Figure 2.

Replication of EN-RAGE severity association across sample types in both COVID-19 and non-COVID-19 acute lung injury (COMET cohort)

(A) UMAP plots with cell type annotations. Each point represents a single cell, colored by cell type. Each panel shows a different sample type, as indicated. PBMC: peripheral blood mononuclear cells, WB, whole blood; ETA, endotracheal aspirates.

(B) UMAP plots showing EN-RAGE signature score. Each point represented a single cell colored by the expression signature value.

(C) Pseudo-bulk expression profiles within myeloid cells. Each point represents the pseudo-bulk gene expression signature score for a cell type in a patient sample. PBMC severity: Moderate = no supplemental O₂, severe = supplemental O₂ and critical = mechanical ventilation. Whole blood severity: Mild/Moderate = 0 days on ventilator and no more than 1 day in ICU, Severe patients had ≥1 day on ventilator. ETA: Critical = VFDS = 0 (ventilation for ≥28 days or death), severe ETA = VFDS>0. Significance was tested using a t test across the indicated groups (n.s. = p > 0.05, ∗∗ = p < 0.01; ∗∗∗ = p < 0.001). Sample numbers per cohort: PBMC healthy, n = 11; PBMC COVID− moderate, n = 4; PBMC COVID− severe, n = 6; PBMC COVID− critical, n = 3; PBMC COVID+ moderate, n = 12; PBMC COVID+ severe, n = 10; PBMC COVID+ critical, n = 14. WB healthy, n = 14; WB COVID− mild, n = 4; WB COVID− severe, n = 1; WB COVID+ mild, n = 8; WB COVID+ severe, n = 5. ETA COVID− moderate/severe, n = 2; ETA COVID− critical, n = 1; ETA COVID+ moderate/severe, n = 5; ETA COVID+ critical, n = 8. Boxes represent the upper and lower quartile of the sample distribution, with the center line showing the median. Whiskers show the most extreme point up to 1.5x the inter-quartile range of the sample distribution.

(D) Frequencies of myeloid populations in either PBMC or BAL. Each point represents a patient sample, colored as in panel (C).