Residual lung abnormality following COVID-19 hospitalisation is characterised by biomarkers of epithelial injury.
Stewart I., Jacob J., Porter JC., Liu B., Tatler AL., Gomez N., Pugh MR., John AE., Allen RJ., Blaikley JF., Chaudhuri N., Denneny E., Fabbri L., George PM., Guillen-Guio B., Gooptu B., Hall IP., Ho LP., Jarrold I., Johnson S., Jones MG., Khan F., Mehta P., Mitchell J., Molyneaux PL., Pearl JE., Piper Hanley K., Platé M., Quinn V., Rivera-Ortega P., Saunders LC., Smith DJF., Spears M., Spencer LG., Stanel SC., Thompson AAR., Walsh S., Wild JM., Wootton DG., Docherty AB., Gleeson F., Greenhalf W., Harrison EM., Lone N., Quint J., Maslova A., Pohl M., Stephens A., Young S., Singapuri A., Shikotra A., Sereno M., Saunders RM., Richardson M., Raman B., Poinasamy K., McAuley HJC., Marks M., Leavy OC., Houchen-Wolloff L., Horsley A., Harris VC., Greening N., Evans RA., Elneima O., Chalmers JD., Brightling CE., Chambers RC., Wain LV., Jenkins RG., PHOSP-COVID Collaborative Group and the UKILD Consortium .
BACKGROUND: Long term respiratory symptoms are reported following recovery of acute COVID-19 infection and residual lung abnormalities (RLA) on follow-up thoracic computed tomography (CT) after COVID-19 hospitalisation have been observed. It is unknown whether RLA are associated with epithelial lung injury. 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).