The UK Interstitial Lung Disease Long-COVID19 Study (UKILD-Long COVID): Understanding the Burden of Interstitial Lung Disease in Long COVID.

Given the large number of patients infected with SARS-CoV-2, it is vital that the extent of PC-ILD is determined; its natural history defined particularly whether it is time-limited inflammation and reversible, or develops into persistent, or even progressive, fibrosis. Determining the natural history of PC-ILD, and risk factors as well as biomarkers related to outcome such as disease progression, will enable a precise approach to treatments such as immunomodulation or antifibrotic therapy [6], stratification into clinical trials, prognostication and appropriate service provision. This will facilitate assessment and prioritisation of both conventional and novel therapies used in the treatment of COVID-19 during the acute phase to mitigate the subsequent development of PC-ILD. By exploring the long-term implications of SARS-CoV-2 infection across the full spectrum of COVID-19 disease ranging from non-hospitalised patients managed in the community with mild symptoms to those requiring mechanical ventilation, we will define the risk factors for PC-ILD including disease severity, host genetic factors and the effects of antiviral and immunomodulatory treatment administered during the acute phase of the illness. The UKILD Post COVID study is a prospective multicentre observational cohort study that will be managed through the Imperial College National Heart and Lung Institute and funded by the UKRI Medical Research Council and an NIHR professorship (RGJ).

The PHOSP COVID study (ISRCTN10980107) is a national consortium that provides a platform to study the long-term consequences of COVID19 hospitalisations [18]. An expected 10,000 individuals hospitalised by COVID-19 are to be included in baseline assessments after testing positive on PCR for SARS-C0V-2 and will be recruited through the PHOSP platform. 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) [19]. A total of up to 12,000 people will be assessed for longitudinal follow up into the UKILD-Post COVID study. Following assessment of Post COVID patients at baseline (~3-6 months post infection as defined above), those with clinical and radiological features suggestive of ILD will be included into the UKILD-Post COVID study population. Where there are contraindications for CT and if clinically indicated, participants will be eligible for a research-guided 3D ultrashort echo time (UTE) proton MRI as a surrogate for CT. Where individuals meet criteria for initial study inclusion (COVID-19 and clinical indication for CT scanning) but have no clinical, radiological or physiological features of ILD they will be invited to enroll as part of the control cohort for follow up.

This protocol details the research partnership between Imperial (BREATHE Respiratory hub partner), and partner organizations.

2 STUDY OBJECTIVES

2.1 Primary objective The primary objective of the study is to determine the prevalence of ILD at 12 months following SARS-CoV-2 infection and whether clinical severity correlates with severity of ILD in survivors.