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Особенности течения COVID-19 у больных сахарным диабетом 2-го типа
Особенности течения COVID-19 у больных сахарным диабетом 2-го типа
Карасева Е.А., Мартынов В.А., Филатова Т.Е., Малеев В.В., Гришин В.Ю., Пронин Н.С., Вербицкая Е.И., Попова В.И. Особенности течения COVID-19 у больных сахарным диабетом 2-го типа. Терапевтический архив. 2023;95(11):913–918. DOI: 10.26442/00403660.2023.11.202478
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
________________________________________________
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Аннотация
Цель. Выявить особенности течения COVID-19 у пациентов с сахарным диабетом 2-го типа (СД 2) в зависимости от приема гипогликемической терапии на догоспитальном этапе во взаимосвязи с функциональным состоянием почек.
Материалы и методы. Проведен ретроспективный анализ 291 истории болезни пациентов с COVID-19 и СД 2, госпитализированных в ГБУ РО «ОКБ им. Н.А. Семашко» с января по декабрь 2021 г., с включением основных клинико-лабораторных параметров.
Результаты. Среди госпитализированных больных COVID-19 пациенты с СД 2 имели более высокую летальность. Анализ историй болезни умерших пациентов с COVID-19 и СД 2 показал, что при поступлении показатели индекса массы тела (ИМТ), С-реактивного белка, креатинина были выше, чем у выживших, и составили соответственно: по ИМТ – 33 [30; 39] и 33 [28; 36] кг/м3; p=0,039, по уровню С-реактивного белка – 77 [47,5; 106,0] и 57 [27,0; 89,0] мг/л; p=0,015, по уровню креатинина – 89 [70,0; 144,0] и 82 [66,0; 101,0] мкмоль/л; р=0,039. Установлено, что на 2-й неделе госпитализации в группе умерших пациентов с COVID-19 и СД 2 уровень креатинина был статистически значимо выше, чем у выживших больных, и составил соответственно 94,5 [71,5; 141,0] и 72,5 [57,0; 88,0] мкмоль/л; p<0,001. Вероятность летального исхода у госпитализированных пациентов с COVID-19 и СД 2 зависела от ИМТ и уровня креатинина на 2-й неделе госпитализации. Пациенты с СД 2, которые на догоспитальном этапе принимали ингибиторы дипептидилпептидазы-4/агонисты рецепторов глюкагоноподобного пептида-1/ингибиторы натрий-глюкозного котранспортера 2-го типа, имели достоверно более низкий уровень креатинина на 2-й неделе госпитализации.
Заключение. У пациентов с COVID-19 среднетяжелого и тяжелого течения с сопутствующим CД 2 следует обращать особое внимание на сочетание высокого ИМТ и креатинина на 2-й неделе госпитализации, что является прогностически неблагоприятным предиктором летального исхода у данной категории больных.
Ключевые слова: COVID-19, сахарный диабет 2-го типа, ингибиторы дипептидилпептидазы-4, агонисты рецепторов глюкагоноподобного пептида-1, ингибиторы натрий-глюкозного котранспортера 2-го типа, креатинин
Materials and methods. A retrospective analysis of 291 case histories of patients with COVID-19 and T2DM hospitalized in the infection department of Semashko Regional Clinical Hospital from January to December 2021, including the main clinical and laboratory parameters.
Results. Among hospitalized patients with COVID-19, patients with T2DM had a higher mortality rate. An analysis of the case histories of deceased patients with COVID-19 and T2DM showed that at admission, body mass index (BMI), C-reactive protein, and creatinine were higher than those of survivors and amounted to BMI – 33 [30; 39] and 33 [28; 36] kg/m3; p=0.039, C-reactive protein – 77 [47.5; 106.0] and 57 [27.0; 89.0] mg/l; p=0.015, in terms of creatinine level – 89 [70.0; 144.0] and 82 [66.0; 101.0] µmol/l; p=0.039, respectively. It was found that in the second week of hospitalization in the group of deceased patients with COVID-19 and T2DM, the creatinine level was statistically significantly higher than in surviving patients and amounted to 94.5 [71.5; 141.0] and 72.5 [57.0; 88.0] µmol/L; p<0.001, respectively. The probability of death in hospitalized patients with type 2 COVID-19 and T2DM depended on BMI and creatinine levels at the second week of hospitalization. Patients with prehospital correction of hyperglycemia dipeptidyl peptidase-4 inhibitors/glucagon-like peptide-1 receptor agonists/sodium-glucose co-transporter 2 inhibitors had significantly lower creatinine levels at week 2 of hospitalization.
Conclusion. In patients with moderate to severe COVID-19 with concomitant T2DM, special attention should be paid to the combination of high BMI and creatinine in the second week of hospitalization, which is a prognostically unfavorable predictor of death in such patients.
Keywords: COVID-19, type 2 diabetes mellitus, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter 2 inhibitors, creatinine
Материалы и методы. Проведен ретроспективный анализ 291 истории болезни пациентов с COVID-19 и СД 2, госпитализированных в ГБУ РО «ОКБ им. Н.А. Семашко» с января по декабрь 2021 г., с включением основных клинико-лабораторных параметров.
Результаты. Среди госпитализированных больных COVID-19 пациенты с СД 2 имели более высокую летальность. Анализ историй болезни умерших пациентов с COVID-19 и СД 2 показал, что при поступлении показатели индекса массы тела (ИМТ), С-реактивного белка, креатинина были выше, чем у выживших, и составили соответственно: по ИМТ – 33 [30; 39] и 33 [28; 36] кг/м3; p=0,039, по уровню С-реактивного белка – 77 [47,5; 106,0] и 57 [27,0; 89,0] мг/л; p=0,015, по уровню креатинина – 89 [70,0; 144,0] и 82 [66,0; 101,0] мкмоль/л; р=0,039. Установлено, что на 2-й неделе госпитализации в группе умерших пациентов с COVID-19 и СД 2 уровень креатинина был статистически значимо выше, чем у выживших больных, и составил соответственно 94,5 [71,5; 141,0] и 72,5 [57,0; 88,0] мкмоль/л; p<0,001. Вероятность летального исхода у госпитализированных пациентов с COVID-19 и СД 2 зависела от ИМТ и уровня креатинина на 2-й неделе госпитализации. Пациенты с СД 2, которые на догоспитальном этапе принимали ингибиторы дипептидилпептидазы-4/агонисты рецепторов глюкагоноподобного пептида-1/ингибиторы натрий-глюкозного котранспортера 2-го типа, имели достоверно более низкий уровень креатинина на 2-й неделе госпитализации.
Заключение. У пациентов с COVID-19 среднетяжелого и тяжелого течения с сопутствующим CД 2 следует обращать особое внимание на сочетание высокого ИМТ и креатинина на 2-й неделе госпитализации, что является прогностически неблагоприятным предиктором летального исхода у данной категории больных.
Ключевые слова: COVID-19, сахарный диабет 2-го типа, ингибиторы дипептидилпептидазы-4, агонисты рецепторов глюкагоноподобного пептида-1, ингибиторы натрий-глюкозного котранспортера 2-го типа, креатинин
________________________________________________
Materials and methods. A retrospective analysis of 291 case histories of patients with COVID-19 and T2DM hospitalized in the infection department of Semashko Regional Clinical Hospital from January to December 2021, including the main clinical and laboratory parameters.
Results. Among hospitalized patients with COVID-19, patients with T2DM had a higher mortality rate. An analysis of the case histories of deceased patients with COVID-19 and T2DM showed that at admission, body mass index (BMI), C-reactive protein, and creatinine were higher than those of survivors and amounted to BMI – 33 [30; 39] and 33 [28; 36] kg/m3; p=0.039, C-reactive protein – 77 [47.5; 106.0] and 57 [27.0; 89.0] mg/l; p=0.015, in terms of creatinine level – 89 [70.0; 144.0] and 82 [66.0; 101.0] µmol/l; p=0.039, respectively. It was found that in the second week of hospitalization in the group of deceased patients with COVID-19 and T2DM, the creatinine level was statistically significantly higher than in surviving patients and amounted to 94.5 [71.5; 141.0] and 72.5 [57.0; 88.0] µmol/L; p<0.001, respectively. The probability of death in hospitalized patients with type 2 COVID-19 and T2DM depended on BMI and creatinine levels at the second week of hospitalization. Patients with prehospital correction of hyperglycemia dipeptidyl peptidase-4 inhibitors/glucagon-like peptide-1 receptor agonists/sodium-glucose co-transporter 2 inhibitors had significantly lower creatinine levels at week 2 of hospitalization.
Conclusion. In patients with moderate to severe COVID-19 with concomitant T2DM, special attention should be paid to the combination of high BMI and creatinine in the second week of hospitalization, which is a prognostically unfavorable predictor of death in such patients.
Keywords: COVID-19, type 2 diabetes mellitus, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter 2 inhibitors, creatinine
Полный текст
Список литературы
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15. Берстнева С.В., Шаханов А.В., Янкина С.В. Гены, кодирующие компоненты ренин-ангиотензиновой системы и факторы эндотелия, в развитии диабетической нефропатии при сахарном диабете 2 типа. Наука молодых (Eruditio Juvenium). 2018;6(3):420-8 [Berstneva SV, Shakhanov AV, Yankina SV. Genes coding for components of renin-angiotensin system and factors of endothelium and their role in development of diabetic nephropathy in type 2 diabetes mellitus. Science of the Young (Eruditio Juvenium). 2018;6(3):420-8 (in Russian)]. DOI:10.23888/HMJ201863420-428
16. Gao Y, Liu T, Zhong W, et al. Risk of metformin in patients with type 2 diabetes with COVID-19: A preliminary retrospective report. Clin Transl Sci. 2020;13(6):1055-9. DOI:10.1111/cts.12897
17. Marik PE, Bellomo R. Stress hyperglycemia: An essential survival response. Crit Care. 2013;17(2):305. DOI:10.1186/cc12514
18. Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): Clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust.
2020;213(2):54-6.e1. DOI:10.5694/mja2.50674
19. World Health Organization 4 September 2020. COVID-19: Scientific briefs. Responding to noncommunicable diseases during and beyond the COVID-19 pandemic: Policy brief. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Non-communicable_diseases-Policy_brief-2020.1. Accessed: 20.09.2023.
20. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364(9):829-41. DOI:10.1056/NEJMoa1008862
2. Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022;375(6585):1122-7. DOI:10.1126/science.abm8108
3. Akbariqomi M, Hosseini MS, Rashidiani J, et al. Clinical characteristics and outcome of hospitalized COVID-19 patients with diabetes: A single-center, retrospective study in Iran. Diabetes Res Clin Pract. 2020;169:108467. DOI:10.1016/j.diabres.2020.108467
4. Yang JK, Feng Y, Yuan MY, et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23(6):623-8. DOI:10.1111/j.1464-5491.2006.01861.x
5. Sorokina YuA, Sukhanov SA, Nikolaeva AA, et al. Hypoglycemic therapy in patients with type 2 diabetes mellitus and COVID-19. Effective Pharmacotherapy. 2022;18(6):10-9 (in Russian). DOI:10.33978/2307-3586-2022-18-6-10-19
6. Dedov II, Mokrysheva NG, Shestakova MV, et al. Glycemia control and choice of antihyperglycemic therapy in patients with type 2 diabetes mellitus and COVID-19: A consensus decision of the board of experts of the Russian association of endocrinologists. Diabetes Mellitus. 2022;25(1):27-49 (in Russian). DOI:10.14341/DM12873
7. Kotskaya AV, Salaychuk EV, Kudinov VI, et al. Variability of arterial pressure and cardiac rhythm in patients with coronary heart disease and diabetes mellitus: Effect of sodium-glucose co-transporter 2 inhibitor. I.P. Pavlov Russian Medical Biological Herald. 2021;29(4):489-96 (in Russian). DOI:10.17816/PAVLOVJ72376
8. Luo P, Qiu L, Liu Y, et al. Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis. Am J Trop Med Hyg. 2020;103(1):69-72. DOI:10.4269/ajtmh.20-0375
9. Solerte SB, D’Addio F, Trevisan R, et al. Sitagliptin treatment at the time of hospitalization was associated with reduced mortality in patients with type 2 diabetes and COVID-19: A multicenter case-control retrospective observational study. Diabetes Care. 2020;43(12):2999-3006. DOI:10.2337/dc20-1521
10. Abuhasira R, Ayalon-Dangur I, Zaslavsky N, et al. A randomized clinical trial of linagliptin vs. standard of care in patients hospitalized with diabetes and COVID-19. Front Endocrinol (Lausanne). 2021;12:794382. DOI:10.3389/fendo.2021.794382
11. Wargny M, Potier L, Gourdy P, et al. Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: Updated results from the nationwide CORONADO study. Diabetologia. 2021;64(4):778-94. DOI:10.1007/s00125-020-05351-w
12. Zhu Z, Zeng Q, Liu Q, et al. Association of glucose-lowering drugs with outcomes in patients with diabetes before hospitalization for COVID-19: A systematic review and network meta-analysis. JAMA Netw Open. 2022;5(12):e2244652. DOI:10.1001/jamanetworkopen.2022.44652
13. Shestakova MV, Vikulova OK, Isakov MA, Dedov II. Diabetes and COVID-19: Analysis of the clinical outcomes according to the data of the Russian Diabetes Registry. Problems of Endocrinology. 2020;66(1):35-46 (in Russian). DOI:10.14341/probl12458
14. Gupta R, Ghosh A, Singh AK, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes Metab Syndr. 2020;14(3):211-2. DOI:10.1016/j.dsx.2020.03.002
15. Berstneva SV, Shakhanov AV, Yankina SV. Genes coding for components of renin-angiotensin system and factors of endothelium and their role in development of diabetic nephropathy in type 2 diabetes mellitus. Science of the Young (Eruditio Juvenium). 2018;6(3):420-8 (in Russian). DOI:10.23888/HMJ201863420-428
16. Gao Y, Liu T, Zhong W, et al. Risk of metformin in patients with type 2 diabetes with COVID-19: A preliminary retrospective report. Clin Transl Sci. 2020;13(6):1055-9. DOI:10.1111/cts.12897
17. Marik PE, Bellomo R. Stress hyperglycemia: An essential survival response. Crit Care. 2013;17(2):305. DOI:10.1186/cc12514
18. Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): Clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust.
2020;213(2):54-6.e1. DOI:10.5694/mja2.50674
19. World Health Organization 4 September 2020. COVID-19: Scientific briefs. Responding to noncommunicable diseases during and beyond the COVID-19 pandemic: Policy brief. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Non-communicable_diseases-Policy_brief-2020.1. Accessed: 20.09.2023.
20. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364(9):829-41. DOI:10.1056/NEJMoa1008862
2. Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022;375(6585):1122-7. DOI:10.1126/science.abm8108
3. Akbariqomi M, Hosseini MS, Rashidiani J, et al. Clinical characteristics and outcome of hospitalized COVID-19 patients with diabetes: A single-center, retrospective study in Iran. Diabetes Res Clin Pract. 2020;169:108467. DOI:10.1016/j.diabres.2020.108467
4. Yang JK, Feng Y, Yuan MY, et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23(6):623-8. DOI:10.1111/j.1464-5491.2006.01861.x
5. Сорокина Ю.А., Суханов С.А., Николаева А.А., и др. Сахароснижающая терапия у больных сахарным диабетом 2 типа и COVID-19. Эффективная фармакотерапия. 2022;18(6):10-9 [Sorokina YuA, Sukhanov SA, Nikolaeva AA, et al. Hypoglycemic therapy in patients with type 2 diabetes mellitus and COVID-19. Effective Pharmacotherapy. 2022;18(6):10-9 (in Russian)]. DOI:10.33978/2307-3586-2022-18-6-10-19
6. Дедов И.И., Мокрышева Н.Г., Шестакова М.В., и др. Контроль гликемии и выбор антигипергликемической терапии у пациентов с сахарным диабетом 2 типа и COVID-19: консенсусное решение совета экспертов Российской ассоциации эндокринологов. Сахарный диабет. 2022;25(1):27-49 [Dedov II, Mokrysheva NG, Shestakova MV, et al. Glycemia control and choice of antihyperglycemic therapy in patients with type 2 diabetes mellitus and COVID-19: A consensus decision of the board of experts of the Russian association of endocrinologists. Diabetes Mellitus. 2022;25(1):27-49 (in Russian)]. DOI:10.14341/DM12873
7. Коцкая А.В., Салайчук Е.В., Кудинов В.И., и др. Вариабельность артериального давления и ритма сердца у больных с ишемической болезнью сердца и сахарным диабетом, влияние ингибитора натрийглюкозного ко-транспортера 2 типа. Российский медико-биологический вестник им. академика И.П. Павлова. 2021;29(4):489-96 [Kotskaya AV, Salaychuk EV, Kudinov VI, et al. Variability of arterial pressure and cardiac rhythm in patients with coronary heart disease and diabetes mellitus: Effect of sodium-glucose co-transporter 2 inhibitor. I.P. Pavlov Russian Medical Biological Herald. 2021;29(4):489-96 (in Russian)]. DOI:10.17816/PAVLOVJ72376
8. Luo P, Qiu L, Liu Y, et al. Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis. Am J Trop Med Hyg. 2020;103(1):69-72. DOI:10.4269/ajtmh.20-0375
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2020;213(2):54-6.e1. DOI:10.5694/mja2.50674
19. World Health Organization 4 September 2020. COVID-19: Scientific briefs. Responding to noncommunicable diseases during and beyond the COVID-19 pandemic: Policy brief. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Non-communicable_diseases-Policy_brief-2020.1. Accessed: 20.09.2023.
20. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364(9):829-41. DOI:10.1056/NEJMoa1008862
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2. Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022;375(6585):1122-7. DOI:10.1126/science.abm8108
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5. Sorokina YuA, Sukhanov SA, Nikolaeva AA, et al. Hypoglycemic therapy in patients with type 2 diabetes mellitus and COVID-19. Effective Pharmacotherapy. 2022;18(6):10-9 (in Russian). DOI:10.33978/2307-3586-2022-18-6-10-19
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8. Luo P, Qiu L, Liu Y, et al. Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis. Am J Trop Med Hyg. 2020;103(1):69-72. DOI:10.4269/ajtmh.20-0375
9. Solerte SB, D’Addio F, Trevisan R, et al. Sitagliptin treatment at the time of hospitalization was associated with reduced mortality in patients with type 2 diabetes and COVID-19: A multicenter case-control retrospective observational study. Diabetes Care. 2020;43(12):2999-3006. DOI:10.2337/dc20-1521
10. Abuhasira R, Ayalon-Dangur I, Zaslavsky N, et al. A randomized clinical trial of linagliptin vs. standard of care in patients hospitalized with diabetes and COVID-19. Front Endocrinol (Lausanne). 2021;12:794382. DOI:10.3389/fendo.2021.794382
11. Wargny M, Potier L, Gourdy P, et al. Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: Updated results from the nationwide CORONADO study. Diabetologia. 2021;64(4):778-94. DOI:10.1007/s00125-020-05351-w
12. Zhu Z, Zeng Q, Liu Q, et al. Association of glucose-lowering drugs with outcomes in patients with diabetes before hospitalization for COVID-19: A systematic review and network meta-analysis. JAMA Netw Open. 2022;5(12):e2244652. DOI:10.1001/jamanetworkopen.2022.44652
13. Shestakova MV, Vikulova OK, Isakov MA, Dedov II. Diabetes and COVID-19: Analysis of the clinical outcomes according to the data of the Russian Diabetes Registry. Problems of Endocrinology. 2020;66(1):35-46 (in Russian). DOI:10.14341/probl12458
14. Gupta R, Ghosh A, Singh AK, Misra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes Metab Syndr. 2020;14(3):211-2. DOI:10.1016/j.dsx.2020.03.002
15. Berstneva SV, Shakhanov AV, Yankina SV. Genes coding for components of renin-angiotensin system and factors of endothelium and their role in development of diabetic nephropathy in type 2 diabetes mellitus. Science of the Young (Eruditio Juvenium). 2018;6(3):420-8 (in Russian). DOI:10.23888/HMJ201863420-428
16. Gao Y, Liu T, Zhong W, et al. Risk of metformin in patients with type 2 diabetes with COVID-19: A preliminary retrospective report. Clin Transl Sci. 2020;13(6):1055-9. DOI:10.1111/cts.12897
17. Marik PE, Bellomo R. Stress hyperglycemia: An essential survival response. Crit Care. 2013;17(2):305. DOI:10.1186/cc12514
18. Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): Clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust.
2020;213(2):54-6.e1. DOI:10.5694/mja2.50674
19. World Health Organization 4 September 2020. COVID-19: Scientific briefs. Responding to noncommunicable diseases during and beyond the COVID-19 pandemic: Policy brief. Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Non-communicable_diseases-Policy_brief-2020.1. Accessed: 20.09.2023.
20. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011;364(9):829-41. DOI:10.1056/NEJMoa1008862
Авторы
Е.А. Карасева*1, В.А. Мартынов1, Т.Е. Филатова1, В.В. Малеев2, В.Ю. Гришин3, Н.С. Пронин1, Е.И. Вербицкая1, В.И. Попова1
1ФГБОУ ВО «Рязанский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, Рязань, Россия;
2ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора, Москва, Россия;
3ГБУ РО «Областная клиническая больница им. Н.А. Семашко», Рязань, Россия
*ekar83@gmail.com
1Pavlov Ryazan State Medical University, Ryazan, Russia;
2Central Research Institute of Epidemiology, Moscow, Russia;
3Semashko Regional Clinical Hospital, Ryazan, Russia
*ekar83@gmail.com
1ФГБОУ ВО «Рязанский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, Рязань, Россия;
2ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора, Москва, Россия;
3ГБУ РО «Областная клиническая больница им. Н.А. Семашко», Рязань, Россия
*ekar83@gmail.com
________________________________________________
1Pavlov Ryazan State Medical University, Ryazan, Russia;
2Central Research Institute of Epidemiology, Moscow, Russia;
3Semashko Regional Clinical Hospital, Ryazan, Russia
*ekar83@gmail.com
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