Table 2.
Relationship of Outcomes at 18 Months With Cytokine Levels and Inflammatory Markers Over Time
| 18-mo cognitive symptom present (N = 76) | 18-mo cognitive symptom absent (N = 203) | p Value | 18-mo any neurologic symptom present (N = 160) | No 18-mo neurologic symptoms (N = 119) | p Value | 18-mo PROMIS physical health T-score<45 (N = 141) | 18-mo PROMIS physical health T-score≥45 (N = 133) | p Value | 18-mo PROMIS mental health T-score<45 (N = 66) | 18-mo PROMIS mental health T-score≥45 (N = 205) | p Value | |
| Cytokine area under the curve (baseline, day 1, 18 months) | ||||||||||||
| IL-1β (pg/mL) | 3,267 | 3,267 | 0.706 | 3,627 | 3,627 | 0.924 | 3,627 | 3,627 | 0.831 | 3,627 | 3,627 | 0.232 |
| IL-10 (pg/mL) | 3,491 | 3,701 | 0.711 | 2,628 | 3,775 | 0.903 | 2,909 | 3,775 | 0.276 | 2,848 | 3,812 | 0.255 |
| IL-12 (pg/mL) | 1,060 | 1,060 | 0.522 | 1,060 | 1,060 | 0.691 | 1,060 | 1,060 | 0.928 | 1,060 | 1,060 | 0.619 |
| IL-13 (pg/mL) | 949 | 949 | 0.352 | 949 | 949 | 0.839 | 949 | 949 | 0.925 | 949 | 949 | 0.643 |
| IL-2 (pg/mL) | 1,172 | 1,172 | 0.955 | 1,172 | 1,172 | 0.736 | 1,172 | 1,172 | 0.632 | 1,172 | 1,172 | 0.535 |
| IL-2sR (pg/mL) | 467,704 | 524,280 | 0.348 | 471,933 | 527,632 | 0.293 | 475,484 | 520,929 | 0.700 | 401,731 | 526,589 | 0.050 |
| IL-4 (pg/mL) | 1,228 | 1,228 | 0.602 | 1,228 | 1,228 | 0.597 | 1,228 | 1,228 | 0.495 | 1,228 | 1,228 | 0.548 |
| IL-5 (pg/mL) | 1,172 | 1,172 | 0.572 | 1,172 | 1,172 | 0.819 | 1,172 | 1,172 | 0.965 | 1,172 | 1,172 | 0.786 |
| IL-6 (pg/mL) | 1786 | 1,479 | 0.883 | 1,398 | 1955 | 0.656 | 1761 | 1,401 | 0.581 | 1,398 | 1,508 | 0.650 |
| IL-8 (pg/mL) | 1,674 | 1,674 | 0.549 | 1,674 | 1,674 | 0.922 | 1,674 | 1,674 | 0.922 | 1,674 | 1,674 | 0.782 |
| INF-γ (pg/mL) | 2,344 | 2,344 | 0.607 | 2,344 | 2,344 | 0.776 | 2,344 | 2,344 | 0.915 | 2,344 | 2,344 | 0.745 |
| TNF-α (pg/mL) | 1,450 | 1,367 | 0.841 | 1,369 | 1,367 | 0.466 | 1,284 | 1,534 | 0.489 | 1,088 | 1,453 | 0.366 |
| Inflammatory laboratory area under the curve (baseline, day 3, day 7, 18 months) | ||||||||||||
| D-dimer (ng/mL) | 219,887 | 203,875 | 0.806 | 232,739 | 188,342 | 0.308 | 208,350 | 193,120 | 0.963 | 253,614 | 194,160 | 0.334 |
| Fibrinogen (mg/dL) | 250,470 | 137,879 | 0.388 | 246,023 | 238,233 | 0.860 | 241,575 | 245,021 | 0.223 | 229,673 | 254,218 | 0.657 |
| LDH (U/L) | 175,220 | 150,614 | 0.040 | 164,552 | 144,299 | 0.076 | 150,614 | 265,339 | 0.187 | 170,585 | 162,408 | 0.239 |
| Ferritin (ng/mL) | 240,887 | 194,511 | 0.360 | 227,210 | 194,511 | 0.406 | 175,579 | 240,333 | 0.086 | 182,854 | 215,155 | 0.484 |
| CRP (mg/L) | 4,327 | 4,136 | 0.727 | 4,143 | 4,452 | 0.336 | 4,615 | 4,279 | 0.604 | 2,681 | 4,452 | 0.107 |
| Neutrophil counta (103/µL) | 3,114 | 3,046 | 0.842 | 3,092 | 3,098 | 0.650 | 3,046 | 3,092 | 0.494 | 3,611 | 3,012 | 0.022 |
Median Area under the curve (AUC) for each serum cytokine (measured at baseline, day 1, and 18 months post-randomization), and serum inflammatory marker (measured at baseline, day 3, day 7, and 18 months post-randomization) compared between those with or without secondary outcomes of 18-mo neurologic symptoms, PROMIS Global Physical Health T-score<45, and PROMIS Global Mental Health T-score<45.
a
Measured at baseline, 3 days postrandomization and 18 months postrandomization; LDH = lactate dehydrogenase; CRP = C-reactive peptide. Significance after Bonferroni correction for multiple comparisons was calculated as p ≤ 0.003.