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

2021; Nature Portfolio; Volume: 595; Issue: 7865 Linguagem: Inglês

10.1038/s41586-021-03570-8

1476-4687

Toni 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 Pita-Juárez, Devan Phillips, Jana Biermann, Zohar Bloom‐Ackermann, Nikolaos Barkas, Andrea Ganna, James Gomez, Johannes C. Melms, Igor Katsyv, Erica Normandin, Pourya Naderi Yeganeh, Yury Popov, Siddharth S. Raju, Sebastian Niezen, Linus Tsai, Katherine J. Siddle, Malika Sud, Victoria M. Tran, Shamsudheen Karuthedath Vellarikkal, Yiping Wang, Liat Amir-Zilberstein, Deepak Atri, Joseph Beechem, Olga R. Brook, Jonathan H. Chen, Prajan Divakar, Phylicia Dorceus, J Engreitz, Adam L. Essene, Donna M. Fitzgerald, Robin Fropf, Steven Gazal, Joshua Gould, John Grzyb, Tyler Harvey, Jonathan L. Hecht, Tyler Hether, Judit Jané‐Valbuena, Michael Leney-Greene, Hui Ma, Cristin McCabe, Daniel E. McLoughlin, Eric Miller, Christoph Muus, Mari Niemi, Robert F. Padera, Liuliu Pan, Deepti Pant, Carmel Pe’er, Jenna Pfiffner-Borges, Christopher J. Pinto, Jacob Plaisted, Jason Reeves, Marty Ross, Melissa A. Rudy, Erroll H. Rueckert, Michelle Siciliano, Alexander Sturm, Ellen Todres, Avinash Waghray, Sarah Warren, Shuting Zhang, Daniel R. Zollinger, Lisa A. Cosimi, Rajat M. Gupta, Nir Hacohen, Hanina Hibshoosh, Yoshihide Hayashizaki, Alkes L. Price, Jayaraj Rajagopal, Purushothama Rao Tata, Stefan Riedel, Gyöngyi Szabó, Timothy L. Tickle, Patrick T. Ellinor, Deborah T. Hung, Pardis C. Sabeti, Richard Novák, 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 Porter, Bo Li, Alex K. Shalek, Alexandra–Chloé Villani, Orit Rozenblatt–Rosen, Aviv Regev,

SARS-CoV-2 and COVID-19 Research

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. Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.