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

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

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.