TABLE 1.
Plasma marker | Healthy pg/ml, (median, IQR) |
Post-Sepsis pg/ml, (median, IQR) |
Post-COVID pg/ml, (median, IQR) |
Between three groups | COVID vs. Healthy | COVID vs. Sepsis | Sepsis vs. Healthy |
Pro-inflammatory | |||||||
Interferon gamma | 10.18 [7.81, 14.13] | 10.24 [9.01, 14.68] | 10.41 [7.50, 18.89] | ns | |||
IL-1B | 0.049 [0.013, 0.160] | 0.290 [0.074, 0.364] | 0.104 [0.053, 0.141] | p < 0.05 | ns | ns | + |
IL-4 | 0.070 [0.044, 0.099] | 0.082 [0.040, 0.112] | 0.076 [0.050, 0.102] | ns | |||
IL-6 | 0.972 [0.696, 1.607] | 2.264 [1.300, 4.058] | 1.934 [1.295, 2.834] | p < 0.0005 | + | ns | + |
IL-10 | 0.654 [0.446, 0.798] | 0.558 [0.442, 0.760] | 0.630 [0.491, 0.941] | ns | |||
TNF alpha | 1.405 [0.754, 2.566] | 1.616 [1.393, 1.938] | 3.146 [2.109, 5.294] | p < 0.0001 | + | + | ns |
Cytokine | |||||||
GM-CSF | 0.634 [0.329, 1.190] | 0.409 [0.260, 1.244] | 0.608 [0.340, 0.975] | ns | |||
IL-17A | 6.366 [2.890, 13.330] | 8.000 [4.521, 26.170] | 8.015 [3.637, 16.320] | ns | |||
IL-12/23p40 | 283.1 [198.6, 344.3] | 408.4 [297.1, 632.7] | 325.0 [197.7, 478.4] | ns | |||
IL-7 | 9.805 [6.689, 11.810] | 7.785 [4.533, 33.360] | 5.023 [3.263, 7.026] | p < 0.005 | – | – | ns |
Chemokine | |||||||
MIP-1beta | 136.8 [110.3, 184.8] | 229.9 [143.3, 336.7] | 132.8 [97.8, 182.4] | p < 0.005 | ns | – | ns |
TARC | 140.5 [112.5, 329.1] | 340.7 [146.4, 550.3] | 122.3 [81.7, 189.7] | p < 0.005 | ns | – | ns |
IP-10 | 585.9 [460.0, 820.1] | 1,077.0 [455.7, 1325.0] | 770.0 [520.3, 1117.0] | ns | |||
MIP-1alpha | 50.39 [35.81, 335.20] | 122.00 [48.67, 274.10] | 45.43 [39.61, 57.28] | ns | |||
MCP-1 | 125.8 [184.5, 245.2] | 208.5 [178.7, 328.8] | 261.3 [214.7, 318.1] | ns | |||
MCP-4 | 119.2 [97.4, 155.5] | 236.7 [125.6, 309.0] | 134.3 [114.1, 184.2] | ns | |||
Angiogenesis | |||||||
VEGF-A | 48.31 [34.02, 83.91] | 76.94 [51.08, 152.20] | 49.01 [30.09, 73.96] | ns | |||
VEGF-C | 1129 [921, 1482] | 1716 [1102, 2974] | 1063 [782, 1668] | ns | |||
VEGF-D | 726.8 [554.9, 944.3] | 861.1 [702.8, 1127.0] | 819.2 [684.4, 1092.0] | ns | |||
Tie-2* | 3434 ± 300 | 3245 ± 302 | 3923 ± 784 | p < 0.005 | + | + | ns |
Flt-1 | 93.49 [82.81, 109.60] | 97.10 [65.96, 113.80] | 124.40 [97.24, 157.90] | p < 0.005 | + | + | ns |
PIGF | 3.010 [2.548, 3.177] | 3.968 [2.577, 5.888] | 4.260 [3.593, 5.360] | p < 0.0001 | + | ns | + |
bFGF | 22.17 [14.03, 41.34] | 49.59 [9.19, 117.00] | 2.06 [1.38, 4.23] | p < 0.0001 | – | – | ns |
Vascular injury | |||||||
SAA | 1266741 [832641, 2592227] | 2616109 [1540017, 8354912] | 2720091 [1382324, 5395892] | p < 0.02 | + | ns | ns |
CRP | 633598 [418901, 1559464] | 3550592 [1632105, 6856682] | 2253276 [1117127, 5794106] | p < 0.005 | + | ns | + |
VCAM-1 | 493133 [457268, 538105] | 657406 [491048, 878164] | 552729 [434409, 729479] | p < 0.05 | ns | ns | + |
ICAM-1 | 305599 [253191, 381896] | 576237 [449555, 743289] | 385068 [287088, 480021] | p < 0.005 | ns | – | + |
Five different MSD assay panels, each containing a set of mediators as shown, were used: (i) pro-inflammatory panel, (ii) cytokine panel (cytokines related to immune differentiation and growth), (iii) chemokine panel (cytokines related to monocyte chemotaxis), (iv) angiogenic, and (v) vascular injury panels (related to vascular injury and repair). Between-group analysis was performed by the Kruskal-Wallis test. Values are given as median and interquartile range (25th centile, 75th centile). Statistical significance was achieved if p < 0.05 and p < Benjamini-Hochberg critical value, with an FDR-adjusted q-value of 0.05. Where the three-way comparison between groups was significant, pairwise analysis was performed (Dunn test) for “post-COVID vs. healthy,” “post-COVID vs. post-sepsis,” and “post-sepsis vs. healthy.” + denotes significantly higher in 1st vs. 2nd group; – denotes significantly lower in 1st vs. 2nd group. Individual markers shown in bold and italic denote “COVID different from healthy control and different from post-Sepsis.” * for SAA, values are given as mean ± SD, and ANOVA test was used for between-group analysis (and Tukey’s test for pairwise comparisons) as data were normally distributed.