Biomarkers possibly associated with the SEID diagnostic criteria
| Patients with CFS, baseline | Difference/ OR | 95% CI of difference/OR | P value, not adjusted | P value, adjusted* | |||
| SEID-negative (n=69) | SEID-positive (n=45) | ||||||
| Cardiovascular variables, supine | |||||||
| Heart rate, beats/min, mean (SD) | 69.5 (9.0) | 73.7 (13.1) | 4.21 | −0.23 to 8.64 | 0.063 | ||
| MAP, mm Hg, mean (SD) | 78.7 (7.9) | 79.2 (9.2) | 0.54 | −2.66 to 3.73 | 0.740 | ||
| TPRI, mm Hg/L/min/m2 ×10−3, mean (SD) | 8.70 (2.12) | 9.39 (16.6) | 0.69 | −0.05 to 1.43 | 0.067 | ||
| LFnuRRI, normalised units, mean (SD) | 38.7 (16.2) | 46.1 (13.0) | 7.43 | 1.72 to 13.1 | 0.011 | 0.104 | |
| HFnuRRI, normalised units, mean (SD) | 61.3 (16.3) | 53.9 (13.0) | −7.39 | −13.1 to −1.67 | 0.012 | 0.106 | |
| LFabsRRI, ms2, median (IQR) | 632 (805) | 451 (774) | −182 | −516 to 136 | 0.159 | ||
| HFabsRRI, ms2, median (IQR) | 1016 (1974) | 495 (1662) | −521 | −1239 to 22 | 0.014 | 0.051 | |
| LF:HF ratio, median (IQR) | 0.63 (0.56) | 0.92 (0.88) | 0.29 | 0.05 to 0.52 | 0.008 | 0.082 | |
| Cardiovascular variables, delta values† | |||||||
| Heart rate, beats/min, mean (SD) | 5.19 (4.39) | 4.60 (3.22) | −0.58 | −2.09 to 0.93 | 0.418 | ||
| MAP, mm Hg, mean (SD) | 1.02 (4.02) | 1.32 (3.43) | 0.30 | −1.14 to 1.74 | 0.684 | ||
| TPRI, mm Hg/L/min/m2 ×10−3, mean (SD) | 6.24 (8.09) | 6.46 (8.63) | 0.021 | −0.29 to 0.34 | 0.895 | ||
| LFnuRRI, normalised units, mean (SD) | 9.22 (10.1) | 5.32 (12.5) | −3.90 | −8.12 to 0.32 | 0.083 | ||
| HFnuRRI, normalised units, mean (SD) | −9.19 (10.1) | −5.32 (12.5) | 3.87 | −0.55–8.28 | 0.086 | ||
| LFabsRRI, ms2, median (IQR) | −94.3 (428) | −101 (316) | −7.2 | −126 to 166 | 0.739 | ||
| HFabsRRI, ms2, median (IQR) | −355 (961) | −153 (815) | 202 | −103 to 539 | 0.075 | ||
| LF:HF ratio, median (IQR) | 0.24 (0.66) | 0.21 (0.80) | −0.02 | −0.43 to 0.29 | 0.092 | ||
| Infectious variables | |||||||
| Anti-EBV EBNA IgG, n (%) | Negative | 32 (49.2) | 25 (56.8) | 0.74 | 0.34 to 1.59 | 0.436 | |
| Positive | 33 (50.8) | 19 (43.2) | |||||
| Anti-EBV VCA IgM, n (%) | Negative | 67 (98.5) | 43 (95.6) | 0.36 | 0.37 to 35.4 | 0.562 | |
| Positive | 1 (1.5) | 2 (4.4) | |||||
| Anti-EBV VCA IgG, n (%) | Negative | 29 (65.9) | 21 (67.7) | 0.92 | 0.35 to 2.45 | 0.868 | |
| Positive | 15 (34.1) | 10 (32.3) | |||||
| Anti-CMV IgM, n (%) | Negative | 67 (100) | 45 (100) | NA | |||
| Positive | 0 (0) | 0 (0) | |||||
| Anti-CMV IgG, n (%) | Negative | 38 (55.9) | 24 (53.3) | 1.11 | 0.52 to 2.36 | 0.790 | |
| Positive | 30 (44.1) | 21 (46.7) | |||||
| Inflammatory variables | |||||||
| Serum hsCRP, mg/L, median (IQR) | 0.44 (0.97) | 0.46 (0.62) | 0.02 | −0.25 to 0.21 | 0.526 | ||
| Serum IL-1β, pg/mL, median (IQR) | 2.03 (2.12) | 2.31 (2.31) | 0.28 | −0.92 to 1.06 | 0.620 | ||
| Serum IL-6, pg/mL, median (IQR) | 6.56 (5.54) | 7.39 (7.29) | 0.83 | −1.66 to 3.00 | 0.481 | ||
| Serum IL-10, pg/mL, median (IQR) | 3.49 (3.35) | 4.07 (6.68) | 0.59 | −1.25 to 3.16 | 0.936 | ||
| Serum TNF, pg/mL, median (IQR) | 45.5 (39.1) | 46.8 (46.1) | 1.34 | −13.3 to 15.5 | 0.674 | ||
| Neuroendocrine variables | |||||||
| Plasma norepinephrine, pmol/L, mean (SD) | 1972 (722) | 2017 (893) | 45 | −258 to 348 | 0.770 | ||
| Plasma epinephrine, pmol/L, mean (SD) | 316 (104) | 323 (125) | 6.36 | −37.4 to 50.1 | 0.774 | ||
| Plasma cortisol, nmol/L, mean (SD) | 345 (135) | 400 (156) | 55 | −0.06 to 110 | 0.050 | ||
| Urine norepinephrine:creatinine ratio, pmol/mmol, mean (SD) | 13.0 (4.80) | 12.4 (4.23) | −0.55 | −2.31 to 1.21 | 0.539 | ||
| Urine epinephrine:creatinine ratio, pmol/mmol, median (IQR) | 1.22 (1.27) | 1.27 (1.06) | 0.06 | −0.40 to 0.59 | 0.948 | ||
| Urine cortisol:creatinine ratio, nmol/mmol, median (IQR) | 3.61 (2.56) | 3.16 (3.45) | −0.45 | −1.69 to 0.57 | 0.451 | ||
| Cognitive variables | |||||||
| Digit span test, sum score, mean (SD) | 14.7 (3.70) | 13.2 (2.92) | −1.51 | −2.81 to −0.21 | 0.023 | ||
| D-KEFS conditions 1 and 2 mean, s, mean (SD) | 29.7 (4.85) | 30.9 (4.67) | 1.20 | −0.65 to 3.04 | 0.201 | ||
| D-KEFS condition 3, s, mean (SD) | 57.3 (12.3) | 61.0 (12.5) | 3.69 | −1.01 to 8.39 | 0.123 | ||
| HVLT 1–3, sum score, mean (SD) | 27.8 (3.94) | 26.4 (4.14) | −1.33 | −2.86 to 0.19 | 0.086 | ||
P values are based on Χ2 test, Fisher’s exact test, Student’s t-test or Mann-Whitney’s test, as appropriate. Due to multiple comparisons, the level of significance is considered equal to 0.05/44=0.00114.
*Multiple linear regression models, adjusting for MFQ, CFQ total score and steps per day.
†Response to 20° head-up tilt (delta values).
abs, absolute; CFQ, Chalder Fatigue Questionnaire; D-KEFS, Delis-Kaplan Executive Function System; hsCRP, high-sensitivity C-reactive protein; HF, high frequency; HVLT, Hopkins Verbal Learning Test; IL, interleukin; LF, low frequency; MAP, mean arterial pressure; MFQ, Mood and Feelings Questionnaire; NA, not applicable; nu, normalised units; RRI, RR-interval; SEID, systemic exertion intolerance disease; TNF, tumour necrosis factor; TPRI, Total Peripheral Resistance Index.