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Critical Care
Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

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

Authors: Kirsten van de Groep, Stefan Nierkens, Olaf L. Cremer, Linda M. Peelen, Peter M. C. Klein Klouwenberg, Marcus J. Schultz, C. Erik Hack, Tom van der Poll, Marc J. M. Bonten, David S. Y. Ong, on behalf of the MARS consortium

Published in: Critical Care | Issue 1/2018

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Abstract

Background

Cytomegalovirus (CMV) reactivation in previously immunocompetent critically ill patients is associated with increased mortality, which has been hypothesized to result from virus-induced immunomodulation. Therefore, we studied the effects of CMV reactivation on the temporal course of host response biomarkers in patients with sepsis.

Methods

In this matched cohort study, each sepsis patient developing CMV reactivation between day 3 and 17 (CMV+) was compared with one CMV seropositive patient without reactivation (CMVs+) and one CMV seronegative patient (CMVs−). CMV serostatus and plasma loads were determined by enzyme-linked immunoassays and real-time polymerase chain reaction, respectively. Systemic interleukin-6 (IL-6), IL-8, IL-18, interferon-gamma–induced protein-10 (IP-10), neutrophilic elastase, IL-1 receptor antagonist (RA), and IL-10 were measured at five time points by multiplex immunoassay. The effects of CMV reactivation on sequential concentrations of these biomarkers were assessed in multivariable mixed models.

Results

Among 64 CMV+ patients, 45 could be matched to CMVs+ or CMVs− controls or both. The two baseline characteristics and host response biomarker levels at viremia onset were similar between groups. CMV+ patients had increased IP-10 on day 7 after viremia onset (symmetric percentage difference +44% versus −15% when compared with CMVs+ and +37% versus +4% when compared with CMVs−) and decreased IL-1RA (−41% versus 0% and −49% versus +10%, respectively). However, multivariable analyses did not show an independent association between CMV reactivation and time trends of IL-6, IP-10, IL-10, or IL-1RA.

Conclusion

CMV reactivation was not independently associated with changes in the temporal trends of host response biomarkers in comparison with non-reactivating patients. Therefore, these markers should not be used as surrogate clinical endpoints for interventional studies evaluating anti-CMV therapy.
Appendix
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Metadata
Title
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
Authors
Kirsten van de Groep
Stefan Nierkens
Olaf L. Cremer
Linda M. Peelen
Peter M. C. Klein Klouwenberg
Marcus J. Schultz
C. Erik Hack
Tom van der Poll
Marc J. M. Bonten
David S. Y. Ong
on behalf of the MARS consortium
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-2261-0

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