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

Abstract

The molecular mechanisms underlying the clinical manifestations of COVID-19 and what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome, remains 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 this 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 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.

SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery

“…S2A to C).These data were also cross-referenced to matching tissues derived from human cadaver specimens that were infected with COVID-19 at the time of death, as described elsewhere ( Fig. 2C ) ( 41 ). These comparisons encompassed more than 50 samples at both early and late time points, which clustered based on tissues from which they derived (fig.…”

Targeted Down Regulation Of Core Mitochondrial Genes During SARS-CoV-2 Infection

“…The autopsy samples from 35 deceased COVID-19 patients encompassing high and low SARS-CoV-2 levels were compared to five uninfected controls. Samples were collected from the heart, kidney, liver, lung, and lymph nodes ( 44 ). We also included publicly available RNA-seq data on monocytes from COVID-19 patients ( 45 ).…”

“…RNA isolation and library preparation is detailed in Park, et al( 2 ). Briefly, autopsy tissues were collected from lung, liver, lymph nodes, kidney, and heart and were placed directly into Trizol, homogenized and then snap frozen in liquid nitrogen.…”

“…The full methods of the patient sample collection from the autopsy patients are currently available in the Park et al ( 2 ). All autopsies are performed with the consent of the next of kin and permission for retention and research use of tissue.…”

“…The full methods for the analysis of autopsy patients can be found in the Park et al ( 2 ). Briefly, RNA-seq data was processed through the nf-core/rnaseq pipeline ( 9 ).…”