Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID)

Wild, Jim M.; Porter, Joanna C.; Molyneaux, Philip L.; George, Peter M.; Stewart, Iain; Allen, Richard J.; Aul, Raminder; Baillie, J Kenneth; Barratt, Shaney; Beirne, Paul; Bianchi, Stephen; Blaikley, John; Brooke, Jonathan; Chaudhuri, Nazia; Collier, Guilhem; Denneny, Emma; Docherty, Annemarie B; Fabbri, L.; Gibbons, Michael; Gleeson, Fergus; Gooptu, Bibek; Hall, Ian P.; Hanley, Neil A.; Heightman, Melissa; Hillman, Toby; Johnson, Simon R.; Jones, Mark G.; Khan, Fasihul; Lawson, Rod; Mehta, Puja; Mitchell, Jane A.; Platé, Manuela; Poinasamy, Krisnah; Quint, Jennifer; Ortega, Pilar Rivera; Semple, Malcolm G; Simpson, AJ; Smith, Daniel; Spears, Mark; Spencer, Lisa; Stanel, Stefan; Thickett, David; Thompson, A. A. Roger; Walsh, Simon L.F.; Weatherley, Nicholas D; Weeks, Mark E.; Wootton, Dan; Brightling, Chris; Chambers, Rachel C.; Ho, Ling-Pei; Jacob, Joseph; Hanley, Karen Piper; Wain, Louise V.; Jenkins, R Gisli

doi:10.1136/bmjresp-2021-001049

Cited by 34 publications

(36 citation statements)

References 31 publications

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“…Unresolved radiological changes and impaired lung function are important signs suggestive of fibrotic interstitial lung disease, and prospective studies should accurately define the prevalence of post-COVID pulmonary fibrosis. 126 …”

Section: Discussionmentioning

confidence: 99%

Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis

Fabbri

Moss

Khan

et al. 2022

Thorax

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IntroductionPersisting respiratory symptoms in COVID-19 survivors may be related to development of pulmonary fibrosis. We assessed the proportion of chest CT scans and pulmonary function tests consistent with parenchymal lung disease in the follow-up of people hospitalised with COVID-19 and viral pneumonitis.MethodsSystematic review and random effects meta-analysis of proportions using studies of adults hospitalised with SARS-CoV-2, SARS-CoV, MERS-CoV or influenza pneumonia and followed up within 12 months. Searches performed in MEDLINE and Embase. Primary outcomes were proportion of radiological sequelae on CT scans; restrictive impairment; impaired gas transfer. Heterogeneity was explored in meta-regression.ResultsNinety-five studies (98.9% observational) were included in qualitative synthesis, 70 were suitable for meta-analysis including 60 SARS-CoV-2 studies with a median follow-up of 3 months. In SARS-CoV-2, the overall estimated proportion of inflammatory sequelae was 50% during follow-up (0.50; 95% CI 0.41 to 0.58; I2=95%), fibrotic sequelae were estimated in 29% (0.29; 95% CI 0.22 to 0.37; I2=94.1%). Follow-up time was significantly associated with estimates of inflammatory sequelae (−0.036; 95% CI −0.068 to –0.004; p=0.029), associations with fibrotic sequelae did not reach significance (−0.021; 95% CI −0.051 to 0.009; p=0.176). Impaired gas transfer was estimated at 38% of lung function tests (0.38 95% CI 0.32 to 0.44; I2=92.1%), which was greater than restrictive impairment (0.17; 95% CI 0.13 to 0.23; I2=92.5%), neither were associated with follow-up time (p=0.207; p=0.864).DiscussionSequelae consistent with parenchymal lung disease were observed following COVID-19 and other viral pneumonitis. Estimates should be interpreted with caution due to high heterogeneity, differences in study casemix and initial severity.PROSPERO registration numberCRD42020183139.

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Section: Discussionmentioning

confidence: 99%

Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis

Fabbri

Moss

Khan

et al. 2022

Thorax

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“…There have been heterogenous methods to investigate Long COVID, whether qualitative [26][27][28][29][30] or quantitative 7 , or symptom surveys 31 versus cohort studies 4,32 . Most research still focuses on individual organs [33][34][35][36] . The scale of Long COVID burden necessitates action to develop, evaluate and implement evidence-based investigation, treatment and rehabilitation 37 (e.g., STIMULATE-ICP and other studies 4 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-organ impairment and Long COVID: a 1-year prospective, longitudinal cohort study

Dennis¹,

Cuthbertson

Wootton

et al. 2022

Preprint

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ImportanceMulti-organ impairment associated with Long COVID is a significant burden to individuals, populations and health systems, presenting challenges for diagnosis and care provision. Standardised assessment across multiple organs over time is lacking, particularly in non-hospitalised individuals.ObjectiveTo determine the prevalence of organ impairment in Long COVID patients at 6 and at 12 months after initial symptoms and to explore links to clinical presentation.DesignThis was a prospective, longitudinal study in individuals following recovery from acute COVID-19. We assessed symptoms, health status, and multi-organ tissue characterisation and function, using consensus definitions for single and multi-organ impairment. Physiological and biochemical investigations were performed at baseline on all individuals and those with organ impairment were reassessed, including multi-organ MRI, 6 months later.SettingTwo non-acute settings (Oxford and London).Participants536 individuals (mean 45 years, 73% female, 89% white, 32% healthcare workers, 13% acute COVID-19 hospitalisation) completed baseline assessment (median: 6 months post-COVID-19). 331 (62%) with organ impairment or incidental findings had follow up, with reduced symptom burden from baseline (median number of symptoms: 10 and 3, at 6 and 12 months).ExposureSARS-CoV-2 infection 6 months prior to first assessment.Main outcomePrevalence of single and multi-organ impairment at 6 and 12 months post-COVID-19.ResultsExtreme breathlessness (36% and 30%), cognitive dysfunction (50% and 38%) and poor health-related quality of life (EQ-5D-5L<0.7; 55% and 45%) were common at 6 and 12 months, and associated with female gender, younger age and single organ impairment. At baseline, there was fibro-inflammation in the heart (9%), pancreas (9%), kidney (15%) and liver (11%); increased volume in liver (7%), spleen (8%) and kidney (9%); decreased capacity in lungs (2%); and excessive fat deposition in the liver (25%) and pancreas (15%). Single and multi-organ impairment were present in 59% and 23% at baseline, persisting in 59% and 27% at follow-up.Conclusion and RelevanceOrgan impairment was present in 59% of individuals at 6 months post-COVID-19, persisting in 59% of those followed up at 1 year, with implications for symptoms, quality of life and longer-term health, signalling need for prevention and integrated care of Long COVID.Trial RegistrationClinicalTrials.govIdentifier:NCT04369807Key pointsQuestion: What is the prevalence of organ impairment in Long COVID at 6- and 12-months post-COVID-19?Findings: In a prospective study of 536 mainly non-hospitalised individuals, symptom burden decreased, but single organ impairment persisted in 59% at 12 months post-COVID-19.Meaning: Organ impairment in Long COVID has implications for symptoms, quality of life and longer-term health, signalling need for prevention and integrated care of Long COVID.

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“…Primary analyses of the UKILD-Post COVID ILD study will use complete data from hospitalised and non-hospitalised participants to provide updated estimates of Post-COVID ILD at both early and late follow-up, where quantitation of airway disease parameters on radiological imaging is ongoing. [13] The extent of missing data for ILD diagnostic indicators was high at interim analysis, despite this, 6.9% of PHOSP-COVID participants were at risk of Post-COVID ILDam, which requires both CT confirmation and lung function follow-up that were frequently incomplete. Restricting analyses to Tier 2, with less missing data, suggested 9.0% of PHOSP-COVID participants were at risk.…”

Section: Discussionmentioning

confidence: 99%

“…To support clinical and research management, an interim analysis of the UKILD-Post COVID study was planned to estimate ILDam post hospitalisation after a minimum of one thousand participants had completed an early follow-up visit. [13] We present our approach for estimating the extent of suspected Post-COVID ILDam in hospital discharges across the UK, defined here as total lung involvement of reticulations and ground glass opacities >10% on clinically indicated CT.…”

Section: Introductionmentioning

confidence: 99%

Interstitial lung damage following COVID-19 hospitalisation: an interim analysis of the UKILD Post-COVID study

Stewart

Jacob

Gerorge

et al. 2022

Preprint

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Introduction. Shared characteristics between COVID-19 and pulmonary fibrosis, including symptoms, genetic architecture, and circulating biomarkers, suggests interstitial lung disease (ILD) development may be associated with SARS-CoV-2 infection. Methods. The UKILD Post-COVID study planned interim analysis was designed to stratify risk groups and estimate the prevalence of Post-COVID Interstitial Lung Damage (ILDam) using the Post-HOSPitalisation COVID-19 (PHOSP-COVID) Study. Demographics, radiological patterns and missing data were assessed descriptively. Bayes binomial regression was used to estimate the risk ratio of persistent lung damage >10% involvement in linked, clinically indicated CT scans. Indexing thresholds of percent predicted DLco, chest X-ray findings and severity of admission were used to generate risk strata. Number of cases within strata were used to estimate the amount of suspected Post-COVID ILDam. Results. A total 3702 people were included in the UKILD interim cohort, 2406 completed an early follow-up research visit within 240 days of discharge and 1296 had follow-up through routine clinical review. We linked the cohort to 87 clinically indicated CTs with visually scored radiological patterns (median 119 days; interquartile range 83 to 155, max 240), of which 74 people had ILDam. ILDam was associated with abnormal chest X-ray (RR 1.21 95%CrI 1.05; 1.40), percent predicted DLco<80% (RR 1.25 95%CrI 1.00; 1.56) and severe admission (RR 1.27 95%CrI 1.07; 1.55). A risk index based on these features suggested 6.9% of the interim cohort had moderate to very-high risk of Post-COVID ILDam. Comparable radiological patterns were observed in repeat scans >90 days in a subset of participants. Conclusion. These interim data highlight that ILDam was not uncommon in clinically indicated thoracic CT up to 8 months following SARS-CoV-2 hospitalisation. Whether the ILDam will progress to ILD is currently unknown, however health services should radiologically and physiologically monitor individuals who have Post-COVID ILDam risk factors.

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Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID)

Cited by 34 publications

References 31 publications

Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis

Parenchymal lung abnormalities following hospitalisation for COVID-19 and viral pneumonitis: a systematic review and meta-analysis

Multi-organ impairment and Long COVID: a 1-year prospective, longitudinal cohort study

Interstitial lung damage following COVID-19 hospitalisation: an interim analysis of the UKILD Post-COVID study

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