Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps.

TitleSystemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps.
Publication TypeJournal Article
Year of Publication2021
AuthorsPark J, Foox J, Hether T, Danko D, Warren S, Kim Y, Reeves J, Butler DJ, Mozsary C, Rosiene J, Shaiber A, Afshinnekoo E, MacKay M, 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 N, Shapira S, Salvatore M, Loda M, Westblade LF, Cushing M, Rennert H, Kriegel AJ, Elemento O, Imielinski M, Borczuk AC, Meydan C, Schwartz RE, Mason CE
Date Published2021 Mar 09

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.

Alternate JournalbioRxiv
PubMed ID33758858
PubMed Central IDPMC7987017
Grant ListR35 GM138152 / GM / NIGMS NIH HHS / United States
Related Faculty: 
Hanna Rennert, Ph.D. Lars Westblade, Ph.D. Massimo Loda, M.D. Melissa Cushing, M.D. Priya Velu, M.D., Ph.D. Steven P. Salvatore, M.D.


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