Figure 1.
Increased FV gene expression in circulating leukocytes in hospitalized patients with COVID-19
(A) Peripheral blood cells from healthy controls, healthcare workers and patients with COVID-19 express FV. Individuals represented by dots are grouped into 12 days time periods after onset of symptoms or a positive swab in asymptomatic healthcare workers (HCW). HC, healthy controls; A, HCW screening asymptomatic; B, HCW screening symptomatic; C, hospitalized mild disease; D, hospitalized requiring oxygen; E, hospitalized, intensive care. 0 to 12 days C versus HC p = 0.003; D versus HC p = 0. 0000008; E versus HC p < 0.00001. 13 to 24 days C versus HC p = 0.0054; D versus HC p = 0.045; E versus HC p < 0.00001. 25–36 days E versus HC p = 0.00003. 49 to 60 days E versus HC p < 0.0000. 61 to 72 days E versus HC p = 0.0006. Box plot indicates interquartial range.
(B) Weighted gene co-expression network analysis identified a module containing group of genes co-expressed with FV, in which FV is a hub gene and its expression correlates strongly with genes expressed in neutrophils (Figure S1). Mixed-effects model with quadratic time trend showing the longitudinal expression of the FV module over time, grouped by severity. Gray band indicates the IQR of HCs. A significant effect of time versus severity group interaction term (p = 3.33e-07) indicates that disease severity has a significant effect on longitudinal expression.
(C) scRNAseq of PBMCs derived from HC, HCW and patients with COVID-19 showed the highest expression of FV in CD4+, FoxP3+ Tregs, with expression also detected in monocytes and at lower levels in other CD4 cell subsets. FV expression was increased in Tregs versus CD4+ Naive cells in healthy controls (p = 8.33 × 10−4), and in severe COVID-19 versus healthy controls in CD14 monocytes (p = 0.016) but not other cell subsets. See also Figures S1, S3 and Table S1. Boxes denote IQR with median shown as horizontal bars. Whiskers extend to 1.5x the IQR; outliers are shown as individual points.