Reactivation of Epstein-Barr virus among intensive care patients: a prospective observational study.

Cytomegalovirus Epstein–Barr virus Herpesvirus Intensive care medicine Viral reactivation

Journal

Intensive care medicine
ISSN: 1432-1238
Titre abrégé: Intensive Care Med
Pays: United States
ID NLM: 7704851

Informations de publication

Date de publication:
Mar 2024
Historique:
received: 11 10 2023
accepted: 02 02 2024
pubmed: 4 3 2024
medline: 4 3 2024
entrez: 4 3 2024
Statut: ppublish

Résumé

Herpesvirus reactivation has been documented among patients in the intensive care unit (ICU) and is associated with increased morbidity and mortality, particularly for cytomegalovirus (CMV). Epstein-Barr virus (EBV) has been poorly studied despite >95% of the population being seropositive. Our preliminary study suggested an association between EBV reactivation and increased morbidity and mortality. This study aimed to investigate this association among patients admitted to the ICU. In this multicenter prospective study, polymerase chain reaction was performed to quantify EBV in patients upon ICU admission and then twice a week during their stay. Follow-up was 90 days. The study included 129 patients; 70 (54.3%) had EBV reactivation. On day 90, there was no difference in mortality rates between patients with and without reactivation (25.7% vs 15.3%, p = 0.22). Patients with EBV reactivation at admission had increased mortality compared with those without reactivation and those with later reactivation. EBV reactivation was associated with increased morbidity. Patients with EBV reactivation had fewer ventilator-free days at day 28 than those without reactivation (18 [1-22] vs. 21 days [5-26], p = 0.037) and a higher incidence of acute respiratory distress syndrome (34.3% vs. 17%, p = 0.04), infections (92.9% vs. 78%, p = 0.03), and septic shock (58.6% vs. 32.2%, p = 0.004). More patients with EBV reactivation required renal replacement therapy (30% vs. 11.9%, p = 0.02). EBV reactivation was also associated with a more inflammatory immune profile. While EBV reactivation was not associated with increased 90-day mortality, it was associated with significantly increased morbidity.

Identifiants

pubmed: 38436725
doi: 10.1007/s00134-024-07345-3
pii: 10.1007/s00134-024-07345-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

418-426

Informations de copyright

© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.

Références

Domart Y, Trouillet J-L, Fagon J-Y et al (1990) Incidence and Morbidity of Cytomegaloviral Infection in Patients with Mediastinitis following Cardiac Surgery. Chest 97:18–22. https://doi.org/10.1378/chest.97.1.18
doi: 10.1378/chest.97.1.18 pubmed: 2153065
Ong G, m., Lowry K, Mahajan S, et al (2004) Herpes simplex type 1 shedding is associated with reduced hospital survival in patients receiving assisted ventilation in a tertiary referral intensive care unit. J Med Virol 72:121–125. https://doi.org/10.1002/jmv.10524
doi: 10.1002/jmv.10524 pubmed: 14635019
Limaye AP, Boeckh M (2010) CMV in critically ill patients: pathogen or bystander? Rev Med Virol 20:372–379. https://doi.org/10.1002/rmv.664
doi: 10.1002/rmv.664 pubmed: 20931610 pmcid: 2987685
Cohen JI (2009) CMV in the ICU: Pathogen or passenger? Crit Care Med 37:2095–2096. https://doi.org/10.1097/CCM.0b013e3181a5e725
doi: 10.1097/CCM.0b013e3181a5e725 pubmed: 19448451 pmcid: 2775818
Luyt C-E, Combes A, Deback C et al (2007) Herpes Simplex Virus Lung Infection in Patients Undergoing Prolonged Mechanical Ventilation. Am J Respir Crit Care Med 175:935–942. https://doi.org/10.1164/rccm.200609-1322°C2OC
doi: 10.1164/rccm.200609-1322°C2OC pubmed: 17234903
Chiche L, Forel JM, Papazian L (2011) The role of viruses in nosocomial pneumonia. Curr Opin Infect 24:152–156. https://doi.org/10.1097/QCO.0b013e328343b6e4
doi: 10.1097/QCO.0b013e328343b6e4
Gkrania-Klotsas E, Langenberg C et al (2012) Higher immunoglobulin G antibody levels against cytomegalovirus are associated with incident ischemic heart disease in the population-based EPIC-Norfolk cohort. J Infect Dis. 206:1897–1903. https://doi.org/10.1093/infdis/jis620
doi: 10.1093/infdis/jis620 pubmed: 23045624
Libert N, Bigaillon C, Chargari C et al (2015) Epstein-Barr Virus Replication in Critically Ill Immunocompetent Patients. Biomed J 38:70–76. https://doi.org/10.4103/2319-4170.132905
doi: 10.4103/2319-4170.132905 pubmed: 25179711
Schober P, Vetter TR (2018) Repeated Measures Designs and Analysis of Longitudinal Data: If at First You Do Not Succeed—Try, Try Again. Anesth Analg 127:569–575. https://doi.org/10.1213/ANE.0000000000003511
doi: 10.1213/ANE.0000000000003511 pubmed: 29905618 pmcid: 6072386
Coşkun O, Yazici E, Şahiner F et al (2017) Cytomegalovirus and Epstein-Barr virus replication in the intensive care unit. Med Klin-Intensivmed Notfallmedizin 112:239–245. https://doi.org/10.1007/s00063-016-016-0198-0c
doi: 10.1007/s00063-016-016-0198-0c
Goh C, Burnham KL, Ansari MA et al (2020) Epstein-Barr virus replication in sepsis due to community acquired pneumonia is associated with increased morbidity and an immunosuppressed host transcriptomic endotype. Sci Rep 10:9838. https://doi.org/10.1038/s41598-020-66713-3
doi: 10.1038/s41598-020-66713-3 pubmed: 32555213 pmcid: 7299986
Smith CA, Conroy LT, Pollock M et al (2010) Detection of herpes viruses in respiratory secretions of patients undergoing artificial ventilation. J Med Virol 82:1406–1409. https://doi.org/10.1002/jmv.21794
doi: 10.1002/jmv.21794 pubmed: 20572072
Ong DSY, Bonten MJM, Spitoni C et al (2017) Epidemiology of Multiple Herpes Viremia in Previously Immunocompetent Patients With Septic Shock. Clin Infect Dis 64:1204–1210. https://doi.org/10.1093/cid/cix120
doi: 10.1093/cid/cix120 pubmed: 28158551
Friedrichs I, Bingold T, Keppler OT et al (2013) Detection of herpesvirus EBV DNA in the lower respiratory tract of ICU patients: a marker of infection of the lower respiratory tract? Med Microbiol Immunol (Berl) 202:431–436. https://doi.org/10.1007/s00430-013-0306-1
doi: 10.1007/s00430-013-0306-1 pubmed: 23900401
Simonnet A, Engelmann I, Moreau A-S et al (2021) High incidence of Epstein-Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19. Infect Dis Now 51:296–299. https://doi.org/10.1016/j.idnow.2021.01.005
doi: 10.1016/j.idnow.2021.01.005 pubmed: 33495765 pmcid: 7816954
Lehner GF, Klein SJ, Zoller H et al (2020) Correlation of interleukin-6 with Epstein-Barr virus levels in COVID-19. Crit Care 24:657. https://doi.org/10.1186/s13054-020-03384-6
doi: 10.1186/s13054-020-03384-6 pubmed: 33228750 pmcid: 7682685
He H, Wang Y, Wu M, Sun B (2017) Positive Epstein-Barr virus detection and mortality in respiratory failure patients admitted to the intensive care unit. Clin Respir J 11:895–900. https://doi.org/10.1111/crj.12433
doi: 10.1111/crj.12433 pubmed: 26663042
Walton AH, Muenzer JT, Rasche D et al (2014) Replication of Multiple Viruses in Patients with Sepsis. PLoS One 9:e98819
doi: 10.1371/journal.pone.0098819 pubmed: 24919177 pmcid: 4053360
Gaudreault E, Fiola S, Olivier M, Gosselin J (2007) Epstein-Barr Virus Induces MCP-1 Secretion by Human Monocytes via TLR2. J Virol 81:8016–8024. https://doi.org/10.1128/JVI.00403-07
doi: 10.1128/JVI.00403-07 pubmed: 17522215 pmcid: 1951286
Samanta M, Iwakiri D, Takada K (2008) Epstein-Barr virus-encoded small RNA induces IL-10 through RIG-I-mediated IRF-3 signaling. Oncogene 27:4150–4160. https://doi.org/10.1038/onc.2008.75
doi: 10.1038/onc.2008.75 pubmed: 18362887
Lay JD, Tsao CJ, Chen JY et al (1997) Upregulation of tumor necrosis factor-alpha gene by Epstein-Barr virus and activation of macrophages in Epstein-Barr virus-infected T cells in the pathogenesis of hemophagocytic syndrome. J Clin Invest 100:1969–1979
doi: 10.1172/JCI119728 pubmed: 9329960 pmcid: 508386
Huang D, Song S-J, Wu Z-Z et al (2017) Epstein-Barr Virus-Induced VEGF and GM-CSF Drive Nasopharyngeal Carcinoma Metastasis via Recruitment and Activation of Macrophages. Cancer Res 77:3591–3604. https://doi.org/10.1158/0008-5472.CAN-16-2706
doi: 10.1158/0008-5472.CAN-16-2706 pubmed: 28484077
Peluso MJ, Deveau T-M, Munter SE et al (2022) Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID. MedRxiv Prepr Serv Health Sci. https://doi.org/10.1101/2022.06.21.22276660
doi: 10.1101/2022.06.21.22276660

Auteurs

François Guiouillier (F)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Percy, Clamart, France.

Jean Derely (J)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Percy, Clamart, France.

Alexandre Salvadori (A)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Bégin, Saint Mandé, France.

Jonas Pochard (J)

Service d'Anesthésie-réanimation Chirurgicale, Hôpital de Bicêtre, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France.

Jérôme Le Goff (J)

Département des Agents Infectieux, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.

Thibault Martinez (T)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Percy, Clamart, France.

Florent Raffin (F)

Institut de Recherche Biomédicale des Armées, Unité d'Analyses Biologiques, Brétigny sur Orge, France.

Philippe Laitselart (P)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Percy, Clamart, France.

Charlotte Beaucreux (C)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Bégin, Saint Mandé, France.

Sonia Priou (S)

CentraleSupelec, Université Paris Saclay, Laboratoire Génie Industriel, Gif-Sur-Yvette, France.

Pierre-Louis Conan (PL)

Service de maladie infectieuse, Hôpital d'Instruction des Armées Bégin, Saint Mandé, France.

Vincent Foissaud (V)

Service de biologie médicale, Hôpital d'Instruction des Armées Percy, Clamart, France.

Aurélie Servonnet (A)

Institut de Recherche Biomédicale des Armées, Unité d'Analyses Biologiques, Brétigny sur Orge, France.

Philippe Vest (P)

Service de biologie médicale, Hôpital d'Instruction des Armées Percy, Clamart, France.

Mathieu Boutonnet (M)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Percy, Clamart, France.

Stéphane de Rudnicki (S)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Percy, Clamart, France.

Christine Bigaillon (C)

Service de biologie médicale, Hôpital d'Instruction des Armées Bégin, Saint Mandé, France.

Nicolas Libert (N)

Service d'Anesthésie-Réanimation, Hôpital d'Instruction des Armées Percy, Clamart, France. dr.libert.nicolas@gmail.com.

Classifications MeSH