Fig 1: High levels of SPP1 and S100A12 are associated with a severe COVID-19 disease trajectory.(A) Patients and healthy donors, shown as the following: n = 121 patients with acute pneumonia (n = 29 community acquired SARS-CoV-2– pneumonia, n = 29 mild/moderate COVID-19, n = 63 severe COVID-19), convalescent COVID-19 (n = 41), and healthy controls (n = 10). Representative images of lung CT scans. (B) Plasma levels of SPP1, S100A12, GAS6, and PROS1 in groups as in A. (C) Spearman’s rank correlations between SPP1, S100A12, GAS6, and PROS1 plasma levels in patients with acute COVID-19 pneumonia (n = 92) with demographic and clinical parameters. Each box displays the r value, and an asterisk indicates statistical significance of P < 0.05. (D) Plasma levels of SPP1, S100A12, GAS6, and PROS1 in patients with acute COVID-19 pneumonia (n = 92) stratified based on lung functions measured by PaO2/FiO2 at the time of hospital admission. Severe respiratory failure was defined by PaO2/FiO2 = 200. (E) Percentage of acute COVID-19 pneumonia patients (n = 92) with PaO2/FiO2 = 200 based on high plasma levels of SPP1 (=108 ng/mL), S100A12 (=59 ng/mL), GAS6 (=24 ng/mL), and PROS1 (=15 µg/mL). (F) COVID-19 patient plasma levels of SPP1, S100A12, GAS6, and PROS1 at the time of hospital admission (n = 92) stratified based on a patient’s subsequent need to be transferred to ICU. (G) Percentage of patients with acute COVID-19 pneumonia (n = 92) transferred to ICU during the hospitalization based on having high levels of SPP1 (=108 ng/mL), S100A12 (=59 ng/mL), GAS6 (=24 ng/mL), and PROS1 (=15 µg/mL) at the time of hospital admission. (B, D, and F) Data are presented as violin plots with median and interquartile range. Asterisk indicates 1-way ANOVA (Kruskal-Wallis test) with Dunn’s correction for multiple comparisons if more than 2 groups were compared (B), or 2-sided Mann-Whitney U was used when 2 groups were compared (B and D–G). (H) Kaplan-Meier analysis of the rate of transfer of COVID-19 patients to ICU based on their cut-off values for SPP1, S100A12, GAS6, and PROS1 at the time of hospital admission.
Fig 2: Increased SPP1 and S100A12 levels persist in post–COVID-19 phase.(A) Representative images of lung CT scans (transversal and sagittal view) of a COVID-19 patient taken during acute pneumonia and during convalescence (68.60 ± 4.36 days after hospital discharge). (B) Plasma levels of SPP1, S100A12, GAS6, and PROS1 in paired plasma samples from COVID-19 patients at the time of acute pneumonia and at the convalescent phase (n = 26). (C) Plasma levels of SPP1, S100A12, GAS6, and PROS1 in convalescent COVID-19 patients (n = 41) stratified based on the severity of prior acute pneumonia and compared with the levels of healthy donors (n = 10). (D) Plasma levels of IL-6 in acute pneumonias and post–COVID-19. (E) SPP1, S100A12, GAS6, and PROS1 in convalescent COVID-19 patients (n = 41) stratified based on suffering (n = 36) or not (n = 5) at least 1 of the symptoms (fatigue, musculoskeletal, or respiratory symptoms). (B) Data are presented as before-and-after plot. Wilcoxon test on paired samples was used, and exact P values are provided on the graphs. (C–E) Data are presented as violin plots with median and interquartile range. Asterisks indicate 1-way ANOVA with correction for multiple comparisons if more than 2 groups were compared, or 2-sided Mann-Whitney U test was used when 2 groups were compared (C–E). Exact P values are provided on the graphs.
Fig 3: COVID-19 BALF FABP4+ and RA synovial TREM2+ macrophages share transcriptomic profiles and regulatory TAM receptor pathways.(A) Venn diagram illustrating numbers of unique and shared marker genes of ST TREM2hi and BALF FABP4+ macrophage clusters as described in Figure 1. Marker genes were identified prior to integration of data sets (19, 24) and were calculated using MAST, setting a minimum percentage of cells in clusters expressing each marker to 40%. Genes considered differentially expressed at P < 0.05 after Bonferroni correction. (B) Heatmap illustrating scaled, pseudobulk expression of shared upregulated marker genes from ST and BALF clusters indicated in A. (C) Split UMAP plots comparing BALF macrophage clusters in health, and in mild and severe COVID-19, illustrating changes in expression of the TAM receptors AXL and MerTK, with their respective preferred ligands GAS6 and PROS1. Intensity of purple indicates expression level. (D) Heatmap illustrating scaled, pseudobulk expression of TAM receptors and associated ligands by each BALF cluster, across patient groups. TAM receptors and their ligands were significantly differentially expressed in severe COVID-19 versus healthy tissues (P = 0.005), with Bonferroni correction for multiple comparison, as confirmed by MAST.
Supplier Page from Novus Biologicals, a Bio-Techne Brand for Human Protein S/PROS1 ELISA Kit (Colorimetric)