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
Van De Groep, K.; Nierkens, Stefan; Cremer, Olaf L.; Peelen, Linda M.; Klein Klouwenberg, Peter M.C.; Schultz, Marcus J.; Hack, C. Erik; Van Der Poll, Tom; Bonten, Marc J.M.; Ong, David S.Y.; De Beer, Friso M.; Bos, Lieuwe D.J.; Glas, Gerie J.; Hoogendijk, Arie J.; Van Hooijdonk, Roosmarijn T.M.; Horn, Janneke; Huson, Mischa A.; Juffermans, Nicole P.; Schouten, Laura R.A.; Scicluna, Brendon; Straat, Marleen; Van Vught, Lonneke A.; Wieske, Luuk; Wiewel, Maryse A.; Witteveen, Esther; Frencken, Jos F.; Van De Groep, K.; Koster-Brouwer, Maria E.; Varkila, Meri R.J.; Verboom, Diana M.
(2018) Critical Care, volume 22, issue 1
(Article)
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,
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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.
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Keywords: Aged, Biomarkers/analysis, Chemokine CXCL10/analysis, Chi-Square Distribution, Cohort Studies, Critical Illness, Cytomegalovirus/immunology, Cytomegalovirus Infections/blood, Female, Humans, Immunity, Humoral/physiology, Intensive Care Units/organization & administration, Interleukin 1 Receptor Antagonist Protein/analysis, Interleukin-10/analysis, Interleukin-6/analysis, Male, Middle Aged, Sepsis/immunology, Virus Activation/physiology, Cytomegalovirus, Reactivation, Critically ill, Inflammation, Host response, Critical Care and Intensive Care Medicine, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 1364-8535
Publisher: Springer Science + Business Media
Note: Funding Information: This work was supported by the Center for Translation Molecular Medicine (http://www.ctmm.nl), project MARS (grant 041–201). The sponsor did not play a role in the design and conduct of the study (including collection, management, analysis, and interpretation of the data) or the preparation of the manuscript (including review or approval of the manuscript or decision to submit the manuscript for publication). Publisher Copyright: © 2018 The Author(s).
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