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

Delorey, Toni M

Ziegler, Carly GK

Heimberg, Graham

Normand, Rachelly

Yang, Yiming

Segerstolpe, Åsa

Abbondanza, Domenic

Fleming, Stephen J

Subramanian, Ayshwarya

Montoro, Daniel T

Jagadeesh, Karthik A

Dey, Kushal K

Sen, Pritha

Slyper, Michal

Pita-Juárez, Yered H

Phillips, Devan

Biermann, Jana

Bloom-Ackermann, Zohar

Barkas, Nikolaos

Ganna, Andrea

Gomez, James

Melms, Johannes C

Katsyv, Igor

Normandin, Erica

Naderi, Pourya

Popov, Yury V

Raju, Siddharth S

Niezen, Sebastian

Tsai, Linus T-Y

Siddle, Katherine J

Sud, Malika

Tran, Victoria M

Vellarikkal, Shamsudheen K

Wang, Yiping

Amir-Zilberstein, Liat

Atri, Deepak S

Beechem, Joseph

Brook, Olga R

Chen, Jonathan

Divakar, Prajan

Dorceus, Phylicia

Engreitz, Jesse M

Essene, Adam

Fitzgerald, Donna M

Fropf, Robin

Gazal, Steven

Gould, Joshua

Grzyb, John

Harvey, Tyler

Hecht, Jonathan

Hether, Tyler

Jané-Valbuena, Judit

Leney-Greene, Michael

Ma, Hui

McCabe, Cristin

McLoughlin, Daniel E

Miller, Eric M

Muus, Christoph

Niemi, Mari

Padera, Robert

Pan, Liuliu

Pant, Deepti

Pe'er, Carmel

Pfiffner-Borges, Jenna

Pinto, Christopher J

Plaisted, Jacob

Reeves, Jason

Ross, Marty

Rudy, Melissa

Rueckert, Erroll H

Siciliano, Michelle

Sturm, Alexander

Todres, Ellen

Waghray, Avinash

Warren, Sarah

Zhang, Shuting

Zollinger, Daniel R

Cosimi, Lisa

Gupta, Rajat M

Hacohen, Nir

Hibshoosh, Hanina

Hide, Winston

Price, Alkes L

Rajagopal, Jayaraj

Tata, Purushothama Rao

Riedel, Stefan

Szabo, Gyongyi

Tickle, Timothy L

Ellinor, Patrick T

Hung, Deborah

Sabeti, Pardis C

Novak, Richard

Rogers, Robert

Ingber, Donald E

Jiang, Z Gordon

Juric, Dejan

Babadi, Mehrtash

Farhi, Samouil L

Izar, Benjamin

Stone, James R

Vlachos, Ioannis S

Solomon, Isaac H

Ashenberg, Orr

Porter, Caroline BM

Li, Bo

Shalek, Alex K

Villani, Alexandra-Chloé

Rozenblatt-Rosen, Orit

Regev, Aviv

2024-02-01T17:56:28Z

2024-02-01T17:56:28Z

2021-07

COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure^1-4, 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.

10.1038/s41586-021-03570-8

0028-0836

1476-4687

https://hdl.handle.net/10161/30076

eng

Springer Science and Business Media LLC

Nature

10.1038/s41586-021-03570-8

https://creativecommons.org/licenses/by-nc/4.0

Myocardium

Liver

Lung

Pulmonary Alveoli

Kidney

Heart

Fibroblasts

Endothelial Cells

Epithelial Cells

Phagocytes

Humans

Inflammation

RNA, Viral

Autopsy

Viral Load

Regeneration

Organ Specificity

Adult

Aged

Aged, 80 and over

Middle Aged

Biological Specimen Banks

Female

Male

Atlases as Topic

Genome-Wide Association Study

Single-Cell Analysis

COVID-19

SARS-CoV-2

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

Journal article

Tata, Purushothama Rao|0000-0003-4837-0337

107

113

7865

Duke

School of Medicine

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Cell Biology

Medicine

Medicine, Pulmonary, Allergy, and Critical Care Medicine

Duke Cancer Institute

Regeneration Next Initiative

Published

595