jofinЖурнал инфектологииJournal Infectology2072-6732IPO “АIDSSPbR"10.22625/2072-6732-2022-14-4-61-68jofin-1380Research ArticleОригинальное исследованиеOriginal ResearchАспекты реактивации цитомегаловируса у пациентов, находящихся в критическом состоянииAspects of cytomegalovirus reactivation in critically ill patientsГорбачёвВ. В.GorbachevV. V.

Горбачёв Виктор Владимирович – ассистент кафедры инфекционных болезней; тел.: +375-336-96-19-81

Витебск

Vitebsk

gorvik_1994@mail.ruДмитраченкоТ. И.DmitrachenkoT. I.

Дмитраченко Татьяна Ивановна – профессор кафедры инфекционных болезней, д.м.н., профессор; тел.: +375-296-81-61-06

Витебск

Vitebsk

tid74@rambler.ruСемёновВ. М.SemenovV. M.

Семёнов Валерий Михайлович – заведующий кафедрой инфекционных болезней, д.м.н., профессор; тел.: +375-333-46-05-20

Витебск

Vitebsk

vmsemenov@mail.ruЕгоровС. К.EgorovS. K.

Егоров Сергей Константинович – доцент кафедры инфекционных болезней, к.м.н., доцент; тел.: +375-336-75-49-06

Витебск

Vitebsk

delta505@yandex.ruВитебский государственный медицинский университетБеларусьVitebsk State Medical UniversityBelarus2022181020221446168Copyright © Горбачёв В.В., Дмитраченко Т.И., Семёнов В.М., Егоров С.К., 20222022Горбачёв В.В., Дмитраченко Т.И., Семёнов В.М., Егоров С.К.Gorbachev V.V., Dmitrachenko T.I., Semenov V.M., Egorov S.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.niidi.ru/jofin/article/view/1380

Цитомегаловирус играет существенную роль в патологии человека. Первичное инфицирование обычно происходит в детском возрасте, и в последующем формируется пожизненная латенция, при которой вирус реплицируется вследствие ускользания от иммунного ответа. Состояние физиологической или патологической иммуносупрессии может способствовать реактивации цитомегаловируса. В последние годы все больше исследователей приходят к выводу, что у пациентов в критическом состоянии может происходить реактивация цитомегаловируса. Несмотря на имеющиеся сведения, данные о реактивации в этой группе пациентов ограничены относительно небольшими размерами выборки, разнообразием исследуемых групп пациентов, различиями в методологии исследований и вариабельностью в сообщенных результатах, что исключает возможность обобщения результатов.

Цель

Цель: определение частоты и сроков реактивации ЦМВИ у пациентов, находящихся в критическом состоянии, и выявление ее основных клинических особенностей.

Материалы и методы

Материалы и методы: в исследование были включены 118 пациентов в критическом состоянии с тяжелыми бактериальными и вирусно-бактериальными инфекциями, сопровождающимися полиорганной дисфункцией. Реактивация цитомегаловируса определялась обнаружением ДНК вместе с наличием IgG.

Результаты

Результаты. Реактивация была обнаружена в 36,4% случаев. Выявлены частота и сроки реактивации в крови и мокроте, а также тенденции изменения вирусной нагрузки в динамике. Отмечены основные клинические особенности реактивации при различных патологиях (сепсис бактериальной этиологии, COVID-19, несептические критические пациенты). ДНК ЦМВ чаще обнаруживалась в крови пациентов с сепсисом (44,8%) по сравнению с пациентами с COVID-19 (13,0%, p=0,015) и несептическими критическими пациентами (19,2%, p<0,05). При COVID-19 было характерно не только более редкое обнаружение ДНК ЦМВ в крови, но и наименьшие вирусные нагрузки (p<0,05). ДНК ЦМВ в мокроте обнаруживается одинаково часто при сепсисе (38,1%) и COVID-19 (33,3%), однако наиболее высокие вирусные нагрузки характерны для пациентов с сепсисом (p<0,05).

Cytomegalovirus plays an essential role in human pathology. Primary infection usually occurs in childhood and subsequently, a lifelong latency is formed which the virus replicates by evading the immune response. In recent years, more and more researchers have concluded that cytomegalovirus reactivation may occur in critically ill patients. Despite the available evidence, data on reactivation in this group of patients are limited by the relatively small sample size, the variety of patient groups studied, the differences in study methodology, and the variability in reported results, which excludes the possibility of summarizing the results.

This study aimed to determine the frequency of reactivation of cytomegalovirus infection in critically ill patients and to identify its main clinical features.

Materials and methods

Materials and methods. The study included 118 critically ill patients with severe bacterial and viral-bacterial infections accompanied by multiple organ dysfunction. Cytomegalovirus reactivation was determined by the detection of DNA in combination with the presence of IgG.

Results

Results. Reactivation was detected in 36.4% of cases. Frequency and terms of reactivation in blood and sputum as well as trends of viral load changes in dynamics were shown. The main clinical features of reactivation in different pathologies (sepsis of bacterial etiology, COVID-19, non-septic critical patients) were noted. HCMV DNA was more frequently detected in the blood of septic patients (44.8%) compared with COVID-19 (13.0%, p<0.05) and non-septic critically ill patients (19.2%, p<0.05). COVID-19 was characterized not only by lower detection of HCMV DNA in the blood but also by the lowest viral loads (p<0.05). HCMV DNA in sputum was detected comparably frequently in sepsis (38.1%) and COVID-19 (33.3%), but the highest viral loads were characteristic of patients with sepsis (p<0.05).

цитомегаловирусреактивацияCOVID-19сепсисиммуносупрессияcytomegalovirusreactivation infectionCOVID-19sepsisimmunosuppressionReferencesWalton, A.H. et al. Reactivation of multiple viruses in patients with sepsis / A.H. Walton et al. // PloS One. – 2014. Vol. 9, № 2. – P. 98819.Walton, A.H. et al. Reactivation of multiple viruses in patients with sepsis / A.H. Walton et al. // PloS One. – 2014. Vol. 9, № 2. – P. 98819.Sinclair, J. Human cytomegalovirus: Latency and reactivation in the myeloid lineage / J. Sinclair // Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology. – 2008. – Vol. 41, № 3. – P. 180–185.Sinclair, J. Human cytomegalovirus: Latency and reactivation in the myeloid lineage / J. Sinclair // Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology. – 2008. – Vol. 41, № 3. – P. 180–185.Britt, W. Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease / W. Britt // Current Topics in Microbiology and Immunology. 2008. – Vol. 325, – P. 417–470.Britt, W. Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease / W. Britt // Current Topics in Microbiology and Immunology. 2008. – Vol. 325, – P. 417–470.Ong, D.S.Y. et al. Epidemiology of Multiple Herpes Viremia in Previously Immunocompetent Patients With Septic Shock / D.S.Y. Ong et al. // Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. – 2017. – Vol. 64, № 9. – P. 1204–1210.Ong, D.S.Y. et al. Epidemiology of Multiple Herpes Viremia in Previously Immunocompetent Patients With Septic Shock / D.S.Y. Ong et al. // Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. – 2017. – Vol. 64, № 9. – P. 1204–1210.Staras, S.A.S. et al. Seroprevalence of cytomegalovirus infection in the United States, 1988-1994 / S.A.S. Staras et al. // Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. – 2006. – Vol. 43, № 9. – P. 1143–1151.Staras, S.A.S. et al. Seroprevalence of cytomegalovirus infection in the United States, 1988-1994 / S.A.S. Staras et al. // Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. – 2006. – Vol. 43, № 9. – P. 1143–1151.Zuhair, M. et al. Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis / M. Zuhair et al. // Reviews in Medical Virology. – 2019. – Vol. 29, № 3. – P. 2034.Zuhair, M. et al. Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis / M. Zuhair et al. // Reviews in Medical Virology. – 2019. – Vol. 29, № 3. – P. 2034.Dubonosova, E.Yu. et al. Cytomegalovirus Infection in Adolescents of Russian Federation: Results of Cross-Sectional Population Analysis of Seroprevalence / E.Yu. Dubonosova et al. // Pediatric pharmacology. – 2021. – Vol. 18, № 6. – P. 451–459.Dubonosova, E.Yu. et al. Cytomegalovirus Infection in Adolescents of Russian Federation: Results of Cross-Sectional Population Analysis of Seroprevalence / E.Yu. Dubonosova et al. // Pediatric pharmacology. – 2021. – Vol. 18, № 6. – P. 451–459.Ong, D.S.Y. et al. Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome / D.S.Y. Ong et al. // Intensive Care Medicine. – 2016. – Vol. 42, № 3. – P. 333–341.Ong, D.S.Y. et al. Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome / D.S.Y. Ong et al. // Intensive Care Medicine. – 2016. – Vol. 42, № 3. – P. 333–341.Lachance, P. et al. Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis / P. Lachance et al. // Open Forum Infectious Diseases. – 2017. – Vol. 4, № 2. – P. Ofx029.Lachance, P. et al. Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis / P. Lachance et al. // Open Forum Infectious Diseases. – 2017. – Vol. 4, № 2. – P. Ofx029.Osawa, R. & Singh, N. Cytomegalovirus infection in critically ill patients: a systematic review / R. Osawa, N. Singh // Critical Care (London, England). – 2009. – Vol. 13, № 3. – P. 68.Osawa, R. & Singh, N. Cytomegalovirus infection in critically ill patients: a systematic review / R. Osawa, N. Singh // Critical Care (London, England). – 2009. – Vol. 13, № 3. – P. 68.von Müller, L. et al. Active cytomegalovirus infection in patients with septic shock / L. von Müller et al. // Emerging Infectious Diseases. – 2006. – Vol. 12, № 10. – P. 1517–1522.von Müller, L. et al. Active cytomegalovirus infection in patients with septic shock / L. von Müller et al. // Emerging Infectious Diseases. – 2006. – Vol. 12, № 10. – P. 1517–1522.Al-Omari, A. et al. Cytomegalovirus infection in immunocompetent critically ill adults: literature review / A. Al-Omari et al. // Annals of Intensive Care. – 2016. – Vol. 6, № 1. – P. 110.Al-Omari, A. et al. Cytomegalovirus infection in immunocompetent critically ill adults: literature review / A. Al-Omari et al. // Annals of Intensive Care. – 2016. – Vol. 6, № 1. – P. 110.Frantzeskaki, F.G. et al. Cytomegalovirus reactivation in a general, nonimmunosuppressed intensive care unit population: incidence, risk factors, associations with organ dysfunction, and inflammatory biomarkers / F.G. Frantzeskaki et al. // Journal of Critical Care. – 2015. – Vol. 30, № 2. – P. 276–281.Frantzeskaki, F.G. et al. Cytomegalovirus reactivation in a general, nonimmunosuppressed intensive care unit population: incidence, risk factors, associations with organ dysfunction, and inflammatory biomarkers / F.G. Frantzeskaki et al. // Journal of Critical Care. – 2015. – Vol. 30, № 2. – P. 276–281.Papazian, L. et al. Cytomegalovirus reactivation in ICU patients / L. Papazian et al. // Intensive Care Medicine. 2016. – Vol. 42, № 1. – P. 28–37.Papazian, L. et al. Cytomegalovirus reactivation in ICU patients / L. Papazian et al. // Intensive Care Medicine. 2016. – Vol. 42, № 1. – P. 28–37.Chiche, L. et al. Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients / L. Chiche et al. // Critical Care Medicine. – 2009. Vol. 37, № 6. – P. 1850–1857.Chiche, L. et al. Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients / L. Chiche et al. // Critical Care Medicine. – 2009. Vol. 37, № 6. – P. 1850–1857.Davenport, E.E. et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study / E.E. Davenport et al. // The Lancet. Respiratory Medicine. – 2016. – Vol. 4, № 4. – P. 259–271.Davenport, E.E. et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study / E.E. Davenport et al. // The Lancet. Respiratory Medicine. – 2016. – Vol. 4, № 4. – P. 259–271.Binkowska, A.M. Michalak, G. & Słotwiński, R. Current views on the mechanisms of immune responses to trauma and infection / A.M. Binkowska, G. Michalak, R. Słotwiński // Central-European Journal of Immunology. – 2015. – Vol. 40, № 2. – P. 206–216.Binkowska, A.M. Michalak, G. & Słotwiński, R. Current views on the mechanisms of immune responses to trauma and infection / A.M. Binkowska, G. Michalak, R. Słotwiński // Central-European Journal of Immunology. – 2015. – Vol. 40, № 2. – P. 206–216.Reinhart, K. et al. New approaches to sepsis: molecular diagnostics and biomarkers / K. Reinhart et al. // Clinical Microbiology Reviews. – 2012. – Vol. 25, № 4. – P. 609–634.Reinhart, K. et al. New approaches to sepsis: molecular diagnostics and biomarkers / K. Reinhart et al. // Clinical Microbiology Reviews. – 2012. – Vol. 25, № 4. – P. 609–634.

The authors declare that there are no conflicts of interest present.