Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients.

Methods

We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients.

Results

The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135–2.417). This effect was observed independent of age ( p = 0.010; HR, 1.673; 95% CI 1.131–2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075–5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients.

Conclusion

We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-023-04713-1.

Related collections

Most cited references 44

Record: found
Abstract: found
Article: not found

Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection.

Michael J. Cannon, D. Scott Schmid, Terri Hyde (2010)

Cytomegalovirus establishes a lifelong latent infection following primary infection that can periodically reactivate with shedding of infectious virus. Primary infection, reactivation and reinfection during pregnancy can all lead to in utero transmission to the developing fetus. Congenital CMV infections are a major cause of permanent hearing loss and neurological impairment. In this literature review, we found that CMV infection was relatively common among women of reproductive age, with seroprevalence ranging from 45 to 100%. CMV seroprevalence tended to be highest in South America, Africa and Asia and lowest in Western Europe and United States. Within the United States, CMV seroprevalence showed substantial geographic variation as well, differing by as much as 30 percentage points between states, though differences might be explained by variation in the types of populations sampled. Worldwide, seroprevalence among non-whites tended to be 20-30 percentage points higher than that of whites (summary prevalence ratio (PR) = 1.59, 95% confidence interval (CI) = 1.57-1.61). Females generally had higher seroprevalences than males, although in most studies the differences were small (summary PR = 1.13, 95% CI = 1.11-1.14). Persons of lower socioeconomic status were more likely to be CMV seropositive (summary PR = 1.33, 95% CI = 1.32-1.35). Despite high seroprevalences in some populations, a substantial percentage of women of reproductive age are CMV seronegative and thus at risk of primary CMV infection during pregnancy. Future vaccine or educational campaigns to prevent primary infection in pregnant women may need to be tailored to suit the needs of different populations.

0 comments Cited 247 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Variation in the human immune system is largely driven by non-heritable influences.

Petter Brodin, Vladimir Jojic, Tianxiang Gao … (2015)

There is considerable heterogeneity in immunological parameters between individuals, but its sources are largely unknown. To assess the relative contribution of heritable versus non-heritable factors, we have performed a systems-level analysis of 210 healthy twins between 8 and 82 years of age. We measured 204 different parameters, including cell population frequencies, cytokine responses, and serum proteins, and found that 77% of these are dominated (>50% of variance) and 58% almost completely determined (>80% of variance) by non-heritable influences. In addition, some of these parameters become more variable with age, suggesting the cumulative influence of environmental exposure. Similarly, the serological responses to seasonal influenza vaccination are also determined largely by non-heritable factors, likely due to repeated exposure to different strains. Lastly, in MZ twins discordant for cytomegalovirus infection, more than half of all parameters are affected. These results highlight the largely reactive and adaptive nature of the immune system in healthy individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

0 comments Cited 207 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial

Dirk Schädler, Christine Pausch, Daniel Heise … (2017)

Objective We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. Methods This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. Results 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). Conclusions In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

0 comments Cited 134 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

B. Koos: Bjoern.Koos@rub.de

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 31 October 2023

Publication date PMC-release: 31 October 2023

Publication date Collection: 2023

Volume: 27

Electronic Location Identifier: 417

Affiliations

[1 ]Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, ( https://ror.org/024j3hn90) Bochum, Germany

[2 ]Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn, ( https://ror.org/01xnwqx93) Bonn, Germany

[3 ]Medizinisches Proteom-Center, Ruhr-University Bochum, ( https://ror.org/04tsk2644) 44801 Bochum, Germany

[4 ]Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr University Bochum, ( https://ror.org/04tsk2644) 44801 Bochum, Germany

[5 ]GRID grid.411067.5, ISNI 0000 0000 8584 9230, Klinik für Anästhesiologie, , Intensivmedizin und Schmerztherapie, ; Klinikum Westfalen, Dortmund, Germany

[6 ]Department of Anaesthesiology and Operative Intensive Care Medicine, University of Witten/Herdecke, Cologne Merheim Medical School, ( https://ror.org/00yq55g44) Cologne, Germany

[7 ]Department of Anesthesiology, Surgical Intensive Care, Emergency and Pain Medicine, Ruhr-University Bochum, ( https://ror.org/04tsk2644) Klinikum Herford, Herford, Germany

[8 ]Department of Anesthesiology and Intensive Care Medicine, AMEOS-Klinikum Halberstadt, Halberstadt, Germany

[9 ]Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie, Universitätsklinikum Münster, ( https://ror.org/01856cw59) Münster, Germany

[10 ]GRID grid.512807.9, ISNI 0000 0000 9874 2651, Marien Hospital Herne, , Universitätsklinikum der Ruhr-Universität Bochum, ; Bochum, Germany

[11 ]Center for Translational Medicine, Medical Clinic I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, ( https://ror.org/04tsk2644) Herne, Germany

[12 ]Department of Molecular and Medical Virology, Ruhr University Bochum, ( https://ror.org/04tsk2644) 44801 Bochum, Germany

[13 ]Institute for Virology, University Hospital Essen, University of Duisburg-Essen, ( https://ror.org/04mz5ra38) Essen, Germany

[14 ]Knappschaft Kliniken GmbH, Recklinghausen, Germany

[15 ]GRID grid.465549.f, ISNI 0000 0004 0475 9903, Center for Artficial Intelligence, Medical Informatics and Data Science, , University Hospital Knappschaftskrankenhaus Bochum, ; Bochum, Germany

Article

Publisher ID: 4713

DOI: 10.1186/s13054-023-04713-1

PMC ID: 10619294

PubMed ID: 37907989

SO-VID: fefdbc94-1cde-4f4b-9d70-d42d08f4eaba

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 1 August 2023

Date accepted : 26 October 2023

Funding

Funded by: European Regional Development Fund of the European Union

Award ID: SepsisDataNet

Award Recipient : T. Bracht M. Bazzi B. Sitek K. Marcus M. Eisenacher B. Ellger M. Anft N. Babel M. Adamzik B. Koos

Funded by: MSD

Funded by: Ruhr-Universität Bochum (1007)

Open Access :

Open Access funding enabled and organized by Projekt DEAL.

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: sepsis,hcmv latency,inflammatory biomarker,mortality prediction

Data availability:

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: sepsis, hcmv latency, inflammatory biomarker, mortality prediction

Comments

Comment on this article

scite_

Cited by 5

See all cited by

Most referenced authors 612

See all reference authors

Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis

Read this article at

Abstract

Background

Methods

Results

Conclusion

Supplementary Information

Related collections

Irish Journal of Paramedicine

Most cited references 44

Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection.

Variation in the human immune system is largely driven by non-heritable influences.

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 791

Cited by 5

Most referenced authors 612