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

Nature
Authors
Toni Delorey
Carly Ziegler
Graham Heimberg
Rachelly Normand
Yiming Yang
Åsa Segerstolpe
Domenic Abbondanza
Stephen Fleming
Ayshwarya Subramanian
Daniel Montoro
Karthik Jagadeesh
Kushal Dey
Pritha Sen
Michal Slyper
Yered Pita-Juárez
Devan Phillips
Jana Biermann
Zohar Bloom-Ackermann
Nikolaos Barkas
Andrea Ganna
James Gomez
Johannes Melms
Igor Katsyv
Erica Normandin
Pourya Naderi
Yury Popov
Siddharth Raju
Sebastian Niezen
Linus Tsai
Katherine Siddle
Malika Sud
Victoria Tran
Shamsudheen Vellarikkal
Yiping Wang
Liat Amir-Zilberstein
Deepak Atri
Joseph Beechem
Olga Brook
Jonathan Chen
Prajan Divakar
Phylicia Dorceus
Jesse Engreitz
Adam Essene
Donna Fitzgerald
Robin Fropf
Steven Gazal
Joshua Gould
John Grzyb
Tyler Harvey
Jonathan Hecht
Tyler Hether
Judit Jané-Valbuena
Michael Leney-Greene
Hui Ma
Cristin McCabe
Daniel McLoughlin
Eric Miller
Christoph Muus
Mari Niemi
Robert Padera
Liuliu Pan
Deepti Pant
Carmel Pe'er
Jenna Pfiffner-Borges
Christopher Pinto
Jacob Plaisted
Jason Reeves
Marty Ross
Melissa Rudy
Erroll Rueckert
Michelle Siciliano
Alexander Sturm
Ellen Todres
Avinash Waghray
Sarah Warren
Shuting Zhang
Daniel Zollinger
Lisa Cosimi
Rajat Gupta
Nir Hacohen
Hanina Hibshoosh
Winston Hide
Alkes Price
Jayaraj Rajagopal
Purushothama Tata
Stefan Riedel
Gyongyi Szabo
Timothy Tickle
Patrick Ellinor
Deborah Hung
Pardis Sabeti
Richard Novak
Robert Rogers
Donald Ingber
Z Gordon Jiang
Dejan Juric
Mehrtash Babadi
Samouil Farhi
Benjamin Izar
James Stone
Ioannis Vlachos
Isaac Solomon
Orr Ashenberg
Caroline Porter
Bo Li
Alex Shalek
Alexandra-Chloé Villani
Orit Rozenblatt-Rosen
Aviv Regev
Keywords
Female
Humans
Male
Adult
Aged
Middle Aged
Organ Specificity
Fibroblasts
Genome-Wide Association Study
Single-Cell Analysis
Liver
Aged, 80 and over
Inflammation
Kidney
Myocardium
Lung
Endothelial Cells
Regeneration
Epithelial Cells
RNA, Viral
Heart
Viral Load
Autopsy
Biological Specimen Banks
Phagocytes
Atlases as Topic
Pulmonary Alveoli
COVID-19
SARS-CoV-2
Abstract

COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63 intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments.
Year of Publication
2021
Journal
Nature
Volume
595
Issue
7865
Pages
107-113
Date Published
2021 07
ISSN
1476-4687
DOI
10.1038/s41586-021-03570-8
PubMed ID
33915569
PubMed Central ID
PMC8919505
Links
Grant list
WT_ / Wellcome Trust / United Kingdom
R37 MH107649 / MH / NIMH NIH HHS / United States
K08 CA222663 / CA / NCI NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States
P30 DK046200 / DK / NIDDK NIH HHS / United States
P30 CA013696 / CA / NCI NIH HHS / United States
R01 MH107649 / MH / NIMH NIH HHS / United States
R01 MH101244 / MH / NIMH NIH HHS / United States
R37 CA258829 / CA / NCI NIH HHS / United States
U54 CA225088 / CA / NCI NIH HHS / United States
U01 AA026933 / AA / NIAAA NIH HHS / United States
R01 AA020744 / AA / NIAAA NIH HHS / United States
U01 HG009379 / HG / NHGRI NIH HHS / United States
DP2 CA247831 / CA / NCI NIH HHS / United States

Recent Broad Publications