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 () and Vikram Deshpande ()
Additional contact information
Niyati Desai: Massachusetts General Hospital Cancer Center
Azfar Neyaz: Massachusetts General Hospital Cancer Center
Annamaria Szabolcs: Massachusetts General Hospital Cancer Center
Angela R. Shih: Massachusetts General Hospital
Jonathan H. Chen: Massachusetts General Hospital Cancer Center
Vishal Thapar: Massachusetts General Hospital Cancer Center
Linda T. Nieman: Massachusetts General Hospital Cancer Center
Alexander Solovyov: Memorial Sloan Kettering Cancer Center
Arnav Mehta: Massachusetts General Hospital Cancer Center
David J. Lieb: The Broad Institute
Anupriya S. Kulkarni: Massachusetts General Hospital Cancer Center
Christopher Jaicks: Massachusetts General Hospital Cancer Center
Katherine H. Xu: Massachusetts General Hospital Cancer Center
Michael J. Raabe: Massachusetts General Hospital Cancer Center
Christopher J. Pinto: Massachusetts General Hospital Cancer Center
Dejan Juric: Massachusetts General Hospital Cancer Center
Ivan Chebib: Massachusetts General Hospital
Robert B. Colvin: Massachusetts General Hospital
Arthur Y. Kim: Massachusetts General Hospital
Robert Monroe: Advanced Cell Diagnostics, a Bio-Techne Brand
Sarah E. Warren: NanoString Inc.
Patrick Danaher: NanoString Inc.
Jason W. Reeves: NanoString Inc.
Jingjing Gong: NanoString Inc.
Erroll H. Rueckert: NanoString Inc.
Benjamin D. Greenbaum: Memorial Sloan Kettering Cancer Center
Nir Hacohen: Massachusetts General Hospital Cancer Center
Stephen M. Lagana: Columbia University Irving Medical Center
Miguel N. Rivera: Massachusetts General Hospital Cancer Center
Lynette M. Sholl: Brigham and Woman’s Hospital
James R. Stone: Massachusetts General Hospital
David T. Ting: Massachusetts General Hospital Cancer Center
Vikram Deshpande: Massachusetts General Hospital Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20139-7

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