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; Aviv Regev

doi:10.1038/s41586-021-03570-8

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, Aviv Regev

Research output: Contribution to journal › Article › peer-review

622 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	107-113
Number of pages	7
Journal	Nature
Volume	595
Issue number	7865
DOIs	https://doi.org/10.1038/s41586-021-03570-8
State	Published - 1 Jul 2021
Externally published	Yes

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Delorey, T. M., Ziegler, C. G. K., Heimberg, G., Normand, R., Yang, Y., Segerstolpe, Å., Abbondanza, D., Fleming, S. J., Subramanian, A., Montoro, D. T., Jagadeesh, K. A., Dey, K. K., Sen, P., Slyper, M., Pita-Juárez, Y. H., Phillips, D., Biermann, J., Bloom-Ackermann, Z., Barkas, N., ... 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

@article{94d975587ea04f24a60d1d79ad3cf7bd,

title = "COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets",

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.",

author = "Delorey, \{Toni M.\} and Ziegler, \{Carly G.K.\} and Graham Heimberg and Rachelly Normand and Yiming Yang and {\AA}sa Segerstolpe and Domenic Abbondanza and Fleming, \{Stephen J.\} and Ayshwarya Subramanian and Montoro, \{Daniel T.\} and Jagadeesh, \{Karthik A.\} and Dey, \{Kushal K.\} and Pritha Sen and Michal Slyper and Pita-Ju{\'a}rez, \{Yered H.\} and Devan Phillips and Jana Biermann and Zohar Bloom-Ackermann and Nikolaos Barkas and Andrea Ganna and James Gomez and Melms, \{Johannes C.\} and Igor Katsyv and Erica Normandin and Pourya Naderi and Popov, \{Yury V.\} and Raju, \{Siddharth S.\} and Sebastian Niezen and Tsai, \{Linus T.Y.\} and Siddle, \{Katherine J.\} and Malika Sud and Tran, \{Victoria M.\} and Vellarikkal, \{Shamsudheen K.\} and Yiping Wang and Liat Amir-Zilberstein and Atri, \{Deepak S.\} and Joseph Beechem and Brook, \{Olga R.\} and Jonathan Chen and Prajan Divakar and Phylicia Dorceus and Engreitz, \{Jesse M.\} and Adam Essene and Fitzgerald, \{Donna M.\} and Robin Fropf and Steven Gazal and Joshua Gould and John Grzyb and Tyler Harvey and Jonathan Hecht and Tyler Hether and Judit Jan{\'e}-Valbuena and Michael Leney-Greene and Hui Ma and Cristin McCabe and McLoughlin, \{Daniel E.\} and Miller, \{Eric M.\} and Christoph Muus and Mari Niemi and Robert Padera and Liuliu Pan and Deepti Pant and Carmel Pe{\textquoteright}er and Jenna Pfiffner-Borges and Pinto, \{Christopher J.\} and Jacob Plaisted and Jason Reeves and Marty Ross and Melissa Rudy and Rueckert, \{Erroll H.\} and Michelle Siciliano and Alexander Sturm and Ellen Todres and Avinash Waghray and Sarah Warren and Shuting Zhang and Zollinger, \{Daniel R.\} and Lisa Cosimi and Gupta, \{Rajat M.\} and Nir Hacohen and Hanina Hibshoosh and Winston Hide and Price, \{Alkes L.\} and Jayaraj Rajagopal and Tata, \{Purushothama Rao\} and Stefan Riedel and Gyongyi Szabo and Tickle, \{Timothy L.\} and Ellinor, \{Patrick T.\} and Deborah Hung and Sabeti, \{Pardis C.\} and Richard Novak and Robert Rogers and Ingber, \{Donald E.\} and Jiang, \{Z. Gordon\} and Dejan Juric and Mehrtash Babadi and Farhi, \{Samouil L.\} and Benjamin Izar and Stone, \{James R.\} and Vlachos, \{Ioannis S.\} and Solomon, \{Isaac H.\} and Orr Ashenberg and Porter, \{Caroline B.M.\} and Bo Li and Shalek, \{Alex K.\} and Villani, \{Alexandra Chlo{\'e}\} and Orit Rozenblatt-Rosen and Aviv Regev",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = jul,

day = "1",

doi = "10.1038/s41586-021-03570-8",

language = "English",

volume = "595",

pages = "107--113",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7865",

}

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, LTY, 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, AC, Rozenblatt-Rosen, O & Regev, A 2021, 'COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets', Nature, vol. 595, no. 7865, pp. 107-113. https://doi.org/10.1038/s41586-021-03570-8

TY - JOUR

T1 - COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

AU - Delorey, Toni M.

AU - Ziegler, Carly G.K.

AU - Heimberg, Graham

AU - Normand, Rachelly

AU - Yang, Yiming

AU - Segerstolpe, Åsa

AU - Abbondanza, Domenic

AU - Fleming, Stephen J.

AU - Subramanian, Ayshwarya

AU - Montoro, Daniel T.

AU - Jagadeesh, Karthik A.

AU - Dey, Kushal K.

AU - Sen, Pritha

AU - Slyper, Michal

AU - Pita-Juárez, Yered H.

AU - Phillips, Devan

AU - Biermann, Jana

AU - Bloom-Ackermann, Zohar

AU - Barkas, Nikolaos

AU - Ganna, Andrea

AU - Gomez, James

AU - Melms, Johannes C.

AU - Katsyv, Igor

AU - Normandin, Erica

AU - Naderi, Pourya

AU - Popov, Yury V.

AU - Raju, Siddharth S.

AU - Niezen, Sebastian

AU - Tsai, Linus T.Y.

AU - Siddle, Katherine J.

AU - Sud, Malika

AU - Tran, Victoria M.

AU - Vellarikkal, Shamsudheen K.

AU - Wang, Yiping

AU - Amir-Zilberstein, Liat

AU - Atri, Deepak S.

AU - Beechem, Joseph

AU - Brook, Olga R.

AU - Chen, Jonathan

AU - Divakar, Prajan

AU - Dorceus, Phylicia

AU - Engreitz, Jesse M.

AU - Essene, Adam

AU - Fitzgerald, Donna M.

AU - Fropf, Robin

AU - Gazal, Steven

AU - Gould, Joshua

AU - Grzyb, John

AU - Harvey, Tyler

AU - Hecht, Jonathan

AU - Hether, Tyler

AU - Jané-Valbuena, Judit

AU - Leney-Greene, Michael

AU - Ma, Hui

AU - McCabe, Cristin

AU - McLoughlin, Daniel E.

AU - Miller, Eric M.

AU - Muus, Christoph

AU - Niemi, Mari

AU - Padera, Robert

AU - Pan, Liuliu

AU - Pant, Deepti

AU - Pe’er, Carmel

AU - Pfiffner-Borges, Jenna

AU - Pinto, Christopher J.

AU - Plaisted, Jacob

AU - Reeves, Jason

AU - Ross, Marty

AU - Rudy, Melissa

AU - Rueckert, Erroll H.

AU - Siciliano, Michelle

AU - Sturm, Alexander

AU - Todres, Ellen

AU - Waghray, Avinash

AU - Warren, Sarah

AU - Zhang, Shuting

AU - Zollinger, Daniel R.

AU - Cosimi, Lisa

AU - Gupta, Rajat M.

AU - Hacohen, Nir

AU - Hibshoosh, Hanina

AU - Hide, Winston

AU - Price, Alkes L.

AU - Rajagopal, Jayaraj

AU - Tata, Purushothama Rao

AU - Riedel, Stefan

AU - Szabo, Gyongyi

AU - Tickle, Timothy L.

AU - Ellinor, Patrick T.

AU - Hung, Deborah

AU - Sabeti, Pardis C.

AU - Novak, Richard

AU - Rogers, Robert

AU - Ingber, Donald E.

AU - Jiang, Z. Gordon

AU - Juric, Dejan

AU - Babadi, Mehrtash

AU - Farhi, Samouil L.

AU - Izar, Benjamin

AU - Stone, James R.

AU - Vlachos, Ioannis S.

AU - Solomon, Isaac H.

AU - Ashenberg, Orr

AU - Porter, Caroline B.M.

AU - Li, Bo

AU - Shalek, Alex K.

AU - Villani, Alexandra Chloé

AU - Rozenblatt-Rosen, Orit

AU - Regev, Aviv

PY - 2021/7/1

Y1 - 2021/7/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85105172511

U2 - 10.1038/s41586-021-03570-8

DO - 10.1038/s41586-021-03570-8

M3 - Article

C2 - 33915569

AN - SCOPUS:85105172511

SN - 0028-0836

VL - 595

SP - 107

EP - 113

JO - Nature

JF - Nature

IS - 7865

ER -

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

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