Effect of cytomegalovirus reactivation on the time course of systemic host response biomarkers in previously immunocompetent critically ill patients with sepsis: a matched cohort study

Table 3 Multivariable generalized mixed model analyses relating levels and trends of four host response biomarkers to cytomegalovirus reactivation

Marker	Baseline level (t = −2)	Effect reactivation on level	P value	Time trend per day	P value	Effect reactivation on time trend	P value
Primary comparison^a
IL-6	5.50 (3.31–7.68)	−0.58 (−1.27–0.10)	0.03	−0.23 (−0.38 – −0.08) ^c	< 0.001	0.07 (−0.02–0.16)	0.06
IP-10	7.23 (5.71–8.72)	−0.31 (−0.80–0.18)	0.10	−0.03 (−0.09–0.03)	0.18	0.07 (−0.01–0.16)	0.03
IL-10	2.44 (0.33–4.45)	−0.02 (−0.78–0.74)	0.94	−0.09 (−0.17 – −0.03)	0.007	0.07 (−0.02–0.18)	0.10
IL-1RA	6.12 (3.77–8.47)	−0.17 (−0.93–0.59)	0.57	−0.08 (−0.16–0.00)	0.01	0.02 (−0.09–0.14)	0.62
Secondary comparison^b
IL-6	4.83 (2.53–7.15)	−0.34 (−1.02–0.34)	0.21	−0.15 (−0.27 – −0.02) ^c	0.003	0.01 (−0.07–0.08)	0.82
IP-10	6.00 (4.54–7.44)	0.14 (−0.34–0.62)	0.45	0.02 (−0.04–0.07)	0.45	0.03 (−0.06–0.12)	0.36
IL-10	1.22 (−0.60–3.08)	0.17 (−0.38–0.72)	0.43	−0.04 (−0.11–0.01)	0.06	0.02 (−0.07–0.12)	0.50
IL-1RA	4.97 (2.31–7.64)	0.06 (−0.76–0.89)	0.85	0.00 (−0.08–0.09)	0.91	−0.07 (−0.19–0.05)	0.15

Abbreviations: CMV cytomegalovirus, IL interleukin, IP-10 interferon-gamma induced protein-10, RA receptor antagonist
Data are presented as coefficient of the model (99% confidence interval) derived from generalized mixed model analyses. Age and Sequential Organ Failure Assessment (SOFA) score at t = 0 (day of viremia onset) were included as confounders in each model because a range was used as matching criteria for these co-variables. Baseline levels were derived from intercept estimates, and the effect of reactivation on the time trend was assessed by an interaction term between time and CMV reactivation
^aIn the primary comparison, patients with CMV reactivation were compared with matched CMV seropositive patients without reactivation
^bIn the secondary comparison, patients with CMV reactivation were compared with matched CMV seronegative patients
^cFinal models for IL-6 included a polynomial time effect; the estimates for t² were 0.01 (0.00–0.03) in the primary comparison and 0.01 (0.00–0.03) in the secondary comparison

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