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, ��sa Segerstolpe, Domenic Abbondanza, Stephen J Fleming, Ayshwarya Subramanian, Daniel T Montoro, Karthik A Jagadeesh, Kushal K Dey, Pritha Sen, Michal Slyper, Yered H Pita-Ju��rez, 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 Jan��-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-Chlo�� Villani, Orit Rozenblatt-Rosen, Aviv Regev
Author Information
Toni M Delorey: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Carly G K Ziegler: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Graham Heimberg: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Rachelly Normand: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yiming Yang: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
��sa Segerstolpe: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Domenic Abbondanza: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Stephen J Fleming: Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Ayshwarya Subramanian: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Daniel T Montoro: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Karthik A Jagadeesh: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Kushal K Dey: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
Pritha Sen: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Michal Slyper: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yered H Pita-Ju��rez: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Devan Phillips: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jana Biermann: Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA. ORCID
Zohar Bloom-Ackermann: Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nikolaos Barkas: Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Andrea Ganna: Institute for Molecular Medicine Finland, Helsinki, Finland.
James Gomez: Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Johannes C Melms: Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA. ORCID
Igor Katsyv: Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Erica Normandin: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pourya Naderi: Harvard Medical School, Boston, MA, USA.
Yury V Popov: Harvard Medical School, Boston, MA, USA.
Siddharth S Raju: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sebastian Niezen: Harvard Medical School, Boston, MA, USA. ORCID
Linus T-Y Tsai: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Katherine J Siddle: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Malika Sud: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Victoria M Tran: Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Shamsudheen K Vellarikkal: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yiping Wang: Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Liat Amir-Zilberstein: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Deepak S Atri: Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Joseph Beechem: NanoString Technologies Inc, Seattle, WA, USA.
Olga R Brook: Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA. ORCID
Jonathan Chen: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Prajan Divakar: NanoString Technologies Inc, Seattle, WA, USA.
Phylicia Dorceus: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jesse M Engreitz: Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Adam Essene: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Donna M Fitzgerald: Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Robin Fropf: NanoString Technologies Inc, Seattle, WA, USA.
Steven Gazal: Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Joshua Gould: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
John Grzyb: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Tyler Harvey: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jonathan Hecht: Harvard Medical School, Boston, MA, USA.
Tyler Hether: NanoString Technologies Inc, Seattle, WA, USA.
Judit Jan��-Valbuena: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael Leney-Greene: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hui Ma: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cristin McCabe: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Daniel E McLoughlin: Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Eric M Miller: NanoString Technologies Inc, Seattle, WA, USA. ORCID
Christoph Muus: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Mari Niemi: Institute for Molecular Medicine Finland, Helsinki, Finland.
Robert Padera: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Liuliu Pan: NanoString Technologies Inc, Seattle, WA, USA.
Deepti Pant: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Carmel Pe'er: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jenna Pfiffner-Borges: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Christopher J Pinto: Department of Medicine, Harvard Medical School, Boston, MA, USA.
Jacob Plaisted: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Jason Reeves: NanoString Technologies Inc, Seattle, WA, USA.
Marty Ross: NanoString Technologies Inc, Seattle, WA, USA.
Melissa Rudy: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Erroll H Rueckert: NanoString Technologies Inc, Seattle, WA, USA.
Michelle Siciliano: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Alexander Sturm: Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ellen Todres: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Avinash Waghray: Harvard Stem Cell Institute, Cambridge, MA, USA.
Sarah Warren: NanoString Technologies Inc, Seattle, WA, USA.
Shuting Zhang: Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Daniel R Zollinger: NanoString Technologies Inc, Seattle, WA, USA.
Lisa Cosimi: Infectious Diseases Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Rajat M Gupta: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nir Hacohen: Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Hanina Hibshoosh: Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.
Winston Hide: Harvard Medical School, Boston, MA, USA.
Alkes L Price: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA. ORCID
Jayaraj Rajagopal: Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Purushothama Rao Tata: Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA. ORCID
Stefan Riedel: Harvard Medical School, Boston, MA, USA. ORCID
Gyongyi Szabo: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Timothy L Tickle: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Patrick T Ellinor: Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Deborah Hung: Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pardis C Sabeti: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Richard Novak: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. ORCID
Robert Rogers: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Donald E Ingber: John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. ORCID
Z Gordon Jiang: Harvard Medical School, Boston, MA, USA.
Dejan Juric: Department of Medicine, Harvard Medical School, Boston, MA, USA. ORCID
Mehrtash Babadi: Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Samouil L Farhi: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Benjamin Izar: Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA. ORCID
James R Stone: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ioannis S Vlachos: Broad Institute of MIT and Harvard, Cambridge, MA, USA. ivlachos@bidmc.harvard.edu. ORCID
Isaac H Solomon: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. ORCID
Orr Ashenberg: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Caroline B M Porter: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Bo Li: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Alex K Shalek: Broad Institute of MIT and Harvard, Cambridge, MA, USA. shalek@mit.edu. ORCID
Alexandra-Chlo�� Villani: Broad Institute of MIT and Harvard, Cambridge, MA, USA. avillani@mgh.harvard.edu. ORCID
Orit Rozenblatt-Rosen: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. orit.r.rosen@gmail.com. ORCID
Aviv Regev: Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. aviv.regev.sc@gmail.com. ORCID
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.
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