Residual lung abnormality following COVID-19 hospitalisation is characterised by biomarkers of epithelial injury

TY - JOUR

T1 - Residual lung abnormality following COVID-19 hospitalisation is characterised by biomarkers of epithelial injury

AU - Stewart, Iain

AU - Jacob, Joseph

AU - Porter, Joanna C.

AU - Liu, Bin

AU - Tatler, Amanda L.

AU - Gomez, Nancy

AU - Pugh, Matthew R.

AU - John, Alison E.

AU - Allen, Richard J.

AU - Blaikley, John F.

AU - Chaudhuri, Nazia

AU - Denneny, Emma

AU - Fabbri, Laura

AU - George, Peter M.

AU - Guillen-Guio, Beatriz

AU - Gooptu, Bibek

AU - Hall, Ian P.

AU - Ho, Ling Pei

AU - Jarrold, Ian

AU - Johnson, Simon

AU - Jones, Mark G.

AU - Khan, Fasihul

AU - Mehta, Puja

AU - Mitchell, Jane

AU - Molyneaux, Philip L.

AU - Pearl, John E.

AU - Piper Hanley, Karen

AU - Platé, Manuela

AU - Quinn, Valerie

AU - Rivera-Ortega, Pilar

AU - Saunders, Laura C.

AU - Smith, David J.F.

AU - Spears, Mark

AU - Spencer, Lisa G.

AU - Stanel, Stefan C.

AU - Thompson, A. A.Roger

AU - Walsh, Simon

AU - Wild, Jim M.

AU - Wootton, Dan G.

AU - Docherty, Annemarie B.

AU - Gleeson, Fergus

AU - Greenhalf, William

AU - Harrison, Ewen M.

AU - Lone, Nazir

AU - Quint, Jennifer

AU - Maslova, Anastasia

AU - Pohl, Moritz

AU - Young, Simon

AU - Richardson, Matthew

AU - Chalmers, James D.

N1 - Publisher Copyright: © 2026 The Author(s)

PY - 2026/2

Y1 - 2026/2

N2 - 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).

AB - 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).

KW - Biomarker

KW - COVID-19

KW - Epithelial

KW - Hospitalisation

KW - Lung injury

UR - https://www.scopus.com/pages/publications/105028505256

U2 - 10.1016/j.ebiom.2026.106134

DO - 10.1016/j.ebiom.2026.106134

M3 - Article

C2 - 41581494

AN - SCOPUS:105028505256

SN - 2352-3964

VL - 124

JO - EBioMedicine

JF - EBioMedicine

M1 - 106134

ER -