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. 2021 Sep 5;10(9):e1339. doi: 10.1002/cti2.1339

Figure 7.

Figure 7

High‐dimensional analysis of all variables studied reveals coordinated immune responses and their association with disease severity (a) Spearman’s correlation mapping of indicated parameters for healthy controls (HCs), COVT1 and COVT2. Spearman’s rank correlation coefficient (ρ) was indicated by heat scale; Spearman’s P‐value significance levels were corrected using the Benjamini–Hochberg method significance (*P < 0.05, **P < 0.01 and ***P < 0.001). PBs, plasmablasts. R3, CXCR3. R4, CXCR4. ME, memory. cTfh, circulating T follicular helper cells. CM, central memory. EM3, effector memory type 3. pDCs, plasmacytoid dendritic cells. mDCs, myeloid dendritic cells. Baso, basophils. NK, natural killer cells. trans, transitional B cells. (b) Principal component analysis (PCA) based on antibody titres, frequencies and GeoMFI of all measured markers (centred and scaled). RBD‐specific parameters were excluded from the analysis. The first component explains 25% of the variation, whereas the second component explains 12.3% of the variation. Each dot represents a donor, and each colour represents a donor group. Dark‐coloured dots show ICU patients. Confidence ellipses for each group are plotted (confidence level set to 95%). (c) Variable correlation plot showing eigenvector‐based coordinates of the top 20 variables in the two‐dimensional space defined by the first two principal components. The relative position of the clinical variables reflects their relationship (positive correlated variables point to the same side of the plot; negative correlated variables point to opposite sides of the plot), while the length of the arrow is proportional to their contribution to the principal components. (d) Relative contribution of the top 10 variables to PC1 (top panel) and PC2 (bottom panel). (a–d) HCs, n = 16; COVT1, n = 25; COVT2, n = 20. (e) Spearman’s correlation analysis of oxygen flow, ferritin and lactate dehydrogenase (LDH) levels in COVID‐19 patients at COVT1 plotted against the Euclidean distance computed using the two first principal components from the PCA of each COVT1 patient to the centroid of the healthy control (HC) group. The HC centroid is computed by averaging PC1 and PC2 for all HCs. Data are presented as individual dots. Dark‐coloured dots show ICU patients. r represents Spearman’s rank‐order correlation.