Figure 2: Shifts in circulating leukocyte composition in critical COVID-19.
a) Experimental set-up. Frozen PBMCs are thawed, multiplexed, stained and processed using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq). b) Marker genes for each of the 11 cell types identified including CD4+ T cells (T4), CD8+ T cells (T8), gamma delta T cells (Tgd), natural killer cells (NK), B cells (B), plasmablasts (PB), classical monocytes (cM), non-classical monocytes (ncM), conventional dendritic cells (cDC), plasmacytoid dendritic cells (pDC), and CD34+ hematopoietic progeneitors (Progen). c) UMAP projections of PBMCs from donors separated by COVID-19 status and severity. Cells are colored by type. d) Boxplots (showing median, 25th and 75th percentile) of the percentages of T8, PB, cMs and ncMs (y-axis) by COVID-19 status and severity level on day of hospital admission (D0). Each dot represents the percentage of a specific cell type per donor. Shown statistical comparisons are between cells from all C19+ critical donors (including the anti-IFN-α2 autoantibody donors) and healthy controls, C19− donors or combined C19+ Moderate-Severe donors. Other cell types can be found in Fig. S1. e) Boxplots of the percentages of T8, PB, cMs, ncMs (y-axis) in COVID-19 patients over day 0, 4, 7 and 14 since hospitalization (D0, D4, D7, D14). Other cell types can be found in Fig. S1. f) Scatterplot of SARS-CoV2 viral titer as measured by qRT-PCR in tracheal aspirates (inverse dCT, x-axis) and percentage of plasmablasts (PB) (y-axis) as quantified in donor-matched single-cell PBMC data (R = Pearson correlation). Holm’s multiple-testing corrected, permutation-based p-values: *** p < 0.001, ** p < 0.01, * p < 0.05, ns = not significant.