nach oben

Erschienen in:

18.05.2022 | COVID-19 | Original

Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality

verfasst von: Ilenia Gatto, Emanuela Biagioni, Irene Coloretti, Carlotta Farinelli, Camilla Avoni, Valeria Caciagli, Stefano Busani, Mario Sarti, Monica Pecorari, William Gennari, Giovanni Guaraldi, Erica Franceschini, Marianna Meschiari, Cristina Mussini, Roberto Tonelli, Enrico Clini, Andrea Cossarizza, Massimo Girardis, the Modena COVID-19 Working Group

Erschienen in: Intensive Care Medicine | Ausgabe 6/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of patients affected by coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU).

Methods

Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models.

Results

CMV blood reactivation was observed in 88 patients (20.4%) of the 431 patients studied. Simplified Acute Physiology Score (SAPS) II score (HR 1031, 95% CI 1010–1053, p = 0.006), platelet count (HR 0.0996, 95% CI 0.993–0.999, p = 0.004), invasive mechanical ventilation (HR 2611, 95% CI 1223–5571, p = 0.013) and secondary bacterial infection (HR 5041; 95% CI 2852–8911, p < 0.0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67.0%) than in patients without (24.5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1141, 95% CI 0.757–1721, p = 0.528).

Conclusion

The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.

Nur mit Berechtigung zugänglich

Limaye AP, Kirby KA, Rubenfeld GD et al (2008) Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 300:413–422. https://doi.org/10.1001/jama.300.4.413CrossRefPubMedPubMedCentral

Imlay H, Dasgupta S, Boeckh M et al (2021) Risk factors for cytomegalovirus reactivation and association with outcomes in critically ill adults with sepsis: a pooled analysis of prospective studies. J Infect Dis 223:2108–2112. https://doi.org/10.1093/infdis/jiaa697CrossRefPubMed

Hraiech S, Bonnardel E, Guervilly C et al (2019) Herpes simplex virus and Cytomegalovirus reactivation among severe ARDS patients under veno-venous ECMO. Ann Intensive Care 9:142. https://doi.org/10.1186/s13613-019-0616-6CrossRefPubMedPubMedCentral

Libert N, Bigaillon C, Chargari C et al (2015) Epstein-Barr virus reactivation in critically ill immunocompetent patients. Biomed J 38:70–76. https://doi.org/10.4103/2319-4170.132905CrossRefPubMed

Imlay H, Limaye AP (2020) Current understanding of cytomegalovirus reactivation in critical illness. J Infect Dis 221:S94–S102. https://doi.org/10.1093/infdis/jiz638CrossRefPubMedPubMedCentral

Le Balc’h P, Pinceaux K, Pronier C et al (2020) Herpes simplex virus and cytomegalovirus reactivations among severe COVID-19 patients. Crit Care 24:530. https://doi.org/10.1186/s13054-020-03252-3CrossRefPubMedPubMedCentral

Moniz P, Brito S, Póvoa P (2021) SARS-CoV-2 and cytomegalovirus co-infections-a case series of critically ill patients. J Clin Med 10:2792. https://doi.org/10.3390/jcm10132792CrossRefPubMedPubMedCentral

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.2021.01.005CrossRefPubMedPubMedCentral

Franceschini E, Cozzi-Lepri A, Santoro A et al (2021) Herpes simplex virus re-activation in patients with SARS-CoV-2 pneumonia: a prospective, observational study. Microorganisms 9:1896. https://doi.org/10.3390/microorganisms9091896CrossRefPubMedPubMedCentral

10.

Meyer A, Buetti N, Houhou-Fidouh N et al (2021) HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients. Crit Care 25:417. https://doi.org/10.1186/s13054-021-03843-8CrossRefPubMedPubMedCentral

11.

Al-Omari A, Aljamaan F, Alhazzani W et al (2016) Cytomegalovirus infection in immunocompetent critically ill adults: literature review. Ann Intensive Care 6:110. https://doi.org/10.1186/s13613-016-0207-8CrossRefPubMedPubMedCentral

12.

Schildermans J, De Vlieger G (2020) Cytomegalovirus: a troll in the ICU? Overview of the literature and perspectives for the future. Front Med (Lausanne) 7:188. https://doi.org/10.3389/fmed.2020.00188CrossRef

13.

Papazian L, Hraiech S, Lehingue S et al (2016) Cytomegalovirus reactivation in ICU patients. Intensive Care Med 42:28–37. https://doi.org/10.1007/s00134-015-4066-9CrossRefPubMed

14.

Chiche L, Forel J-M, Roch A et al (2009) Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med 37:1850–1857. https://doi.org/10.1097/CCM.0b013e31819ffea6CrossRefPubMed

15.

Barry SM, Johnson MA, Janossy G (2000) Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited. Bone Marrow Transpl 26:591–597. https://doi.org/10.1038/sj.bmt.1702562CrossRef

16.

Papazian L, Thomas P, Bregeon F et al (1998) Open-lung biopsy in patients with acute respiratory distress syndrome. Anesthesiology 88:935–944. https://doi.org/10.1097/00000542-199804000-00013CrossRefPubMed

17.

Söderberg-Nauclér C (2021) Does reactivation of cytomegalovirus contribute to severe COVID-19 disease? Immun Ageing 18:12. https://doi.org/10.1186/s12979-021-00218-zCrossRefPubMedPubMedCentral

18.

Papazian L, Jaber S, Hraiech S et al (2021) Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation. Ann Intensive Care 11:33. https://doi.org/10.1186/s13613-020-00793-2CrossRefPubMedPubMedCentral

19.

Cowley NJ, Owen A, Shiels SC et al (2017) Safety and efficacy of antiviral therapy for prevention of cytomegalovirus reactivation in immunocompetent critically ill patients: a randomized clinical trial. JAMA Intern Med 177:774–783. https://doi.org/10.1001/jamainternmed.2017.0895CrossRefPubMedPubMedCentral

20.

Limaye AP, Stapleton RD, Peng L et al (2017) Effect of ganciclovir on IL-6 levels among cytomegalovirus-seropositive adults with critical illness: a randomized clinical trial. JAMA 318:731–740. https://doi.org/10.1001/jama.2017.10569CrossRefPubMedPubMedCentral

21.

Definition Task Force ARDS, Ranieri VM, Rubenfeld GD et al (2012) Acute respiratory distress syndrome: the Berlin Definition. JAMA 307:2526–2533. https://doi.org/10.1001/jama.2012.5669CrossRef

22.

World Health Organization (2021) COVID-19 clinical management: living guidance. World Health Organization, Geneva

23.

Mussini C, Falcone M, Nozza S et al (2021) Therapeutic strategies for severe COVID-19: a position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT). Clin Microbiol Infect 27:389–395. https://doi.org/10.1016/j.cmi.2020.12.011CrossRefPubMedPubMedCentral

24.

Steinberg KP, Hudson LD, Goodman RB et al (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684. https://doi.org/10.1056/NEJMoa051693CrossRefPubMed

25.

Torres A, Niederman MS, Chastre J et al (2017) International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J 50:1700582. https://doi.org/10.1183/13993003.00582-2017CrossRefPubMed

26.

Manian FA (2009) IDSA guidelines for the diagnosis and management of intravascular catheter-related bloodstream infection. Clin Infect Dis 49:1770–1771. https://doi.org/10.1086/648113CrossRefPubMed

27.

Koehler P, Bassetti M, Chakrabarti A et al (2021) Defining and managing COVID-19-associated pulmonary Aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis 21:e149–e162. https://doi.org/10.1016/S1473-3099(20)30847-1CrossRefPubMed

28.

Fryer JF, Heath AB, Anderson R et al (2010) Collaborative study to evaluate the proposed 1st [first] WHO international standard for human cytomegalovirus (HCMV) for nucleic acid amplification (NAT)-based assays. World Health Organization, Geneva

29.

Saade A, Moratelli G, Azoulay E, Darmon M (2021) Herpesvirus reactivation during severe COVID-19 and high rate of immune defect. Infect Dis Now 51:676–679. https://doi.org/10.1016/j.idnow.2021.07.005CrossRefPubMedPubMedCentral

30.

Busani S, Bedini A, Biagioni E et al (2021) Two fatal cases of acute liver failure due to HSV-1 infection in COVID-19 patients following immunomodulatory therapies. Clin Infect Dis 73:e252–e255. https://doi.org/10.1093/cid/ciaa1246CrossRefPubMed

31.

Osuchowski MF, Winkler MS, Skirecki T et al (2021) The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med 9:622–642. https://doi.org/10.1016/S2213-2600(21)00218-6CrossRefPubMedPubMedCentral

32.

Hosseini SF, Behnam-Roudsari S, Alavinia G et al (2021) Diagnostic and prognostic value of Sepsis-Induced coagulopathy and International Society on Thrombosis and Hemostasis scoring systems in COVID-19-associated disseminated intravascular coagulopathy. J Res Med Sci 26:102. https://doi.org/10.4103/jrms.JRMS_1295_20CrossRefPubMedPubMedCentral

33.

Lachance P, Chen J, Featherstone R, Sligl WI (2017) Association between cytomegalovirus reactivation and clinical outcomes in immunocompetent critically ill patients: a systematic review and meta-analysis. Open Forum Infect Dis 4:029. https://doi.org/10.1093/ofid/ofx029CrossRef

34.

Loftus TJ, Ungaro R, Dirain M et al (2021) Overlapping but disparate inflammatory and immunosuppressive responses to SARS-CoV-2 and bacterial sepsis: an immunological time course analysis. Front Immunol 12:792448. https://doi.org/10.3389/fimmu.2021.792448CrossRefPubMedPubMedCentral

35.

Jaber S, Chanques G, Borry J et al (2005) Cytomegalovirus infection in critically ill patients: associated factors and consequences. Chest 127:233–241. https://doi.org/10.1378/chest.127.1.233CrossRefPubMed

36.

Rubio I, Osuchowski MF, Shankar-Hari M et al (2019) Current gaps in sepsis immunology: new opportunities for translational research. Lancet Infect Dis 19:e422–e436. https://doi.org/10.1016/S1473-3099(19)30567-5CrossRefPubMed

37.

Venet F, Davin F, Guignant C et al (2010) Early assessment of leukocyte alterations at diagnosis of septic shock. Shock 34:358–363. https://doi.org/10.1097/SHK.0b013e3181dc0977CrossRefPubMed

38.

Clari MA, Aguilar G, Benet I et al (2013) Evaluation of cytomegalovirus (CMV)-specific T-cell immunity for the assessment of the risk of active CMV infection in non-immunosuppressed surgical and trauma intensive care unit patients. J Med Virol 85:1802–1810. https://doi.org/10.1002/jmv.23621CrossRefPubMed

39.

Kuo C-W, Wang S-Y, Tsai H-P et al (2021) Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients: a retrospective cohort study. J Microbiol Immunol Infect S1684–1182(21):00057–00058. https://doi.org/10.1016/j.jmii.2021.03.005CrossRef

Titel: Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality
verfasst von: Ilenia Gatto
Emanuela Biagioni
Irene Coloretti
Carlotta Farinelli
Camilla Avoni
Valeria Caciagli
Stefano Busani
Mario Sarti
Monica Pecorari
William Gennari
Giovanni Guaraldi
Erica Franceschini
Marianna Meschiari
Cristina Mussini
Roberto Tonelli
Enrico Clini
Andrea Cossarizza
Massimo Girardis
the Modena COVID-19 Working Group
Publikationsdatum: 18.05.2022
Verlag: Springer Berlin Heidelberg
Schlagwort: COVID-19
Erschienen in: Intensive Care Medicine / Ausgabe 6/2022
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-022-06716-y

Neu im Fachgebiet AINS

Blutdrucksenkung schon im Rettungswagen bei akutem Schlaganfall?

31.05.2024 Apoplex Nachrichten

Der optimale Ansatz für die Blutdruckkontrolle bei Patientinnen und Patienten mit akutem Schlaganfall ist noch nicht gefunden. Ob sich eine frühzeitige Therapie der Hypertonie noch während des Transports in die Klinik lohnt, hat jetzt eine Studie aus China untersucht.

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

28.05.2024 Häusliche Gewalt Nachrichten

In der Notaufnahme wird die Chance, Opfer von häuslicher Gewalt zu identifizieren, von Orthopäden und Orthopädinnen offenbar zu wenig genutzt. Darauf deuten die Ergebnisse einer Fragebogenstudie an der Sahlgrenska-Universität in Schweden hin.

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

hier abonnieren

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality

Abstract

Purpose

Methods

Results

Conclusion

Neu im Fachgebiet AINS

Blutdrucksenkung schon im Rettungswagen bei akutem Schlaganfall?

Ähnliche Überlebensraten nach Reanimation während des Transports bzw. vor Ort

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

Update AINS

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2022

The TARGET trial as a plea for model-informed precision dosing of piperacillin/tazobactam in patients with sepsis

Full enteral nutrition should be avoided among patients with high vasopressor dose and low flow state

Correction to: Increased 30-day mortality in very old ICU patients with COVID-19 compared to patients with respiratory failure without COVID-19

Time course of physiological variables during inter-hospital helicopter transport of ventilated COVID-19 patients

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Staying optimistic in the face of war

Neu im Fachgebiet AINS

Blutdrucksenkung schon im Rettungswagen bei akutem Schlaganfall?

Ähnliche Überlebensraten nach Reanimation während des Transports bzw. vor Ort

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

Update AINS