Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens

Mao, Y.; Chen, Y.; Li, Y.; Ma, L.; Wang, X.; Wang, Q.; He, A.; Liu, X.; Dong, T.; Gao, W.; Xu, Y.; Liu, L.; Ren, L.; Liu, Q.; Zhou, P.; Hu, B.; Zhou, Y.; Tian, R.; Shi, Z.-L.

doi:10.1101/2023.07.14.548971

bioRxiv · 10.1101/2023.07.14.548971

Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens

Mao, Y.·Chen, Y.·Li, Y.·Ma, L.·Wang, X.·Wang, Q.·He, A.·Liu, X.·Dong, T.·Gao, W.·Xu, Y.·Liu, L.·Ren, L.·Liu, Q.·Zhou, P.·Hu, B.·Zhou, Y.·Tian, R.·Shi, Z.-L.

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Abstract

The lung, as a primary target of SARS-CoV-2, exhibits heterogeneous microenvironment accompanied by various histopathological changes following virus infection. However, comprehensive insight into the protein basis of COVID-19-related pulmonary injury with spatial resolution is currently deficient. Here, we generated a region-resolved quantitative proteomic atlas of seven major pathological structures within the lungs of COVID-19 victims by integrating histological examination, laser microdissection, and ultrasensitive proteomic technologies. Over 10,000 proteins were quantified across 71 dissected FFPE post-mortem specimens. By comparison with control samples, we identified a spectrum of COVID-19-induced protein and pathway dysregulations in alveolar epithelium, bronchial epithelium, and pulmonary blood vessels, providing evidence for the proliferation of transitional-state pneumocytes. Additionally, we profiled the region-specific proteomes of hallmark COVID-19 pulmonary injuries, including bronchiole mucus plug, pulmonary fibrosis, airspace inflammation, and hyperplastic alveolar type 2 cells. Bioinformatic analysis revealed the enrichment of cell-type and functional markers in these regions (e.g. enriched TGFBI in fibrotic region). Furthermore, we identified the up-regulation of proteins associated with viral entry, host restriction, and inflammatory response in COVID-19 lungs, such as FURIN and HGF. Collectively, this study provides spatial proteomic insights for understanding COVID-19-caused pulmonary injury, and may serve as a valuable reference for improving therapeutic intervention for severe pneumonia.

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Mao, Y., Chen, Y., Li, Y., Ma, L., Wang, X., Wang, Q., He, A., Liu, X., Dong, T., Gao, W., Xu, Y., Liu, L., Ren, L., Liu, Q., Zhou, P., Hu, B., Zhou, Y., Tian, R., Shi, Z.-L.. 2023-07-17. Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens. https://doi.org/10.1101/2023.07.14.548971

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