Systems biological assessment of immunity to severe and mild COVID-19 infections
The recent emergence of COVID-19 presents a major global crisis. Profound knowledge gaps remain about the interaction between the virus and the immune system. Here, we used a systems biology approach to analyze immune responses in 76 COVID-19 patients and 69 age and sex- matched controls, from Hong Kong and Atlanta. Mass cytometry revealed prolonged plasmablast and effector T cell responses, reduced myeloid expression of HLA-DR and inhibition of mTOR signaling in plasmacytoid DCs (pDCs) during infection. Production of pro-inflammatory cytokines  plasma levels of inflammatory mediators, including EN-RAGE, TNFSF14, and Oncostatin-M, which correlated with disease severity, and increased bacterial DNA and endotoxin in plasma in  and reduced HLA-DR and CD86 but enhanced EN-RAGE expression in myeloid cells in severe  transient expression of IFN stimulated genes in moderate infections, consistent with transcriptomic analysis of bulk PBMCs, that correlated with transient and low levels of plasma  COVID-19. Overall design: RNAseq analysis of PBMCs in a group of 17 COVID-19 subjects and 17 healthy controls