Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021; 20: 89-99
Особенности течения новой коронавирусной инфекции COVID-19 у детей с онкологическими, онкогематологическими и тяжелыми иммунологическими заболеваниями. Опыт НМИЦ ДГОИ им. Дмитрия Рогачева
https://doi.org/10.24287/1726-1708-2021-20-4-89-99Аннотация
Учитывая недостаточное количество данных по течению COVID-19 у иммунокомпрометированных детей на территории Российской Федерации, в ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России (Центр) было проведено исследование, посвященное изучению особенностей клиники, факторов риска и исходов новой коронавирусной инфекции у детей с онкогематологическими заболеваниями. В ретроспективно-проспективное, нерандомизированное и неинтервенционное исследование были включены дети до 18 лет с онкологическими, онкогематологическими заболеваниями, а также с первичными иммунодефицитными синдромами (ПИДС), проходившие лечение в Центре с апреля 2020 г. по октябрь 2021 г. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Инфекция COVID-19 была установлена методом полимеразной цепной реакции и классифицирована на бессимптомную, легкую, среднетяжелую, тяжелую и крайне тяжелую формы. В исследование включены 89 пациентов с медианой возраста 9,7 года и практически равным соотношением мальчиков и девочек (1,1:1). Преимущественно инфицирование пациентов происходило в семейном кластере (74%). Основными заболеваниями были гемобластозы (43,8%), солидные опухоли (33,7%), ПИДС (14,6%). Наиболее частыми клиническими проявлениями были лихорадка (29%) и респираторная симптоматика (47%). В 79% случаев новая коронавирусная инфекция протекала бессимптомно или в легкой форме, тогда как в 21% в среднетяжелой (16%) и тяжелой (5%) формах. Факторами, коррелирующими с развитием тяжелых форм заболевания, были лимфопения (р < 0,001) и проведение трансплантации гемопоэтических стволовых клеток (ТГСК) (р = 0,002). Излечение от новой коронавирусной инфекции отмечалось у 84% пациентов, 16% больных умерли, однако к смерти непосредственно от COVID-19 было отнесено 5,5% случаев. Высокий уровень смертности отмечался у пациентов со среднетяжелым/тяжелым течением COVID-19 (47% против 7%, р < 0,001), прогрессией/рецидивом основного заболевания (36,3% против 6%, р = 0,02), у получавших специфическую терапию в течение года до инфицирования SARS-CoV-2 (21% против 0%, р = 0,02), у реципиентов ТГСК (31,6% против 12,1%, р = 0,02), при сочетанном инфекционном процессе (33% против 9,2%, р < 0,01). Преимущественно COVID-19 у иммунокомпрометированных детей протекает в бессимптомной или легкой формах. Факторами, ассоциированными с тяжелым течением и неблагоприятным прогнозом, явились среднетяжелое и тяжелое течение COVID-19, рецидив/прогрессия основного заболевания, проведение специфической терапии, в первую очередь ТГСК, в течение года до инфицирования SARS-CoV-2, сочетанный инфекционный процесс и лимфопения. Полученные в исследовании данные могут быть полезны при принятии решения о тактике ведения пациентов.
Список литературы
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8. Haesler G.M., Amman R.A., Carlesse F., Groll A.H., Averbuch D., Costagnola E., et al. SARS-CoV-2 in children with cancer or following haematopoietic stem cell transplant: an analysis of 131 patients. Eur J Cancer 2021; 159: 78–86.
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14. Connelly J.A., Chong H., Esbenshade A.J., Frame D., Failing С., Secord Е., Walkovich K. Impact of COVID-19 on Pediatric Immunocompromised Patients. Pediatr Clin North Am 2021; 68 (5): 1029–54.
15. Bailey Ch., Razzaghi H., Burrows E., Bunnell T., Camacho P., Christakis D., et al. Assessment of 135 794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 Across the United States. JAMA Pediatrics 2021; 175 (2): 176–84.
16. Zimmermann P., Curtis N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch Dis Child 2021; 106: 429–39.
17. André N., Rouger‐Gaudichon J., Brethon B., Phulpin A., Thebault E., Pertuisel S., Gardemer V. COVID‐19 in pediatric oncology from French pediatric oncology and hematology centers: High risk of severe forms? Pediatr Blood Cancer 2020; 67: e28392.
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19. D’Antiga L. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver Transpl 2020; 26 (6): 832–4.
20. Parsons S., Tran V.L. The Trilogy of SARS-CoV-2 in Pediatrics (Part 1): Acute COVID-19 in Special Populations. J Pediatr Pharmacol Ther 2021; 26 (3): 220–39. DOI: 10.5863/1551-6776-26.3.220
21. Hammad M., Shalaby L., Sidhom I., Sherief N., Abdo I., Soliman S., et al. Management and Outcome of Coronavirus Disease 2019 (COVID-19) in Pediatric Cancer Patients: A Single Centre Experience from a Developing Country. Clin Lymphoma Myeloma Leuk 2021; 21 (11): e853–64.
22. Ljungman P., de la Camara R., Mikulska M., Tridello G., Aguado B., Zahrani M.A., et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia 2021; 35 (10): 2885–94.
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24. Vijenthira A., Gong I., Fox T., Booth S., Cook G., Fattizzo B., et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood 2020; 136 (25): 2881–92.
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27. Stokes C.L., Patel P.A., Sabnis H.S., Mitchell S.G., Yildirim I.B., Pauly M.G. Severe COVID-19 disease in two pediatric oncology patients. Pediatr Blood Cancer 2020; 67: e28432.
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30. Временные методические рекомендации Министерства здравоохранения Российской Федерации: Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Версия 13.1 от 17.11.2021. [Электронный ресурс] URL: https:// static-0.minzdrav.gov.ru/system/attachments/attaches/000/058/392/original/%D0%92%D0%9C%D0%A0-13.1-from-17-11-2021.pdf. Дата обращения 08.12.2021.
31. Balashov D., Trakhtman P., Livshits A., Kovalenko I., Tereshenko G., Solopova G., et al. SARS-CoV-2 convalescent plasma therapy in pediatric patient after hematopoietic stem cell transplantation. Transfus Apher Sci 2021; 60: 102983.
Pediatric Hematology/Oncology and Immunopathology. 2021; 20: 89-99
The novel coronavirus disease (COVID-19) in children with cancer, hematologic malignancies, and severe immunodeficiencies. Results of monocenter study
https://doi.org/10.24287/1726-1708-2021-20-4-89-99Abstract
Data on clinical manifestations of COVID-19 in immunocompromised patients in Russia is lacking, which prompted us to conduct a study to investigate clinical manifestations, risk factors, and outcomes of SARS-CoV-2 infection in children with oncological and hematological diseases treated at the D. Rogachev NMRCPHOI (Center). In this retrospective-prospective, nonrandomized, non-interventional study we enrolled children under 18 years with cancer, hematologic malignancies, and primary immunodeficiencies (PIDs) who underwent treatment at the Center from April 2020 to October 2021. COVID-19 cases were confirmed by polymerase chain reaction testing and classified as asymptomatic, mild, moderate, severe and critical. The study was approved by the Independent Ethics Committee and the Scientific Council of the Center. The study included 89 patients with a median age of 9.7 years and almost equal gender distribution (the male-to-female ratio was 1.1:1). Most patients (74%) were infected in a family claster. The main underlying diseases were: hemoblastoses (43.8%), solid tumors (33.7%), PIDs (14.6%). The most common clinical symptoms were fever (29%) and respiratory symptoms (47%). In 79% of cases, patients were asymptomatic or had mild symptoms; 21% of patients had moderate and severe disease (16% and 5%, accordingly). Risk factors associated with severe COVID-19 included lymphopenia (p < 0.001) and hematopoietic stem cell transplantation (HSCT) (p = 0.002). Full recovery was documented in 84% of the patients, 16% died, however COVID-attributed mortality was 5.5%. The highest mortality was in patients with moderate/severe COVID-19 (47% vs 7%, p < 0.001), in those with progression/ relapse of the underlying disease (36.3% vs 6%, p = 0.02), in children who had received specific therapy within a year before the SARS-CoV-2 diagnosis (21% vs 0%, p = 0.02), among HSCT recipients (31.6% vs 12.1%, p = 0.02), and patients with concomitant infections (33% vs 9.2%, p < 0.01). Factors associated with poor prognosis were moderate or severe COVID-19, relapse/ progression of the underlying disease, specific treatment (HSCT in particular) within 1 year before the SARS-CoV-2 diagnosis, concomitant infections, and lymphopenia. Data obtained in this study can help physicians with management decisions at this population of patients.
References
1. Vsemirnaya organizatsiya zdravookhraneniya. Pandemiya koronavirusnogo zabolevaniya (COVID19). [Elektronnyi resurs] URL: https://www.euro.who.int/ru/health-topics/health-emergencies/coronavirus-covid-19. Data obrashcheniya 08.12.2021.
2. Dong Y., Mo X., Hu Y., Qi X., Jiang F., Jiang Zh., Tong S. Epidemiology of COVID-19 among children in China. Pediatrics 2020; 145 (6): 1–10.
3. Rajapakse N., Dixit D. Human and novel coronavirus infections in children: a review. Paediatr Int Child Health 2021; 41 (1): 36–55.
4. CDC COVID19 Response Team. Coronavirus Disease 2019 in Children – United States, February 12 – April 2, 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (14): 422–6.
5. Vremennye metodicheskie rekomendatsii Ministerstva zdravookhraneniya Rossiiskoi Federatsii: Profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii (COVID-19). Versiya 8 ot 3.09.2020. [Elektronnyi resurs] URL: https:// static-0.minzdrav.gov.ru/system/attachments/attaches/000/051/777/original/030902020_COVID-19_v8.pdf. Data obrashcheniya 08.12.2021.
6. Hoang A., Chorath K., Moreira A., Evans M., Burmeister-Morton F., Burmeister F., et al. COVID-19 in 7780 pediatric patients: A systematic review. EClinicalMedicine 2020; 24: 100433.
7. Chan J.F.-W., Yuan S., Kok K.-H., To K., Chu H., Jang J., et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395: 514–23.
8. Haesler G.M., Amman R.A., Carlesse F., Groll A.H., Averbuch D., Costagnola E., et al. SARS-CoV-2 in children with cancer or following haematopoietic stem cell transplant: an analysis of 131 patients. Eur J Cancer 2021; 159: 78–86.
9. Lu Y., Li Y., Deng W., Liu M., He Y., Huang L., et al. Symptomatic infection is associated with prolonged duration of viral shedding in mild coronavirus disease 2019: a retrospective study of 110 children in Wuhan. Pediatr Infect Dis J 2020; 39 (7): e95–9.
10. Lu X., Zhang L., Du H., Jiang Zh., Li Y., Qu J., et al. SARS‐CoV‐2 infection in children. N Engl J Med 2020; 382: 1663–5.
11. Kuczborska K., Książyk J. Prevalence and Course of SARS-CoV-2 Infection among Immunocompromised Children Hospitalised in the Tertiary Referral Hospital in Poland. J Clin Med 2021; 10 (19): 4556.
12. Ji L.-N., Chao S., Wang Y.-J., Li X.-J., Mu X.-D., Lin M.-G., et al. Clinical features of pediatric patients with COVID-19: a report of two family cluster cases. World J Pediatr 2020; 16 (3): 267–70.
13. Wei M., Yuan J., Liu Y., Fu T., Yu X., Zhang Z.-J. Novel coronavirus infection in hospitalized infants under 1 year of age in China. JAMA 2020; 323: 1313–4.
14. Connelly J.A., Chong H., Esbenshade A.J., Frame D., Failing S., Secord E., Walkovich K. Impact of COVID-19 on Pediatric Immunocompromised Patients. Pediatr Clin North Am 2021; 68 (5): 1029–54.
15. Bailey Ch., Razzaghi H., Burrows E., Bunnell T., Camacho P., Christakis D., et al. Assessment of 135 794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 Across the United States. JAMA Pediatrics 2021; 175 (2): 176–84.
16. Zimmermann P., Curtis N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch Dis Child 2021; 106: 429–39.
17. André N., Rouger‐Gaudichon J., Brethon B., Phulpin A., Thebault E., Pertuisel S., Gardemer V. COVID‐19 in pediatric oncology from French pediatric oncology and hematology centers: High risk of severe forms? Pediatr Blood Cancer 2020; 67: e28392.
18. Hrusak O., Kalina T., Wolf J., Balduzzi A., Provenzi M., Rizzari C., Rizzari S., et al. Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment. Eur J Cancer 2020; 132: 11–6.
19. D’Antiga L. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver Transpl 2020; 26 (6): 832–4.
20. Parsons S., Tran V.L. The Trilogy of SARS-CoV-2 in Pediatrics (Part 1): Acute COVID-19 in Special Populations. J Pediatr Pharmacol Ther 2021; 26 (3): 220–39. DOI: 10.5863/1551-6776-26.3.220
21. Hammad M., Shalaby L., Sidhom I., Sherief N., Abdo I., Soliman S., et al. Management and Outcome of Coronavirus Disease 2019 (COVID-19) in Pediatric Cancer Patients: A Single Centre Experience from a Developing Country. Clin Lymphoma Myeloma Leuk 2021; 21 (11): e853–64.
22. Ljungman P., de la Camara R., Mikulska M., Tridello G., Aguado B., Zahrani M.A., et al. COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey. Leukemia 2021; 35 (10): 2885–94.
23. St. Jude, SIOP Global COVID-19 registry. [Elektronnyi resurs] URL: https://global.stjude.org/en-us/global-covid-19-observatory-and-resource-center-for-childhood-cancer/registry.html. Data obrashcheniya 08.12.2021.
24. Vijenthira A., Gong I., Fox T., Booth S., Cook G., Fattizzo B., et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood 2020; 136 (25): 2881–92.
25. Hanna T.P., Evans G.A., Booth C.M. Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic. Nat Rev Clin Oncol 2021; 17 (5): 268–70.
26. Oz-Alcalay L., Elitzur S., Amitai N., Toledano H., Barzilai-Birenboim S., Avrahami G., et al.. COVID-19 infection in pediatric patients treated for cancer. Int J Clin Oncol 2021: 1–7.
27. Stokes C.L., Patel P.A., Sabnis H.S., Mitchell S.G., Yildirim I.B., Pauly M.G. Severe COVID-19 disease in two pediatric oncology patients. Pediatr Blood Cancer 2020; 67: e28432.
28. Hamdy R., El-Mahallawy H., Ebeid E. COVID-19 infection in febrile neutropenic pediatric hematology oncology patients. Pediatr Blood Cancer 2021; 68: e28765.
29. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. [Elektronnyi resurs] URL: https://www. covid19treatmentguidelines.nih.gov/. Data obrashcheniya 08.12.2021.
30. Vremennye metodicheskie rekomendatsii Ministerstva zdravookhraneniya Rossiiskoi Federatsii: Profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii (COVID-19). Versiya 13.1 ot 17.11.2021. [Elektronnyi resurs] URL: https:// static-0.minzdrav.gov.ru/system/attachments/attaches/000/058/392/original/%D0%92%D0%9C%D0%A0-13.1-from-17-11-2021.pdf. Data obrashcheniya 08.12.2021.
31. Balashov D., Trakhtman P., Livshits A., Kovalenko I., Tereshenko G., Solopova G., et al. SARS-CoV-2 convalescent plasma therapy in pediatric patient after hematopoietic stem cell transplantation. Transfus Apher Sci 2021; 60: 102983.
