Novikova VP, Polunina AV, Bannova SL, Balashov AL, Dudurich VV, Danilov LG, Blinov AE, Varlamova ON, Seits AV, Kukes EA. The effectiveness of the synbiotic Maxilac® for the new coronavirus infection after antibacterial therapy. Pediatrics. Consilium Medicum. 2024;2:167–172. DOI: 10.26442/26586630.2024.2.202935
Эффективность применения синбиотика Максилак® при новой коронавирусной инфекции после антибактериальной терапии
Новикова В.П., Полунина А.В., Баннова С.Л., Балашов А.Л., Дудурич В.В., Данилов Л.Г., Блинов А.Е., Варламова О.Н., Сейц А.В., Кукес Е.А. Эффективность применения синбиотика Максилак® при новой коронавирусной инфекции после антибактериальной терапии. Педиатрия. Consilium Medicum.
2024;2:167–172. DOI: 10.26442/26586630.2024.2.202935
Novikova VP, Polunina AV, Bannova SL, Balashov AL, Dudurich VV, Danilov LG, Blinov AE, Varlamova ON, Seits AV, Kukes EA. The effectiveness of the synbiotic Maxilac® for the new coronavirus infection after antibacterial therapy. Pediatrics. Consilium Medicum. 2024;2:167–172. DOI: 10.26442/26586630.2024.2.202935
Новая коронавирусная инфекция (COVID-19), возникшая в 2019 г., является инфекцией, вызываемой вирусом SARS-CoV-2. Несмотря на то что SARS-CoV-2 преимущественно поражает дыхательную систему, многочисленные исследования свидетельствуют о значительном вовлечении желудочно-кишечного тракта при COVID-19, особенно у детей. Цель. Оценить влияние приема синбиотика Максилак® у детей при COVID-19 после антибактериальной терапии (АБТ). Материалы и методы. Проведено клиническое пострегистрационное открытое наблюдательное проспективное одноцентровое исследование с минимальной интервенцией. Изучен микробиом детей с COVID-19. Включены 12 детей с COVID-19, осложненной бактериальной инфекцией (пневмонией, синуситом, отитом), получающих АБТ и далее принимающих в течение 4 нед синбиотик Максилак®. Осуществлен сбор данных пациентов: жалобы, анамнез, клинический статус, исследование кишечной микробиоты (КМ) методом 16S секвенирования, кала на зонулин, анализ назначения лекарственных средств. Забор материала осуществляли у больных с COVID-19 в 3 точках: на момент острого заболевания COVID-19, на момент выздоровления от COVID-19, через 4 нед после начала приема синбиотика. Результаты. Назначение синбиотика Максилак® больным, получившим АБТ при бактериальных осложнениях СOVID-19, купирует клиническую гастроэнтерологическую симптоматику, предотвращает развитие дисбиоза и нормализует кишечную проницаемость. Полученные результаты свидетельствуют о значимых изменениях в КМ после АБТ при осложненном течении COVID-19 и нормализующем влиянии синбиотика Максилак® на КМ в процессе приема в течение 30 дней. Назначение синбиотика Максилак® в группе детей с СOVID-19, получавших АБТ, не имело побочных эффектов и являлось безопасным. Заключение. Детям с COVID-19, осложненной бактериальной инфекцией, получавшим АБТ, после выздоровления рекомендуется назначение синбиотика Максилак® курсом не менее 30 дней.
Ключевые слова: вирус SARS-Cov-2, новая коронавирусная инфекция, COVID-19, кишечная проницаемость, кишечный микробиом, 16S секвенирование, зонулин, постковидный период, Максилак
________________________________________________
The new coronavirus infection (COVID-19) that emerged in 2019 is a infection caused by the SARS-CoV-2 virus. Although SARS-CoV-2 predominantly affects the respiratory system, numerous studies suggest significant gastrointestinal involvement in COVID-19, particularly in children. Aim. To evaluate the effect of the synbiotic Maxilac® in children with COVID-19 after antibacterial therapy (ABT). Materials and methods. A clinical post-approval open-label observational prospective single-center study with minimal intervention was conducted. The microbiome of children with COVID-19 was studied. Twelve children with COVID-19 complicated by a bacterial infection (pneumonia, sinusitis, otitis) were included, receiving ABT and then taking the synbiotic Maxilac® for 4 weeks. Patient data were collected: symptoms, medical history, clinical status, study of intestinal microbiota (IM) by 16S sequencing, stool test for zonulin, and review of drug therapy. The material was sampled in patients with COVID-19 at 3 time points: at the time of acute COVID-19 disease, at the time of recovery from COVID-19, and 4 weeks after starting the synbiotic therapy. Results. The administration of the synbiotic Maxilac® to patients who received ABT for bacterial complications of COVID-19 relieves clinical gastroenterological symptoms, prevents the development of dysbiosis, and normalizes intestinal permeability. The results indicated significant changes in IM after ABT in complicated COVID-19 and the normalizing effect of synbiotic Maxilac® on IM during administration for 30 days. The synbiotic Maxilac® in the group of children with COVID-19 who received ABT had no side effects and was safe. Conclusion. Children with COVID-19, complicated by a bacterial infection, treated with ABT are recommended to receive the synbiotic Maxilac® for at least 30 days after recovery.
1. Tregoning JS, Flight KE, Higham SL, et al. Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape. Nat Rev Immunol. 2021;21(10):626-36. DOI:10.1038/s41577-021-00592-1
2. Files JK, Sarkar S, Fram TR, et al. Duration of post-COVID-19 symptoms is associated with sustained SARS-CoV-2-specific immune responses. JCI Insight. 2021;6(15). DOI:10.1172/jci.insight.151544
3. Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020;369(6499):50-4. DOI:10.1126/science.abc1669
4. Zang R, Gomez Castro MF, McCune BT, et al. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci Immunol. 2020;5(47). DOI:10.1126/sciimmunol.abc3582
5. Zuo T, Liu Q, Zhang F, et al. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. 2021;70(2):276-84. DOI:10.1136/gutjnl-2020-322294
6. Xiao F, Sun J, Xu Y, et al. Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19. Emerg Infect Dis. 2020;26(8):1920-2. DOI:10.3201/eid2608.200681
7. Natarajan A, Zlitni S, Brooks EF, et al. Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection. Med. 2022;3(6):371-87.e9. DOI:10.1016/j.medj.2022.04.001
8. Zollner A, Koch R, Jukic A, et al. Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases. Gastroenterology.
2022;163(2):495-506.e8. DOI:10.1053/j.gastro.2022.04.037
9. Cheung KS, Hung IFN, Chan PPY, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. Gastroenterology. 2020;159(1):81-95. DOI:10.1053/j.gastro.2020.03.065
10. Mao R, Qiu Y, He JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(7):667-78. DOI:10.1016/S2468-1253(20)30126-6
11. Song Y, Liu P, Shi XL, et al. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut. 2020;69(6):1143-4. DOI:10.1136/gutjnl-2020-320891
12. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. DOI:10.1001/jama.2020.1585
13. Gilbert JA, Blaser MJ, Caporaso JG, et al. Current understanding of the human microbiome. Nat Med. 2018;24(4):392-400. DOI:10.1038/nm.4517
14. Новикова В.П., Полунина А.В., Баннова С.Л., и др. Состояние желудочно-кишечного тракта у детей при новой коронавирусной инфекции и в постковидный период. Роль синбиотика в коррекции клинических симптомов, кишечной микробиоты и проницаемости кишечной стенки. РМЖ. Мать и дитя. 2023;6(3):283-9 [Novikova VP, Polunina AV, Bannova SL, et al. Gastrointestinal tract in children with novel coronavirus infection and post-COVID-19 syndrome. The role of synbiotics for improving clinical symptoms, gut microbiota, and intestinal permeability. Russian Journal of Woman and Child Health. 2023;6(3):283-9 (in Russian)]. DOI:10.32364/2618-8430-2023-6-3-10
15. Гриневич В.Б., Лазебник Л.Б., Кравчук Ю.А., и др. Поражения органов пищеварения при постковидном синдроме. Клинические рекомендации. Экспериментальная и клиническая гастроэнтерология. 2022;12:4-68 [Grinevich VB, Lazebnik LB, Kravchuk YuA, et al. Gastrointestinal disorders in post-COVID syndrome. Clinical guidelines. Experimental and Clinical Gastroenterology. 2022;12:4-68 (in Russian)]. DOI:10.31146/1682-8658-ecg-208-12-4-68
16. Новикова В.П., Хавкин А.И., Горелов А.В., Полунина А.В. Ось «легкие-кишечник» и COVID-инфекция. Инфекционные болезни. 2021;19(1):91-6 [Novikova VP, Khavkin AI, Gorelov AV, Polunina A.V. The lung-gut axis and COVID-19. Infekc. Bolezni (Infectious Diseases). 2021;19(1):91-6 (in Russian)]. DOI: 10.20953/1729-9225-2021-1-91-96
17. Полунина А.В., Новикова В.П., Блинов А.Е., и др. Динамика уровня зонулина в стуле при инфекции COVID-19 и в постковидный период у детей. Инфекционные болезни. 2022;20(3):35-40 [Polunina AV, Novikova VP, Blinov AE, et al. Dynamics of fecal zonulin levels in COVID-19 and in the post-covid period in children. Infekc. Bolezni (Infectious Diseases). 2022;20(3):35-40 (in Russian)]. DOI:10.20953/1729-9225-2022-3-35-40
18. Xu R, Liu P, Zhang T, et al. Progressive deterioration of the upper respiratory tract and the gut microbiomes in children during the early infection stages of COVID-19. J Genet Genomics. 2021;48(9):803-14. DOI:10.1016/j.jgg.2021.05.004
19. Zolnikova O, Komkova I, Potskherashvili N, et al. Application of probiotics for acute respiratory tract infections. Italian Journal of Medicine.
2018;12(1):32-8. DOI:10.4081/itjm.2018.931
20. Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015;(2):CD006895. DOI:10.1002/14651858.CD006895.pub3
21. Wang Y, Li X, Ge T, et al. Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016;95(31):e4509. DOI:10.1097/MD.0000000000004509
22. Manzanares W, Lemieux M, Langlois PL, Wischmeyer PE. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. Crit Care. 2016;19:262. DOI:10.1186/s13054-016-1434-y
23. Sarkar A, Yoo JY, Valeria Ozorio Dutra S, et al. The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases. J Clin Med. 2021;10(3). DOI:10.3390/jcm10030459
24. Lange K, Buerger M, Stallmach A, Bruns T. Effects of Antibiotics on Gut Microbiota. Dig Dis. 2016;34(3):260-8. DOI:10.1159/000443360
25. Mamieva Z, Poluektova E, Svistushkin V, et al. Antibiotics, gut microbiota, and irritable bowel syndrome: what are the relations? World J Gastroenterol. 2022;28(12):1204-19. DOI:10.3748/wjg.v28.i12.1204
26. Горелов А.В., Усенко Д.В., Мелехина Е.В., и др. Влияние пробиотика Saccharomyces boulardii CNCM I-745 на развитие антибиотикассоциированного синдрома у детей, получающих системную антибактериальную терапию по поводу инфекций нижних дыхательных путей. Вопросы практической педиатрии. 2024;22(2):15-22 [Gorelov AV, Usenko DV, Melekhina EV, et al. The effect of the Saccharomyces boulardii CNCM I-745 probiotic on the development of antibiotic-associated syndrome in children receiving systemic antibacterial therapy for lower respiratory tract infections. Clinical Practice in Pediatrics. 2024;22(2):15-22 (in Russian)]. DOI:10.20953/1817-7646-2024-2-15-22
________________________________________________
1. Tregoning JS, Flight KE, Higham SL, et al. Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape. Nat Rev Immunol. 2021;21(10):626-36. DOI:10.1038/s41577-021-00592-1
2. Files JK, Sarkar S, Fram TR, et al. Duration of post-COVID-19 symptoms is associated with sustained SARS-CoV-2-specific immune responses. JCI Insight. 2021;6(15). DOI:10.1172/jci.insight.151544
3. Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020;369(6499):50-4. DOI:10.1126/science.abc1669
4. Zang R, Gomez Castro MF, McCune BT, et al. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci Immunol. 2020;5(47). DOI:10.1126/sciimmunol.abc3582
5. Zuo T, Liu Q, Zhang F, et al. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. 2021;70(2):276-84. DOI:10.1136/gutjnl-2020-322294
6. Xiao F, Sun J, Xu Y, et al. Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19. Emerg Infect Dis. 2020;26(8):1920-2. DOI:10.3201/eid2608.200681
7. Natarajan A, Zlitni S, Brooks EF, et al. Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection. Med. 2022;3(6):371-87.e9. DOI:10.1016/j.medj.2022.04.001
8. Zollner A, Koch R, Jukic A, et al. Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases. Gastroenterology.
2022;163(2):495-506.e8. DOI:10.1053/j.gastro.2022.04.037
9. Cheung KS, Hung IFN, Chan PPY, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. Gastroenterology. 2020;159(1):81-95. DOI:10.1053/j.gastro.2020.03.065
10. Mao R, Qiu Y, He JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020;5(7):667-78. DOI:10.1016/S2468-1253(20)30126-6
11. Song Y, Liu P, Shi XL, et al. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut. 2020;69(6):1143-4. DOI:10.1136/gutjnl-2020-320891
12. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. DOI:10.1001/jama.2020.1585
13. Gilbert JA, Blaser MJ, Caporaso JG, et al. Current understanding of the human microbiome. Nat Med. 2018;24(4):392-400. DOI:10.1038/nm.4517
14. Novikova VP, Polunina AV, Bannova SL, et al. Gastrointestinal tract in children with novel coronavirus infection and post-COVID-19 syndrome. The role of synbiotics for improving clinical symptoms, gut microbiota, and intestinal permeability. Russian Journal of Woman and Child Health. 2023;6(3):283-9 (in Russian). DOI:10.32364/2618-8430-2023-6-3-10
15. Grinevich VB, Lazebnik LB, Kravchuk YuA, et al. Gastrointestinal disorders in post-COVID syndrome. Clinical guidelines. Experimental and Clinical Gastroenterology. 2022;12:4-68 (in Russian). DOI:10.31146/1682-8658-ecg-208-12-4-68
16. Novikova VP, Khavkin AI, Gorelov AV, Polunina A.V. The lung-gut axis and COVID-19. Infekc. Bolezni (Infectious Diseases). 2021;19(1):91-6 (in Russian).
DOI: 10.20953/1729-9225-2021-1-91-96
17. Polunina AV, Novikova VP, Blinov AE, et al. Dynamics of fecal zonulin levels in COVID-19 and in the post-covid period in children. Infekc. Bolezni (Infectious Diseases).
2022;20(3):35-40 (in Russian). DOI:10.20953/1729-9225-2022-3-35-40
18. Xu R, Liu P, Zhang T, et al. Progressive deterioration of the upper respiratory tract and the gut microbiomes in children during the early infection stages of COVID-19. J Genet Genomics. 2021;48(9):803-14. DOI:10.1016/j.jgg.2021.05.004
19. Zolnikova O, Komkova I, Potskherashvili N, et al. Application of probiotics for acute respiratory tract infections. Italian Journal of Medicine.
2018;12(1):32-8. DOI:10.4081/itjm.2018.931
20. Hao Q, Dong BR, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2015;(2):CD006895. DOI:10.1002/14651858.CD006895.pub3
21. Wang Y, Li X, Ge T, et al. Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2016;95(31):e4509. DOI:10.1097/MD.0000000000004509
22. Manzanares W, Lemieux M, Langlois PL, Wischmeyer PE. Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis. Crit Care. 2016;19:262. DOI:10.1186/s13054-016-1434-y
23. Sarkar A, Yoo JY, Valeria Ozorio Dutra S, et al. The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases. J Clin Med. 2021;10(3). DOI:10.3390/jcm10030459
24. Lange K, Buerger M, Stallmach A, Bruns T. Effects of Antibiotics on Gut Microbiota. Dig Dis. 2016;34(3):260-8. DOI:10.1159/000443360
25. Mamieva Z, Poluektova E, Svistushkin V, et al. Antibiotics, gut microbiota, and irritable bowel syndrome: what are the relations? World J Gastroenterol. 2022;28(12):1204-19. DOI:10.3748/wjg.v28.i12.1204
26. Gorelov AV, Usenko DV, Melekhina EV, et al. The effect of the Saccharomyces boulardii CNCM I-745 probiotic on the development of antibiotic-associated syndrome in children receiving systemic antibacterial therapy for lower respiratory tract infections. Clinical Practice in Pediatrics. 2024;22(2):15-22 (in Russian). DOI:10.20953/1817-7646-2024-2-15-22
1ФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России, Санкт-Петербург, Россия; 2СПб ГБУЗ «Городская поликлиника №56», Санкт-Петербург, Россия; 3ООО «СЕРБАЛАБ», Санкт-Петербург, Россия; 4ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*novikova-vp@mail.ru
________________________________________________
Valeriya P. Novikova*1, Anna V. Polunina1, Svetlana L. Bannova1, Aleksey L. Balashov1,2, Vasilisa V. Dudurich3, Lavrentii G. Danilov3, Alexander E. Blinov1, Olga N. Varlamova1, Antonina V. Seits1, Evgeniia A. Kukes4
1Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia; 2City Polyclinic №56, Saint Petersburg, Russia; 3CerbaLab Ltd, Saint Petersburg, Russia; 4Pirogov Russian National Research Medical University, Moscow, Russia
*novikova-vp@mail.ru