Residual lung abnormality following COVID-19 hospitalisation is characterised by biomarkers of epithelial injury.
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Stewart Iain, Jacob Joseph, Porter Joanna C, Liu Bin, Tatler Amanda L, Gomez Nancy, Pugh Matthew R, John Alison E, Allen Richard J, Blaikley John F, Chaudhuri Nazia, Denneny Emma, Fabbri Laura, George Peter M, Guillen-Guio Beatriz, Gooptu Bibek, Hall Ian P, Ho Ling Pei, Jarrold Ian, Johnson Simon, Jones Mark G, Khan Fasihul, Mehta Puja, Mitchell Jane, Molyneaux Philip L, Pearl John E, Piper Hanley Karen, Platé Manuela, Quinn Valerie, Rivera-Ortega Pilar, Saunders Laura C, Smith David J F, Spears Mark, Spencer Lisa G, Stanel Stefan C, Thompson A A Roger, Walsh Simon, Wild Jim M, Wootton Dan G, Docherty Annemarie B, Gleeson Fergus, Greenhalf William, Harrison Ewen M, Lone Nazir, Quint Jennifer, Maslova Anastasia, Pohl Moritz, Stephens Adam, Young Simon, Singapuri Amisha, Shikotra Aarti, Sereno Marco, Saunders Ruth M, Richardson Matthew, Raman Betty, Poinasamy Krisnah, McAuley Hamish J C, Marks Michael, Leavy Olivia C, Houchen-Wolloff Linzy, Horsley Alex, Harris Victoria C, Greening Neil, Evans Rachael A, Elneima Omer, Chalmers James D, Brightling Christopher E, Chambers Rachel C, Wain Louise V, Jenkins R Gisli, PHOSP-COVID Collaborative Group and the UKILD Consortium
Аннотация
METHODS: Plasma was sampled from the observational Post HOSPitalisation-COVID cohort at five months post-hospitalisation. Epithelial injury biomarkers Krebs von den Lungen-6 (KL-6), matrix metalloproteinase 7 (MMP-7), surfactant protein-D (SP-D) and surfactant protein-A (SP-A) were assayed. In those without follow-up CT, RLA at-risk was defined by percent predicted DLCO <80% and/or abnormal chest X-ray, otherwise they were considered low-risk. Follow-up CT RLA was defined as combined involvement of ground glass opacity and reticulation ≥10%.
FINDINGS: A total of 957 people were included, 846 people with no CT (at-risk n = 103; 12.2%), 111 people with follow-up CT (RLA ≥10% n = 85; 76.6%). All epithelial injury biomarkers were significantly elevated in people at-risk of RLA compared with low-risk. KL-6 and MMP-7 were significantly higher in people with ≥10% RLA than those with <10%, SP-D and SP-A did not reach significance. SP-D and SP-A were associated with percent involvement of reticulation (3.22%, 95% CI 1.19-5.24; 3.03%, 95% CI 0.76-5.30, respectively).
INTERPRETATION: RLA after acute COVID-19 infection were consistent with elevated epithelial injury biomarkers and pro-fibrotic signalling. Future studies should address the temporal association between fibrotic biomarkers and resolution or progression of radiological involvement.
FUNDING: MRC-UK Research and Innovation and National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19 (MR/V027859/1; COV0319; MR/W006111/1).