Transcriptional and Proteomic Insights into the Host Response in Fatal COVID-19 Cases

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2020 Oct 21

PMID 33082228

Citations 113

Authors

Meng Wu

Yaobing Chen

Han Xia

Changli Wang

Chin Yee Tan

Xunhui Cai

Yufeng Liu

Fenghu Ji

Peng Xiong

Ran Liu

Yuanlin Guan

Yaqi Duan

Dong Kuang

Sanpeng Xu

Hanghang Cai

Qin Xia

Dehua Yang

Ming-Wei Wang

Isaac M Chiu

Chao Cheng

Philip P Ahern

Liang Liu

Guoping Wang

Neeraj K Surana

Tian Xia

Dennis L Kasper

Affiliations

Soon will be listed here.

Abstract

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.

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