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

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 DL CO <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.