Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients

ABSTRACT Diffuse alveolar damage (DAD) is a histopathological finding associated with severe viral infections, including SARS-CoV-2. However, the mechanisms mediating progression of DAD are poorly understood. Applying protein digital spatial profiling to lung tissue obtained from a cohort of 27 COVID-19 autopsy cases from the UK, we identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246), and VISTA that distinguishes early / exudative DAD from late / organising DAD with good predictive accuracy. These proteins warrant further investigation as potential immunotherapeutic targets to modulate DAD progression and improve patient outcome.