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COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

Toni M Delorey1, Carly G K Ziegler2,3,4,5,6,7, Graham Heimberg1

  • 1Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Nature
|April 29, 2021
PubMed

Insights

This study reveals how SARS-CoV-2 infection remodels lung tissue, causing failed regeneration and impacting other organs like the heart. Understanding these COVID-19 effects is crucial for developing new treatments.

Area of Science:

  • Pathophysiology of severe SARS-CoV-2 infection
  • Organ-specific cellular and molecular responses to COVID-19

Background:

  • Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes COVID-19, leading to acute respiratory distress syndrome and multi-organ failure.
  • The detailed pathophysiology and cellular consequences of SARS-CoV-2 infection across multiple organs remain incompletely understood.

Purpose of the Study:

  • To generate comprehensive single-cell and spatial atlases of autopsy tissues from COVID-19 decedents.
  • To elucidate the cellular and molecular mechanisms underlying organ damage and failed regeneration in severe COVID-19.

Main Methods:

  • Generation of single-cell atlases from lung, kidney, liver, and heart autopsy samples.
  • Creation of spatial atlases for lung tissues.
  • Integrated computational analysis of multi-omic data to identify cellular remodelling and host responses.

Main Results:

  • Identified substantial remodelling in lung epithelial, immune, and stromal compartments, with evidence of failed tissue regeneration.
  • Observed enrichment of viral RNA in specific lung cell types (mononuclear phagocytes, endothelial cells), triggering distinct host responses.
  • Detected transcriptional alterations in heart tissue and mapped cell types/genes associated with COVID-19 severity using genome-wide association studies.

Conclusions:

  • Provides a foundational dataset elucidating the biological effects of severe SARS-CoV-2 infection across multiple organs.
  • Highlights defective alveolar type 2 cell differentiation and progenitor cell expansion as mechanisms of failed lung regeneration.
  • Offers insights into organ-specific damage and host responses, paving the way for novel therapeutic strategies against severe COVID-19.

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