Single-cell multi-omics analysis of the immune response in COVID-19

Abstract

Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

Systems vaccinology of the BNT162b2 mRNA vaccine in humans

“…because they expressed CD14, CD1c and CD274 known to be expressed by myeloid-derived suppressor cells (MDSCs) 4,[20][21][22] , we combined and analyzed innate immune cells (myeloid cells and pDCs) from this study with two previous studies 4,23 after batch correction using Harmony 24 . Well-annotated cell types such as monocytes and DCs overlapped between the datasets, but the C8 was non-overlapping (Extended Data Fig.…”

Dysregulation of Pulmonary Responses in Severe COVID-19

“…The dysregulation of pulmonary responses, including decreased TH17 cells (and CD8 + T cells [ 10 ]) and IFN-I (the latter is associated with impaired TLR7 and TLR8 expression), and the elevation of IgA, MMPs, MUC1, hyaluronic acid, and PAI-I (as well as myeloid cells [ 4 , 5 , 10 ]), is correlated with the disease severity (see more discussion in Figure 3 ). Amongst the above-mentioned factors, IFN-I and PAI-1 are dysregulated in older age, male gender, and preexisting diseases that are associated with increased risk to develop severe disease, and we propose the underexpression of IFN-I (and TLR7/TLR8) and the hypersecretion of PAI-1 as potential biomarkers to predict the susceptibility to severe COVID-19 (and maybe also other lung infections).…”

“…Poor outcomes are associated with older age (especially over 65) and underlying conditions including diabetes, cardiovascular disease, hypertension, obesity, and chronic obstructive pulmonary disease (COPD) [ 1 ]. Heightened serum levels of IL-6, C-reactive protein (CRP) and D-dimer, lymphopenia, neutrophilia, and other complications have been reported in severe COVID-19 [ 2 , 3 ], associated with the dysregulation of myeloid responses, especially in the lung [ 4 , 5 ]. In severe cases, cytokine release syndrome (also called “cytokine storm”) results in acute respiratory distress syndrome (ARDS) with drowning edema in the lung, which is broadly accepted as one of the major causes of death [ 6 ].…”

Exploiting Single-Cell Tools in Gene and Cell Therapy

“…The efficacy of multimodal single-cell screens, such as CITE-seq has been particularly evident throughout the scientific response to the COVID-19 outbreak. Combined efforts to screen >780,000 single PBMCs from COVID-19 patients and healthy donors using CITE-seq revealed the immune response to COVID-19 infections and its role in disease pathology (296). Such studies provide a prominent example how single-cell multiomics can provide rapid insight into previously unknown diseases and help inform the development of effective therapeutics.…”