Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection

Niyati Desai; Azfar Neyaz; Annamaria Szabolcs; Angela R. Shih; Jonathan H. Chen; Vishal Thapar; Linda T. Nieman; Alexander Solovyov; Arnav Mehta; David J. Lieb; Anupriya S. Kulkarni; Christopher Jaicks; Katherine H. Xu; Michael J. Raabe; Christopher J. Pinto; Dejan Juric; Ivan Chebib; Robert B. Colvin; Arthur Y. Kim; Robert Monroe; Sarah E. Warren; Patrick Danaher; Jason W. Reeves; Jingjing Gong; Erroll H. Rueckert; Benjamin D. Greenbaum; Nir Hacohen; Stephen M. Lagana; Miguel N. Rivera; Lynette M. Sholl; James R. Stone; David T. Ting; Vikram Deshpande

doi:10.1038/s41467-020-20139-7

Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection

Niyati Desai, Azfar Neyaz, Annamaria Szabolcs, Angela R. Shih, Jonathan H. Chen, Vishal Thapar, Linda T. Nieman, Alexander Solovyov, Arnav Mehta, David J. Lieb, Anupriya S. Kulkarni, Christopher Jaicks, Katherine H. Xu, Michael J. Raabe, Christopher J. Pinto, Dejan Juric, Ivan Chebib, Robert B. Colvin, Arthur Y. Kim, Robert MonroeSarah E. Warren, Patrick Danaher, Jason W. Reeves, Jingjing Gong, Erroll H. Rueckert, Benjamin D. Greenbaum, Nir Hacohen, Stephen M. Lagana, Miguel N. Rivera, Lynette M. Sholl, James R. Stone, David T. Ting, Vikram Deshpande

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Abstract

The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.

Original language	English
Article number	6319
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20139-7
State	Published - Dec 2020
Externally published	Yes

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Desai, N., Neyaz, A., Szabolcs, A., Shih, A. R., Chen, J. H., Thapar, V., Nieman, L. T., Solovyov, A., Mehta, A., Lieb, D. J., Kulkarni, A. S., Jaicks, C., Xu, K. H., Raabe, M. J., Pinto, C. J., Juric, D., Chebib, I., Colvin, R. B., Kim, A. Y., ... Deshpande, V. (2020). Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection. Nature Communications, 11(1), Article 6319. https://doi.org/10.1038/s41467-020-20139-7

@article{639c485e214848569712c3fdbc8d8880,

title = "Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection",

abstract = "The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.",

author = "Niyati Desai and Azfar Neyaz and Annamaria Szabolcs and Shih, {Angela R.} and Chen, {Jonathan H.} and Vishal Thapar and Nieman, {Linda T.} and Alexander Solovyov and Arnav Mehta and Lieb, {David J.} and Kulkarni, {Anupriya S.} and Christopher Jaicks and Xu, {Katherine H.} and Raabe, {Michael J.} and Pinto, {Christopher J.} and Dejan Juric and Ivan Chebib and Colvin, {Robert B.} and Kim, {Arthur Y.} and Robert Monroe and Warren, {Sarah E.} and Patrick Danaher and Reeves, {Jason W.} and Jingjing Gong and Rueckert, {Erroll H.} and Greenbaum, {Benjamin D.} and Nir Hacohen and Lagana, {Stephen M.} and Rivera, {Miguel N.} and Sholl, {Lynette M.} and Stone, {James R.} and Ting, {David T.} and Vikram Deshpande",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

doi = "10.1038/s41467-020-20139-7",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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Desai, N, Neyaz, A, Szabolcs, A, Shih, AR, Chen, JH, Thapar, V, Nieman, LT, Solovyov, A, Mehta, A, Lieb, DJ, Kulkarni, AS, Jaicks, C, Xu, KH, Raabe, MJ, Pinto, CJ, Juric, D, Chebib, I, Colvin, RB, Kim, AY, Monroe, R, Warren, SE, Danaher, P, Reeves, JW, Gong, J, Rueckert, EH, Greenbaum, BD, Hacohen, N, Lagana, SM, Rivera, MN, Sholl, LM, Stone, JR, Ting, DT & Deshpande, V 2020, 'Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection', Nature Communications, vol. 11, no. 1, 6319. https://doi.org/10.1038/s41467-020-20139-7

TY - JOUR

T1 - Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection

AU - Desai, Niyati

AU - Neyaz, Azfar

AU - Szabolcs, Annamaria

AU - Shih, Angela R.

AU - Chen, Jonathan H.

AU - Thapar, Vishal

AU - Nieman, Linda T.

AU - Solovyov, Alexander

AU - Mehta, Arnav

AU - Lieb, David J.

AU - Kulkarni, Anupriya S.

AU - Jaicks, Christopher

AU - Xu, Katherine H.

AU - Raabe, Michael J.

AU - Pinto, Christopher J.

AU - Juric, Dejan

AU - Chebib, Ivan

AU - Colvin, Robert B.

AU - Kim, Arthur Y.

AU - Monroe, Robert

AU - Warren, Sarah E.

AU - Danaher, Patrick

AU - Reeves, Jason W.

AU - Gong, Jingjing

AU - Rueckert, Erroll H.

AU - Greenbaum, Benjamin D.

AU - Hacohen, Nir

AU - Lagana, Stephen M.

AU - Rivera, Miguel N.

AU - Sholl, Lynette M.

AU - Stone, James R.

AU - Ting, David T.

AU - Deshpande, Vikram

PY - 2020/12

Y1 - 2020/12

N2 - The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.

AB - The relationship of SARS-CoV-2 pulmonary infection and severity of disease is not fully understood. Here we show analysis of autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter-patient and intra-patient heterogeneity of pulmonary virus infection. There is a spectrum of high and low virus cases associated with duration of disease. High viral cases have high activation of interferon pathway genes and a predominant M1-like macrophage infiltrate. Low viral cases are more heterogeneous likely reflecting inherent patient differences in the evolution of host response, but there is consistent indication of pulmonary epithelial cell recovery based on napsin A immunohistochemistry and RNA expression of surfactant and mucin genes. Using a digital spatial profiling platform, we find the virus corresponds to distinct spatial expression of interferon response genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.

UR - http://www.scopus.com/inward/record.url?scp=85097405428&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-20139-7

DO - 10.1038/s41467-020-20139-7

M3 - Article

C2 - 33298930

AN - SCOPUS:85097405428

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 6319

ER -

Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection

Abstract

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