Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury.

Deep spatial proteomics reveals region-specific features of severe COVID-19-related pulmonary injury.

Publication date: Jan 18, 2024

As a primary target of severe acute respiratory syndrome coronavirus 2, lung exhibits heterogeneous histopathological changes following infection. However, comprehensive insight into their protein basis with spatial resolution remains deficient, which hinders further understanding of coronavirus disease 2019 (COVID-19)-related pulmonary injury. Here, we generate a region-resolved proteomic atlas of hallmark pathological pulmonary structures by integrating histological examination, laser microdissection, and ultrasensitive proteomics. Over 10,000 proteins are quantified across 71 post-mortem specimens. We identify a spectrum of pathway dysregulations in alveolar epithelium, bronchial epithelium, and blood vessels compared with non-COVID-19 controls, providing evidence for transitional-state pneumocyte hyperplasia. Additionally, our data reveal the region-specific enrichment of functional markers in bronchiole mucus plugs, pulmonary fibrosis, airspace inflammation, and alveolar type 2 cells, uncovering their distinctive features. Furthermore, we detect increased protein expression associated with viral entry and inflammatory response across multiple regions, suggesting potential therapeutic targets. Collectively, this study provides a distinct perspective for deciphering COVID-19-caused pulmonary dysfunction by spatial proteomics.

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Concepts Keywords
Coronavirus CP: Microbiology
Histopathological
Laser
Pulmonary

Semantics

Type Source Name
disease MESH COVID-19
disease MESH pulmonary injury
disease VO Severe acute respiratory syndrome coronavirus 2
disease MESH infection
disease MESH hyperplasia
disease MESH pulmonary fibrosis
disease MESH inflammation

Original Article

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