Transcriptional and proteomic insights into the host response in fatal COVID-19 cases.

Published

Journal Article

Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.

Full Text

Duke Authors

Cited Authors

  • Wu, M; Chen, Y; Xia, H; Wang, C; Tan, CY; Cai, X; Liu, Y; Ji, F; Xiong, P; Liu, R; Guan, Y; Duan, Y; Kuang, D; Xu, S; Cai, H; Xia, Q; Yang, D; Wang, M-W; Chiu, IM; Cheng, C; Ahern, PP; Liu, L; Wang, G; Surana, NK; Xia, T; Kasper, DL

Published Date

  • November 10, 2020

Published In

Volume / Issue

  • 117 / 45

Start / End Page

  • 28336 - 28343

PubMed ID

  • 33082228

Pubmed Central ID

  • 33082228

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.2018030117

Language

  • eng

Conference Location

  • United States