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; 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 lung infection and severity of pulmonary disease is not fully understood. We analyzed 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- and intra- patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the virus corresponded to distinct spatial expression of interferon response genes and immune checkpoint genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.