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

Publication ,  Journal Article
Delorey, TM; Ziegler, CGK; Heimberg, G; Normand, R; Yang, Y; Segerstolpe, Å; Abbondanza, D; Fleming, SJ; Subramanian, A; Montoro, DT; Dey, KK ...
Published in: Nature
July 2021

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 2021

Volume

595

Issue

7865

Start / End Page

107 / 113

Location

England

Related Subject Headings

  • Viral Load
  • Single-Cell Analysis
  • SARS-CoV-2
  • Regeneration
  • RNA, Viral
  • Pulmonary Alveoli
  • Phagocytes
  • Organ Specificity
  • Myocardium
  • Middle Aged
 

Citation

APA
Chicago
ICMJE
MLA
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Delorey, T. M., Ziegler, C. G. K., Heimberg, G., Normand, R., Yang, Y., Segerstolpe, Å., … Regev, A. (2021). COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature, 595(7865), 107–113. https://doi.org/10.1038/s41586-021-03570-8
Delorey, Toni M., Carly G. K. Ziegler, Graham Heimberg, Rachelly Normand, Yiming Yang, Åsa Segerstolpe, Domenic Abbondanza, et al. “COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.Nature 595, no. 7865 (July 2021): 107–13. https://doi.org/10.1038/s41586-021-03570-8.
Delorey TM, Ziegler CGK, Heimberg G, Normand R, Yang Y, Segerstolpe Å, et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature. 2021 Jul;595(7865):107–13.
Delorey, Toni M., et al. “COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.Nature, vol. 595, no. 7865, July 2021, pp. 107–13. Pubmed, doi:10.1038/s41586-021-03570-8.
Delorey TM, Ziegler CGK, Heimberg G, Normand R, Yang Y, Segerstolpe Å, Abbondanza D, Fleming SJ, Subramanian A, Montoro DT, Jagadeesh KA, Dey KK, Sen P, Slyper M, Pita-Juárez YH, Phillips D, Biermann J, Bloom-Ackermann Z, Barkas N, Ganna A, Gomez J, Melms JC, Katsyv I, Normandin E, Naderi P, Popov YV, Raju SS, Niezen S, Tsai LT-Y, Siddle KJ, Sud M, Tran VM, Vellarikkal SK, Wang Y, Amir-Zilberstein L, Atri DS, Beechem J, Brook OR, Chen J, Divakar P, Dorceus P, Engreitz JM, Essene A, Fitzgerald DM, Fropf R, Gazal S, Gould J, Grzyb J, Harvey T, Hecht J, Hether T, Jané-Valbuena J, Leney-Greene M, Ma H, McCabe C, McLoughlin DE, Miller EM, Muus C, Niemi M, Padera R, Pan L, Pant D, Pe’er C, Pfiffner-Borges J, Pinto CJ, Plaisted J, Reeves J, Ross M, Rudy M, Rueckert EH, Siciliano M, Sturm A, Todres E, Waghray A, Warren S, Zhang S, Zollinger DR, Cosimi L, Gupta RM, Hacohen N, Hibshoosh H, Hide W, Price AL, Rajagopal J, Tata PR, Riedel S, Szabo G, Tickle TL, Ellinor PT, Hung D, Sabeti PC, Novak R, Rogers R, Ingber DE, Jiang ZG, Juric D, Babadi M, Farhi SL, Izar B, Stone JR, Vlachos IS, Solomon IH, Ashenberg O, Porter CBM, Li B, Shalek AK, Villani A-C, Rozenblatt-Rosen O, Regev A. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature. 2021 Jul;595(7865):107–113.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 2021

Volume

595

Issue

7865

Start / End Page

107 / 113

Location

England

Related Subject Headings

  • Viral Load
  • Single-Cell Analysis
  • SARS-CoV-2
  • Regeneration
  • RNA, Viral
  • Pulmonary Alveoli
  • Phagocytes
  • Organ Specificity
  • Myocardium
  • Middle Aged