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
Publication date
2018-12-18
Authors
van de Groep, Kirsten
Nierkens, Stefan
Cremer, Olaf L
Peelen, Linda M.
Klein Klouwenberg, Peter M C
Schultz, Marcus J.
Hack, Erik
Van Der Poll, Tom
Bonten, Marc
Ong, David S Y
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Document Type
Article
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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.
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
Citation
Van De Groep, K, Nierkens, S, Cremer, O L, Peelen, L M, Klein Klouwenberg, P M C, Schultz, M J, Hack, C E, Van Der Poll, T, Bonten, M J M, Ong, D S Y, De Beer, F M, Bos, L D J, Glas, G J, Hoogendijk, A J, Van Hooijdonk, R T M, Horn, J, Huson, M A, Juffermans, N P, Schouten, L R A, Scicluna, B, Straat, M, Van Vught, L A, Wieske, L, Wiewel, M A, Witteveen, E, Frencken, J F, Van De Groep, K, Koster-Brouwer, M E, Varkila, M R J & Verboom, D M 2018, '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', Critical Care, vol. 22, no. 1, 348. https://doi.org/10.1186/s13054-018-2261-0