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

Toni M. Delorey, Carly G. K. Ziegler, Graham Heimberg, Rachelly Normand, Yiming Yang, Åsa Segerstolpe, Domenic Abbondanza, Stephen J. Fleming, Ayshwarya Subramanian, Daniel T. Montoro, Karthik A. Jagadeesh, Kushal K. Dey, Pritha Sen, Michal Slyper, Yered H. Pita-Juárez, Devan Phillips, Jana Biermann, Zohar Bloom-Ackermann, Nikolaos Barkas, Andrea Ganna, James Gomez, Johannes C. Melms, Igor Katsyv, Erica Normandin, Pourya Naderi, Yury V. Popov, Siddharth S. Raju, Sebastian Niezen, Linus T.-Y. Tsai, Katherine J. Siddle, Malika Sud, Victoria M. Tran, Shamsudheen K. Vellarikkal, Yiping Wang, Liat Amir-Zilberstein, Deepak S. Atri, Joseph Beechem, Olga R. Brook, Jonathan Chen, Prajan Divakar, Phylicia Dorceus, Jesse M. Engreitz, Adam Essene, Donna M. 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 E. McLoughlin, Eric M. Miller, Christoph Muus, Mari Niemi, Robert Padera, Liuliu Pan, Deepti Pant, Carmel Pe’er, Jenna Pfiffner-Borges, Christopher J. Pinto, Jacob Plaisted, Jason Reeves, Marty Ross, Melissa Rudy, Erroll H. Rueckert, Michelle Siciliano, Alexander Sturm, Ellen Todres, Avinash Waghray, Sarah Warren, Shuting Zhang, Daniel R. Zollinger, Lisa Cosimi, Rajat M. Gupta, Nir Hacohen, Hanina Hibshoosh, Winston Hide, Alkes L. Price, Jayaraj Rajagopal, Purushothama Rao Tata, Stefan Riedel, Gyongyi Szabo, Timothy L. Tickle, Patrick T. Ellinor, Deborah Hung, Pardis C. Sabeti, Richard Novak, Robert Rogers, Donald E. Ingber, Z. Gordon Jiang, Dejan Juric, Mehrtash Babadi, Samouil L. Farhi, Benjamin Izar, James R. Stone, Ioannis S. Vlachos (), Isaac H. Solomon, Orr Ashenberg, Caroline B. M. Porter, Bo Li, Alex K. Shalek (), Alexandra-Chloé Villani (), Orit Rozenblatt-Rosen () and Aviv Regev ()
Additional contact information
Toni M. Delorey: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Carly G. K. Ziegler: Broad Institute of MIT and Harvard
Graham Heimberg: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Rachelly Normand: Broad Institute of MIT and Harvard
Yiming Yang: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Åsa Segerstolpe: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Domenic Abbondanza: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Stephen J. Fleming: Data Sciences Platform, Broad Institute of MIT and Harvard
Ayshwarya Subramanian: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Daniel T. Montoro: Broad Institute of MIT and Harvard
Karthik A. Jagadeesh: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Kushal K. Dey: Harvard T. H. Chan School of Public Health, Harvard University
Pritha Sen: Broad Institute of MIT and Harvard
Michal Slyper: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Yered H. Pita-Juárez: Broad Institute of MIT and Harvard
Devan Phillips: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Jana Biermann: Division of Hematology/Oncology, Columbia University Irving Medical Center
Zohar Bloom-Ackermann: Broad Institute of MIT and Harvard
Nikolaos Barkas: Data Sciences Platform, Broad Institute of MIT and Harvard
Andrea Ganna: Institute for Molecular Medicine Finland
James Gomez: Broad Institute of MIT and Harvard
Johannes C. Melms: Division of Hematology/Oncology, Columbia University Irving Medical Center
Igor Katsyv: Columbia University Irving Medical Center
Erica Normandin: Broad Institute of MIT and Harvard
Pourya Naderi: Harvard Medical School
Yury V. Popov: Harvard Medical School
Siddharth S. Raju: Broad Institute of MIT and Harvard
Sebastian Niezen: Harvard Medical School
Linus T.-Y. Tsai: Broad Institute of MIT and Harvard
Katherine J. Siddle: Broad Institute of MIT and Harvard
Malika Sud: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Victoria M. Tran: Broad Institute of MIT and Harvard
Shamsudheen K. Vellarikkal: Broad Institute of MIT and Harvard
Yiping Wang: Division of Hematology/Oncology, Columbia University Irving Medical Center
Liat Amir-Zilberstein: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Deepak S. Atri: Broad Institute of MIT and Harvard
Joseph Beechem: NanoString Technologies Inc
Olga R. Brook: Beth Israel Deaconess Medical Center
Jonathan Chen: Broad Institute of MIT and Harvard
Prajan Divakar: NanoString Technologies Inc
Phylicia Dorceus: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Jesse M. Engreitz: Broad Institute of MIT and Harvard
Adam Essene: Beth Israel Deaconess Medical Center
Donna M. Fitzgerald: Massachusetts General Hospital
Robin Fropf: NanoString Technologies Inc
Steven Gazal: University of Southern California
Joshua Gould: Klarman Cell Observatory, Broad Institute of MIT and Harvard
John Grzyb: Brigham and Women’s Hospital
Tyler Harvey: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Jonathan Hecht: Harvard Medical School
Tyler Hether: NanoString Technologies Inc
Judit Jané-Valbuena: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Michael Leney-Greene: Broad Institute of MIT and Harvard
Hui Ma: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Cristin McCabe: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Daniel E. McLoughlin: Massachusetts General Hospital
Eric M. Miller: NanoString Technologies Inc
Christoph Muus: Broad Institute of MIT and Harvard
Mari Niemi: Institute for Molecular Medicine Finland
Robert Padera: Brigham and Women’s Hospital
Liuliu Pan: NanoString Technologies Inc
Deepti Pant: Beth Israel Deaconess Medical Center
Carmel Pe’er: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Jenna Pfiffner-Borges: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Christopher J. Pinto: Harvard Medical School
Jacob Plaisted: Brigham and Women’s Hospital
Jason Reeves: NanoString Technologies Inc
Marty Ross: NanoString Technologies Inc
Melissa Rudy: Broad Institute of MIT and Harvard
Erroll H. Rueckert: NanoString Technologies Inc
Michelle Siciliano: Brigham and Women’s Hospital
Alexander Sturm: Broad Institute of MIT and Harvard
Ellen Todres: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Avinash Waghray: Harvard Stem Cell Institute
Sarah Warren: NanoString Technologies Inc
Shuting Zhang: Broad Institute of MIT and Harvard
Daniel R. Zollinger: NanoString Technologies Inc
Lisa Cosimi: Brigham and Women’s Hospital
Rajat M. Gupta: Broad Institute of MIT and Harvard
Nir Hacohen: Broad Institute of MIT and Harvard
Hanina Hibshoosh: Columbia University Irving Medical Center
Winston Hide: Harvard Medical School
Alkes L. Price: Harvard T. H. Chan School of Public Health, Harvard University
Jayaraj Rajagopal: Massachusetts General Hospital
Purushothama Rao Tata: Duke University School of Medicine
Stefan Riedel: Harvard Medical School
Gyongyi Szabo: Broad Institute of MIT and Harvard
Timothy L. Tickle: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Patrick T. Ellinor: Broad Institute of MIT and Harvard
Deborah Hung: Broad Institute of MIT and Harvard
Pardis C. Sabeti: Broad Institute of MIT and Harvard
Richard Novak: Harvard University
Robert Rogers: Beth Israel Deaconess Medical Center
Donald E. Ingber: Harvard University
Z. Gordon Jiang: Harvard Medical School
Dejan Juric: Harvard Medical School
Mehrtash Babadi: Data Sciences Platform, Broad Institute of MIT and Harvard
Samouil L. Farhi: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Benjamin Izar: Division of Hematology/Oncology, Columbia University Irving Medical Center
James R. Stone: Massachusetts General Hospital, Harvard Medical School
Ioannis S. Vlachos: Broad Institute of MIT and Harvard
Isaac H. Solomon: Brigham and Women’s Hospital
Orr Ashenberg: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Caroline B. M. Porter: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Bo Li: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Alex K. Shalek: Broad Institute of MIT and Harvard
Alexandra-Chloé Villani: Broad Institute of MIT and Harvard
Orit Rozenblatt-Rosen: Klarman Cell Observatory, Broad Institute of MIT and Harvard
Aviv Regev: Klarman Cell Observatory, Broad Institute of MIT and Harvard

Nature, 2021, vol. 595, issue 7865, 107-113

Abstract: Abstract COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1–4, 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.

Date: 2021
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Citations: View citations in EconPapers (19)

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DOI: 10.1038/s41586-021-03570-8

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