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.
Highlights
The COVID-19 global pandemic has caused >120 million infections and 2.6 million deaths[1,2]
Individuals with non-COVID-19 severe respiratory illness and healthy volunteers administered with intravenous lipopolysaccharide (IV-LPS) as a surrogate for an acute systemic inflammatory response (Fig. 1a and Supplementary Table 2)
Peripheral blood monocytes and dendritic cells (DCs) exhibit an interferon response to infection
Summary
The COVID-19 global pandemic has caused >120 million infections and 2.6 million deaths (as of 17 March 2021)[1,2]. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded RNA betacoronavirus that enters host cells through receptors such as angiotensin-converting enzyme 2 (ACE2) and neuropilin (NRP1), which are expressed widely, including in nasal epithelium[4–6]. T cells with disease severity and reduced interferon (IFN)-γ production by lymphocytes have been reported[9]. Classical monocytes have been shown to display a type 1 IFN inflammatory signature[6]; low levels of IFNα coupled with a reduction in plasmacytoid dendritic cells (DCs) have been reported in patients with critical disease[12]. To better understand the coordinated systemic immune response in individuals with asymptomatic and symptomatic COVID-19, we performed combined single-cell transcriptome, cell-surface protein and lymphocyte antigen receptor repertoire analysis of peripheral blood of a cross-sectional patient cohort and integrated results across three UK medical centers
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