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

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.

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.