition, where relevant, data from potential interim analyses will be presented at (a) relevant congress (es). In addition, the study database will be made available for future research. |
| IPD sharing plan | The PHOSP COVID study (ISRCTN10980107) is a national consortium that provides a platform to study the long-term consequences of COVID19 hospitalisations. The study described here will aim to recruit a further 2000 individuals with proven COVID-19 who were not hospitalised but presented to Long-COVID clinics with persistent respiratory symptoms such as breathlessness or cough and are referred for cross-sectional imaging (computer tomography, CT) at baseline (3 months weeks after their first COVID-19 symptoms). Data from both studies will be collated and stored in a REDCAP study database available for future research. Data will be shared within a TRE at Edinburgh university. Currently both studies are continuing to build and amass data so the data is not wholly available for other research. Once the database is completed, details and availability will be clarified. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.0 | 18/05/2021 | 02/11/2021 | No | Yes |
| Protocol article | 01/09/2021 | 02/11/2021 | Yes | No | |
| Protocol file | version 1.2 | 28/08/2021 | 02/11/2021 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
01/05/2025: The overall trial end date was changed from 31/03/2023 to 31/03/2027.
20/03/2023: The following changes were made to the trial record:
1. The recruitment end date was changed from 16/08/2022 to 24/02/2023.
2. The overall trial end date was changed from 31/03/2023 to 31/03/2023.
3. Total final enrolment added.
20/03/2023: The ClinicalTrials.gov number was added.
23/08/2022: The contact was updated.
17/08/2022: The overall trial end date has been changed from 31/08/2022 to 31/03/2023 and the plain English summary updated accordingly.
20/09/2021: Trial's existence confirmed by the NIHR.
