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

Date
2021-03-09
Authors
Park, Jiwoon
Foox, Jonathan
Hether, Tyler
Beheshti, Afshin
Saravia-Butler, Amanda
Singh, Urminder
Wurtele, Eve
Journal Title
Journal ISSN
Volume Title
Publisher
Altmetrics
Authors
Research Projects
Organizational Units
Journal Issue
Series
Abstract

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.

Description

This preprint is made available through bioRxiv, doi:10.1101/2021.03.08.434433.

Keywords
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spatial transcriptomics, coronavirus disease 2019 (COVID-19), next-generation sequencing (NGS), RNA-seq, host response
Citation
DOI
Collections