Faculty Collaboration Database

System-wide transcriptome damage and tissue identity loss in COVID-19 patients. Cell Rep Med 2022 Feb 15;3(2):100522

Date

03/03/2022

Pubmed ID

35233546

Pubmed Central ID

PMC8784611

DOI

10.1016/j.xcrm.2022.100522

Scopus ID

2-s2.0-85124273639 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections.

Author List

Park J, Foox J, Hether T, Danko DC, Warren S, Kim Y, Reeves J, Butler DJ, Mozsary C, Rosiene J, Shaiber A, Afshin EE, MacKay M, Rendeiro AF, Bram Y, Chandar V, Geiger H, Craney A, Velu P, Melnick AM, Hajirasouliha I, Beheshti A, Taylor D, Saravia-Butler A, Singh U, Wurtele ES, Schisler J, Fennessey S, Corvelo A, Zody MC, Germer S, Salvatore S, Levy S, Wu S, Tatonetti NP, Shapira S, Salvatore M, Westblade LF, Cushing M, Rennert H, Kriegel AJ, Elemento O, Imielinski M, Rice CM, Borczuk AC, Meydan C, Schwartz RE, Mason CE

Author

Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Case-Control Studies
Cohort Studies
Female
Gene Expression Regulation
Humans
Influenza, Human
Lung
Male
Middle Aged
Orthomyxoviridae
Transcriptome
Viral Load