Transcriptomic profiling of peripheral immune cells reveals distinct innate immune signatures associated with disease severity in COVID-19 viremia patients

SARS-CoV-2 is an emerging mosquito-borne pathogen with increasing public health significance. To characterize interconnected immune responses to SARS-CoV-2, we here examined transcriptional signatures of CD4 and CD8 T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three individuals with naturally-acquired SARS-CoV-2 infection. Whole transcriptome analysis demonstrated that all seven immune cells among PBMCs were clustered together with disease severity regardless of cell types. mDCs and pDCs gene signatures distinct disease severity. A distinct phenotype was observed in severe patients with or without plasma viremia, demonstrating a highly impaired induction of Interferon stimulated genes (ISGs) accompanied by imbalanced type I interferon sensing and an excessive inflammatory response. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in blood from different disease severe COVID-19 patients. Overall design: The current study comprehensively examined 7 immune cell types including CD8 T cells, CD4 T cells, B cells, and NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) from three different groups, including moderate patients without detectable plasma viral load (nM=5), severe patients without detectable plasma viral load (nS=5), severe patients with detectable plasma viral load (vS=5), and healthy control (HD=5, 2 are included in this dataset, another 3 were previously submitted to GEO dataset GSE132228)