In this preprint, Desai et al. provide a spatial analysis of SARS-CoV-2 infection from autopsies of 24 deceased patients with COVID-19. Intra-pulmonary samples were stratified according to viral load using RNA in situ hybridization. They identified a spectrum of viral load between patients and within the same patient. Patients with high viral load had shorter duration of disease, which correlated with distinct transcriptional profiles, including type I/II interferon pathway genes and genes associated with wound healing. Quantification of immune cell subtypes indicated that M1-type macrophages were more abundant in areas positive for SARS-CoV-2 but showed spatially contrasted immune infiltrations within the same patient. Together, these results highlight the intra-pulmonary heterogeneity of immune responses in infected lungs.