jofinЖурнал инфектологииJournal Infectology2072-6732IPO “АIDSSPbR"10.22625/2072-6732-2021-13-4-14-24jofin-1265Research ArticleОбзорыReviewИнвазивный аспергиллёз при тяжёлых респираторных вирусных инфекциях (гриппе и COVID-19)Invasive aspergillosis a complication severe respiratory viral infections (influenza and COVID-19)КлимкоН. Н.KlimkoN. N.

заведующий кафедрой клинической микологии, аллергологии и иммунологии, д.м.н., профессор,

Санкт-Петербург

Saint-Petersburg

n_klimko@mail.ruШадривоваО. В.ShadrivovaO. V.

доцент кафедры клинической микологии, аллергологии и иммунологии, к.м.н.,

Санкт-Петербург

Saint-Petersburg

olshadr@mail.ruСеверо-Западный государственный медицинский университет им. И.И. МечниковаРоссияNorth-Western State Medical University named after I.I. MechnikovRussian Federation2021261220211341424Copyright © Климко Н.Н., Шадривова О.В., 20212021Климко Н.Н., Шадривова О.В.Klimko N.N., Shadrivova O.V.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/1265

Инвазивный аспергиллез – жизнеугрожающее осложнение у больных тяжелым гриппом и COVID-19 в отделениях реанимации и интенсивной терапии. Факторы риска развития инвазивного аспергиллеза – транзиторная иммуносупрессия, связанная с тяжелым гриппом и COVID-19, а также применение глюкокортикостероидов и иммуносупрессивных препаратов. При наличии факторов риска, предполагаемых клинических и радиологических признаков инвазивного аспергиллеза необходимо выполнение бронхоскопии и исследование материала, полученного из нижних отделов респираторного тракта: тест на галактоманнан, микроскопия с окраской калькофлюром белым и посев на среду Сабуро. Препаратами выбора для лечения инвазивного аспергиллеза у больных тяжелым гриппом и COVID-19 являются вориконазол или изавуконазол. Альтернативные препараты – липосомальный амфотерицин В, липидный комплекс амфотерицина В и каспофунгин. Возможно проведение комбинированной терапии. Для успешной терапии необходим контроль основного заболевания и устранение или снижение выраженности факторов риска. 

Invasive aspergillosis is a life-threatening complication in patients with severe influenza and COVID-19 in intensive care units. Risk factors for the invasive aspergillosis development are transitory immunosuppression associated with severe influenza and COVID-19, as well as the use of glucocorticosteroids and immunosuppressive therapy. In the presence of risk factors, suspected clinical and radiological signs of invasive aspergillosis, bronchoscopy and examination of material from the lower respiratory tract are necessary: test for galactomannan, microscopy with white calcofluor staining and inoculation on Sabouraud agar medium. Voriconazole or are recommended as first-line treatment for invasive aspergillosis in patients with severe influenza and COVID-19. Amphotericin B Liposomal, Amphotericin B Lipid Complex, and Caspofungin are the alternative options for the invasive aspergillosis treatment. Combination therapy is possible. It is necessary to control the underlying disease with eliminate or reduce the severity of risk factors. 

инвазивный аспергиллёзAspergillus spp.COVID-19CAPA (COVID-19-associated pulmonary aspergillosis)invasive aspergillosisAspergillus spp.COVID-19CAPAСтатья подготовлена при финансовой поддержке компании «Пфайзер».ReferencesSchauwvlieghe A.F.A.D. et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study // The Lancet Respiratory Medicine. 2018. Vol. 6, № 10. P. 782–792.Schauwvlieghe A.F.A.D. et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study // The Lancet Respiratory Medicine. 2018. Vol. 6, № 10. P. 782–792.Marr K.A. et al. Aspergillosis Complicating Severe Coronavirus Disease // Emerg. Infect. Dis. 2021. Vol. 27, № 1. P. 18–25.Marr K.A. et al. Aspergillosis Complicating Severe Coronavirus Disease // Emerg. Infect. Dis. 2021. Vol. 27, № 1. P. 18–25.Гусаров, В.Г. Инвазивный аспергиллёз лёгких у больных COVID-19 / В.Г. Гусаров [и др.] // Журнал инфектологии. – 2021. – Т. 13, № 1. – С. 38–49.Gusarov V.G., Zamyatin M.N., Kamyshova D.A. i dr. Invazivnyj aspergillyoz lyogkih u bol’nyh COVID-19. ZHurnal infektologii, 2021, Tom 13, №1, 38-49.Arastehfar A. et al. COVID-19 Associated Pulmonary Aspergillosis (CAPA)–From Immunology to Treatment // JoF. 2020. Vol. 6, № 2. P. 91.Arastehfar A. et al. COVID-19 Associated Pulmonary Aspergillosis (CAPA)–From Immunology to Treatment // JoF. 2020. Vol. 6, № 2. P. 91.Clancy C.J., Nguyen M.H. Coronavirus Disease 2019, Superinfections, and Antimicrobial Development: What Can We Expect? // Clinical Infectious Diseases. 2020. Vol. 71, № 10. P. 2736–2743.Clancy C.J., Nguyen M.H. Coronavirus Disease 2019, Superinfections, and Antimicrobial Development: What Can We Expect? // Clinical Infectious Diseases. 2020. Vol. 71, № 10. P. 2736–2743.Qin C. et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China // Clinical Infectious Diseases. 2020. Vol. 71, № 15. P. 762–768.Qin C. et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China // Clinical Infectious Diseases. 2020. Vol. 71, № 15. P. 762–768.Salmanton-García J. et al. COVID-19–Associated Pulmonary Aspergillosis, March–August 2020 // Emerg. Infect. Dis. 2021. Vol. 27, № 4. P. 1077–1086.Salmanton-García J. et al. COVID-19–Associated Pulmonary Aspergillosis, March–August 2020 // Emerg. Infect. Dis. 2021. Vol. 27, № 4. P. 1077–1086.Mitaka H. et al. Incidence and mortality of COVID‐19‐associated pulmonary aspergillosis: A systematic review and meta-analysis // Mycoses. 2021. Vol. 64, № 9. P. 993–1001.Mitaka H. et al. Incidence and mortality of COVID-19-associated pulmonary aspergillosis: A systematic review and meta-analysis // Mycoses. 2021. Vol. 64, № 9. P. 993–1001.Dellière S. et al. Risk factors associated with COVID19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort // Clinical Microbiology and Infection. 2020. P. S1198743X20307564.Dellière S. et al. Risk factors associated with COVID19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort // Clinical Microbiology and Infection. 2020. P. S1198743X20307564.Rutsaert L. et al. COVID-19-associated invasive pulmonary aspergillosis // Ann. Intensive Care. 2020. Vol. 10, № 1. P. 71.Rutsaert L. et al. COVID-19-associated invasive pulmonary aspergillosis // Ann. Intensive Care. 2020. Vol. 10, № 1. P. 71.Donnelly J.P. et al. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium // Clinical Infectious Diseases. 2020. Vol. 71, № 6. P. 1367–1376.Donnelly J.P. et al. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium // Clinical Infectious Diseases. 2020. Vol. 71, № 6. P. 1367–1376.Koehler P. et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance // The Lancet Infectious Diseases. 2020. P. S1473309920308471.Koehler P. et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance // The Lancet Infectious Diseases. 2020. P. S1473309920308471.Временные методические рекомендации «Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19)». Версия 12 (21.09.2021) с. 64-66.Vremennye metodicheskie rekomendacii “Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19)”. Versiya 12 (21.09.2021) s. 64-66.van de Veerdonk F.L. et al. Influenza-associated Aspergillosis in Critically Ill Patients // Am J Respir Crit Care Med. 2017. Vol. 196, № 4. P. 524–527.van de Veerdonk F.L. et al. Influenza-associated Aspergillosis in Critically Ill Patients // Am J Respir Crit Care Med. 2017. Vol. 196, № 4. P. 524–527.Мелёхина, Ю.Э. Тяжелый грипп как фактор риска развития инвазивного аспергиллёза лёгких (клинический случай) / Ю.Э. Мелёхина [и др.] // Журнал инфектологии. – 2020. – Т. 12, №1. – С. 96–103.Melyohina YU.E., SHadrivova O.V., Frolova E.V., Borzova YU.V., SHagdileeva E.V., Bogomolova T.S., SHurpickaya O.A., Klimko N.N. Tyazhelyj gripp kak faktor riska razvitiya invazivnogo aspergillyoza lyogkih (klinicheskij _sluchaj). ZHurnal infektologii, 2020, Tom 12, №1, s. 96–103.Crum-Cianflone N.F. Invasive Aspergillosis Associated With Severe Influenza Infections // Open Forum Infectious Diseases. 2016. Vol. 3, № 3. P. ofw171.Crum-Cianflone N.F. Invasive Aspergillosis Associated With Severe Influenza Infections // Open Forum Infectious Diseases. 2016. Vol. 3, № 3. P. ofw171.Wauters J. et al. Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study // Intensive Care Med. 2012. Vol. 38, № 11. P. 1761–1768.Wauters J. et al. Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study // Intensive Care Med. 2012. Vol. 38, № 11. P. 1761–1768.Bartoletti M. et al. Epidemiology of Invasive Pulmonary Aspergillosis Among Intubated Patients With COVID-19: A Prospective Study // Clinical Infectious Diseases. 2020. P. ciaa1065.Bartoletti M. et al. Epidemiology of Invasive Pulmonary Aspergillosis Among Intubated Patients With COVID-19: A Prospective Study // Clinical Infectious Diseases. 2020. P. ciaa1065.Verweij P.E. et al. Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis // Intensive Care Med. 2021.Verweij P.E. et al. Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis // Intensive Care Med. 2021.White P.L. et al. A National Strategy to Diagnose Coronavirus Disease 2019–Associated Invasive Fungal Disease in the Intensive Care Unit // Clinical Infectious Diseases. 2020. P. ciaa1298.White P.L. et al. A National Strategy to Diagnose Coronavirus Disease 2019–Associated Invasive Fungal Disease in the Intensive Care Unit // Clinical Infectious Diseases. 2020. P. ciaa1298. 21. Koehler P. et al. COVID-19 associated pulmonary aspergillosis // Mycoses. 2020. Vol. 63, № 6. P. 528–534.Koehler P. et al. COVID‐19 associated pulmonary aspergillosis // Mycoses. 2020. Vol. 63, № 6. P. 528–534.van Arkel A.L.E. et al. COVID-19–associated Pulmonary Aspergillosis // Am J Respir Crit Care Med. 2020. Vol. 202, № 1. P. 132–135.van Arkel A.L.E. et al. COVID-19–associated Pulmonary Aspergillosis // Am J Respir Crit Care Med. 2020. Vol. 202, № 1. P. 132–135.Dimopoulos G. et al. COVID-19-Associated Pulmonary Aspergillosis (CAPA) // Journal of Intensive Medicine. 2021. P. S2667100X2100027X.Dimopoulos G. et al. COVID-19-Associated Pulmonary Aspergillosis (CAPA) // Journal of Intensive Medicine. 2021. P. S2667100X2100027X.Ullmann A.J. et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMIDECMM-ERS guideline // Clinical Microbiology and Infection. 2018. Vol. 24. P. e1–e38.Ullmann A.J. et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMIDECMM-ERS guideline // Clinical Microbiology and Infection. 2018. Vol. 24. P. e1–e38.Diagnostika i lechenie mikozov v otdeleniyah reanimacii i intensivnoj terapii. Rossijskie nacional’nye rekomendacii. Pod red. N.N. Klimko. M., Borges, 2015. – 92 s.Диагностика и лечение микозов в отделениях реанимации и интенсивной терапии. Российские национальные рекомендации / под ред. Н.Н. Климко. – М.: Боргес, 2015. – 92 с.Wang J. Clinical characteristics of invasive pulmonary aspergillosis in patients with COVID-19 in Zhejiang, China: a retrospective case series. 2020. P. 4.Wang J. Clinical characteristics of invasive pulmonary aspergillosis in patients with COVID-19 in Zhejiang, China: a retrospective case series. 2020. P. 4.Verweij P.E. et al. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion // Intensive Care Med. 2020.Verweij P.E. et al. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion // Intensive Care Med. 2020.Tejerina E.E. et al. Invasive aspergillosis in critically ill patients: An autopsy study // Mycoses. 2019. Vol. 62, № 8. P. 673–679.Tejerina E.E. et al. Invasive aspergillosis in critically ill patients: An autopsy study // Mycoses. 2019. Vol. 62, № 8. P. 673–679.Youssef J., Novosad S.A., Winthrop K.L. Infection Risk and Safety of Corticosteroid Use // Rheumatic Disease Clinics of North America. 2016. Vol. 42, № 1. P. 157–176.Youssef J., Novosad S.A., Winthrop K.L. Infection Risk and Safety of Corticosteroid Use // Rheumatic Disease Clinics of North America. 2016. Vol. 42, № 1. P. 157–176.Ezeokoli O.T., Gcilitshana O., Pohl C.H. Risk Factors for Fungal Co-Infections in Critically Ill COVID-19 Patients, with a Focus on Immunosuppressants // JoF. 2021. Vol. 7, № 7. P. 545.Ezeokoli O.T., Gcilitshana O., Pohl C.H. Risk Factors for Fungal Co-Infections in Critically Ill COVID-19 Patients, with a Focus on Immunosuppressants // JoF. 2021. Vol. 7, № 7. P. 545.Haydour Q. et al. Diagnosis of Fungal Infections. A Systematic Review and Meta-Analysis Supporting American Thoracic Society Practice Guideline // Annals ATS. 2019. Vol. 16, № 9. P. 1179–1188.Haydour Q. et al. Diagnosis of Fungal Infections. A Systematic Review and Meta-Analysis Supporting American Thoracic Society Practice Guideline // Annals ATS. 2019. Vol. 16, № 9. P. 1179–1188.Gao C.A. et al. Bronchoscopy on Intubated Patients with COVID-19 Is Associated with Low Infectious Risk to Operators // Annals ATS. 2021. Vol. 18, № 7. P. 1243–1246.Gao C.A. et al. Bronchoscopy on Intubated Patients with COVID-19 Is Associated with Low Infectious Risk to Operators // Annals ATS. 2021. Vol. 18, № 7. P. 1243–1246.Dabas Y., Mohan A., Xess I. Serum galactomannan antigen as a prognostic and diagnostic marker for invasive aspergillosis in heterogeneous medicine ICU patient population // PLoS ONE / ed. Lazzeri C. 2018. Vol. 13, № 4. P. e0196196.Dabas Y., Mohan A., Xess I. Serum galactomannan antigen as a prognostic and diagnostic marker for invasive aspergillosis in heterogeneous medicine ICU patient population // PLoS ONE / ed. Lazzeri C. 2018. Vol. 13, № 4. P. e0196196.De Pauw B. et al. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group // Clin Infect Dis. 2008. Vol. 46, № 12. P. 1813–1821.De Pauw B. et al. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group // Clin Infect Dis. 2008. Vol. 46, № 12. P. 1813–1821.De Pauw B. et al. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group // Clin Infect Dis. 2008. Vol. 46, № 12. P. 1813–1821.

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