System-wide transcriptome damage and tissue identity loss in COVID-19 patients.

TitleSystem-wide transcriptome damage and tissue identity loss in COVID-19 patients.
Publication TypeJournal Article
Year of Publication2022
AuthorsPark 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 ESyrkin, 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
JournalCell Rep Med
Date Published2022 Feb 15
KeywordsAdult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, COVID-19, Female, Gene Expression Regulation, Humans, Influenza, Human, Lung, Male, Middle Aged, Orthomyxoviridae, Respiratory Distress Syndrome, RNA-Seq, SARS-CoV-2, Transcriptome, Viral Load

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.

Alternate JournalCell Rep Med
PubMed ID35233546
PubMed Central IDPMC8784611
Grant ListU01 DA053941 / DA / NIDA NIH HHS / United States
R01 AI151059 / AI / NIAID NIH HHS / United States
T32 CA203702 / CA / NCI NIH HHS / United States
R21 AI129851 / AI / NIAID NIH HHS / United States
R01 CA249054 / CA / NCI NIH HHS / United States
R01 CA234614 / CA / NCI NIH HHS / United States
P01 CA214274 / CA / NCI NIH HHS / United States
R35 GM138152 / GM / NIGMS NIH HHS / United States
Related Faculty: 
Lars Westblade, Ph.D. Hanna Rennert, Ph.D. Melissa Cushing, M.D. Steven P. Salvatore, M.D.


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