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
Author Information
Niyati Desai: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Azfar Neyaz: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Annamaria Szabolcs: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA. ORCID
Angela R Shih: Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Jonathan H Chen: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Vishal Thapar: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Linda T Nieman: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Alexander Solovyov: Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Arnav Mehta: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
David J Lieb: The Broad Institute, Cambridge, MA, 02142, USA.
Anupriya S Kulkarni: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Christopher Jaicks: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Katherine H Xu: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Michael J Raabe: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Christopher J Pinto: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Dejan Juric: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA. ORCID
Ivan Chebib: Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Robert B Colvin: Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA. ORCID
Arthur Y Kim: Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Robert Monroe: Advanced Cell Diagnostics, a Bio-Techne Brand, Newark, CA, 94560, USA.
Sarah E Warren: NanoString Inc., Seattle, WA, 98109, USA.
Patrick Danaher: NanoString Inc., Seattle, WA, 98109, USA. ORCID
Jason W Reeves: NanoString Inc., Seattle, WA, 98109, USA.
Jingjing Gong: NanoString Inc., Seattle, WA, 98109, USA.
Erroll H Rueckert: NanoString Inc., Seattle, WA, 98109, USA.
Benjamin D Greenbaum: Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Nir Hacohen: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA. ORCID
Stephen M Lagana: Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Miguel N Rivera: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
Lynette M Sholl: Department of Pathology, Brigham and Woman's Hospital, Boston, MA, 02115, USA. ORCID
James R Stone: Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA. jrstone@mgh.harvard.edu. ORCID
David T Ting: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA. dting1@mgh.harvard.edu. ORCID
Vikram Deshpande: Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA. vdeshpande@mgh.harvard.edu. ORCID
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.
