Table 3.
Open in new tab

Associations Between Concurrent Viremia Events and Clinical Outcome

Cox ModelICU Discharge
(CSHR)		Death in ICU
(CSHR)		Death in ICU
(SHR)
Concurrent cytomegalovirus and Epstein–Barr virus viremia
Crude model with adjustment for
 time-varying onset of viremia0.69 (0.44–1.08)2.54 (1.43–4.50)3.48 (1.60–7.58)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.83 (0.54–1.27)2.44 (1.33–4.49)3.17 (1.41–7.13)
Concurrent cytomegalovirus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia1.14 (0.72–1.79)2.52 (1.24–5.11)2.67 (0.95–7.49)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab1.15 (0.71–1.87)2.39 (1.15–4.98)2.51 (0.88–7.18)
Concurrent Epstein–Barr virus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia0.78 (0.54–1.12)1.81 (1.06–3.08)2.16 (1.11–4.23)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.87 (0.61–1.24)1.55 (0.87–2.77)1.87 (0.91–3.86)
Cox ModelICU Discharge
(CSHR)		Death in ICU
(CSHR)		Death in ICU
(SHR)
Concurrent cytomegalovirus and Epstein–Barr virus viremia
Crude model with adjustment for
 time-varying onset of viremia0.69 (0.44–1.08)2.54 (1.43–4.50)3.48 (1.60–7.58)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.83 (0.54–1.27)2.44 (1.33–4.49)3.17 (1.41–7.13)
Concurrent cytomegalovirus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia1.14 (0.72–1.79)2.52 (1.24–5.11)2.67 (0.95–7.49)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab1.15 (0.71–1.87)2.39 (1.15–4.98)2.51 (0.88–7.18)
Concurrent Epstein–Barr virus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia0.78 (0.54–1.12)1.81 (1.06–3.08)2.16 (1.11–4.23)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.87 (0.61–1.24)1.55 (0.87–2.77)1.87 (0.91–3.86)

Abbreviations: CSHR, cause-specific hazard ratio; ICU, intensive care unit; SHR, Subdistribution Hazard Ratio.

In each of the 3 different Cox regression models, all 329 patients were included, but in every model a different combination of viremia was assessed as follows: combined cytomegalovirus (CMV) and Epstein–Barr virus (EBV) viremia (n = 38), CMV and human herpesvirus 6 (HHV-6) (n = 22), or EBV and HHV-6 (n = 54), respectively.

Data are presented as hazard ratios with 95% confidence intervals. CSHR estimates the direct effect of viremia on clinical outcome (ie, ICU discharge or death). The subdistribution hazard ratio is a summary measure of both separate cause-specific hazards and estimates the overall risk of dying from viremia while taking into account the competing event of discharge alive from the ICU.

aAdjusted for Acute Physiology and Chronic Health Evaluation (APACHE) IV score, prior ICU admission during the hospital stay, surgical reason for admission, and Charlson comorbidity index

bAdjusted for time-dependent covariables, including sequential organ failure assessment score (using a 48-hour time lag to avoid statistical overcorrection) and use of high-dose corticosteroid therapy (defined by a daily hydrocortisone dose of ≥250 mg or equivalent).

Table 3.
Open in new tab

Associations Between Concurrent Viremia Events and Clinical Outcome

Cox ModelICU Discharge
(CSHR)		Death in ICU
(CSHR)		Death in ICU
(SHR)
Concurrent cytomegalovirus and Epstein–Barr virus viremia
Crude model with adjustment for
 time-varying onset of viremia0.69 (0.44–1.08)2.54 (1.43–4.50)3.48 (1.60–7.58)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.83 (0.54–1.27)2.44 (1.33–4.49)3.17 (1.41–7.13)
Concurrent cytomegalovirus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia1.14 (0.72–1.79)2.52 (1.24–5.11)2.67 (0.95–7.49)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab1.15 (0.71–1.87)2.39 (1.15–4.98)2.51 (0.88–7.18)
Concurrent Epstein–Barr virus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia0.78 (0.54–1.12)1.81 (1.06–3.08)2.16 (1.11–4.23)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.87 (0.61–1.24)1.55 (0.87–2.77)1.87 (0.91–3.86)
Cox ModelICU Discharge
(CSHR)		Death in ICU
(CSHR)		Death in ICU
(SHR)
Concurrent cytomegalovirus and Epstein–Barr virus viremia
Crude model with adjustment for
 time-varying onset of viremia0.69 (0.44–1.08)2.54 (1.43–4.50)3.48 (1.60–7.58)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.83 (0.54–1.27)2.44 (1.33–4.49)3.17 (1.41–7.13)
Concurrent cytomegalovirus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia1.14 (0.72–1.79)2.52 (1.24–5.11)2.67 (0.95–7.49)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab1.15 (0.71–1.87)2.39 (1.15–4.98)2.51 (0.88–7.18)
Concurrent Epstein–Barr virus and human herpesvirus 6 viremia
Crude model with adjustment for
 time-varying onset of viremia0.78 (0.54–1.12)1.81 (1.06–3.08)2.16 (1.11–4.23)
Multivariable model with adjustment for
 time-varying onset of viremia
 severity of illness at ICU admissiona
 evolution of disease prior to viremiab0.87 (0.61–1.24)1.55 (0.87–2.77)1.87 (0.91–3.86)

Abbreviations: CSHR, cause-specific hazard ratio; ICU, intensive care unit; SHR, Subdistribution Hazard Ratio.

In each of the 3 different Cox regression models, all 329 patients were included, but in every model a different combination of viremia was assessed as follows: combined cytomegalovirus (CMV) and Epstein–Barr virus (EBV) viremia (n = 38), CMV and human herpesvirus 6 (HHV-6) (n = 22), or EBV and HHV-6 (n = 54), respectively.

Data are presented as hazard ratios with 95% confidence intervals. CSHR estimates the direct effect of viremia on clinical outcome (ie, ICU discharge or death). The subdistribution hazard ratio is a summary measure of both separate cause-specific hazards and estimates the overall risk of dying from viremia while taking into account the competing event of discharge alive from the ICU.

aAdjusted for Acute Physiology and Chronic Health Evaluation (APACHE) IV score, prior ICU admission during the hospital stay, surgical reason for admission, and Charlson comorbidity index

bAdjusted for time-dependent covariables, including sequential organ failure assessment score (using a 48-hour time lag to avoid statistical overcorrection) and use of high-dose corticosteroid therapy (defined by a daily hydrocortisone dose of ≥250 mg or equivalent).

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