Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19

Abstract

Respiratory immune characteristics associated withCoronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8 + T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.

Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution

“…Treg cells), and pDCs in mild patients compared to both severe and control patients. Although severityspecific compositional changes in BALF samples remain largely unaddressed in the literature [27], the severity-specific lymphopenia of NK cells and CD4+ naive T cells that we report in BALF agrees with findings from compositional studies of PBMCs [30,31,34]. We additionally report severity-specific compositional shifts in lung mononuclear phagocyte populations and identify clusters expressing MRC1, C1QA, and FABP4 suggesting an M2 macrophage-like phenotype expanded in control subjects.…”

“…A total of 33 clusters were identified showing distinct separation in a two-dimensional UMAP space. Annotation of these clusters based on the expression of canonical cell type markers showed the presence of myeloid cells, lymphoid cells, and epithelial cells, closely matching the cell types found by the original publication [27]. Of 13 annotated cell types, 12 contained cells from mild, severe, and control donors, with the exception of plasma cells which were not recovered from mild donors (Figure S1A).…”

“…While many studies have endeavored to apply transcriptional profiling to understand the cellular dynamics underlying coronavirus infection, to our knowledge, a single integrative study directly comparing severity-specific responses in both the lung and blood compartments has not yet been reported. Previous analyses of BALF samples have shown neutrophil and proliferating T cell enrichment in severe over mild patients accompanied by CD8+ T cell lymphopenia, a shift towards inflammatory macrophage polarization, and increased transcriptional expression of a variety of cytokines [27,28]. Previous investigations of peripheral blood responses have shown various compositional shifts between severe and mild disease including cytopenias of monocytes, natural killer (NK) cells, dendritic cells (DCs), and T cells, [28,29,30,31,32] accompanied by increases in plasmablasts, B cells, and neutrophils [33,34,35,36].…”

“…An overarching unaddressed question is the possibility for therapeutic interventions to affect the lung and blood compartments differently; thus, generating comparative transcriptional data will be useful for determining efficacious treatment strategies for severe In this study, we present direct comparisons between severity-specific immunological signatures of COVID-19 in both the lung and blood compartments using identical methods. We re-analyzed two publicly available scRNA-seq datasets: one containing BALF cells of mild and severe patients as well as healthy control subjects from Liao et al [27] and one containing PBMCs of mild and severe patients as well as healthy control subjects from Wilk et al [32] For both of these datasets we conducted identical preprocessing, integration and analysis in order to obtain comparable results. We first evaluated differential gene expression and pathway-level changes between severe and mild patients for each cell type in the BALF and the PBMC datasets.…”

Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

“…Most patients seroconvert within 7-14 days of onset of infection and increases in plasmablasts have been reported (15,(20)(21)(22). However, the role of humoral responses in the control of SARS-CoV2 and pathogenesis of COVID-19 disease remains unclear.…”