Multi-omic analysis resolves coordinated immune responses to mild, moderate and severe COVID-19. Su et al.

Host immune responses in controlling SARS-CoV-2 infection remain incompletely characterized across the spectrum of disease severities. Here, we present a comprehensive immune map spanning 464 proteins and 1050 metabolites in plasma integrated with single-cell transcriptomic and proteomic assays of 0.55 million PBMCs from 139 COVID-19 patients (265 samples). Our study reveals how the global plasma composition and the immune-cell phenotypic behaviors co-evolve with increasing severity, including a major shift between mild and moderate disease. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to COVID-19 and resolve the emergence of multiple novel phenotypes at the state of moderate disease. The coordinated immune- response axis independently aligns with plasma changes pointing to the loss of certain classes of metabolites under elevated inflammatory signaling. Our study provides a resource for unraveling the complex immune response to COVID-19 and may inform therapeutic development.