Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지
DOI QR코드

DOI QR Code

Overview of management of children with COVID-19

  • 투고 : 2020.05.17
  • 심사 : 2020.07.10
  • 발행 : 2020.09.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The widespread and contagious coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has become a burden in the global health domain. The subsequent discovery of the virus features and pathogenesis, and prompt and adequate management are still lacking and remain inconclusive. Children usually present milder symptoms than adults, and management focuses on providing symptomatic and respiratory supports. Several treatment modalities, including the utilization of mechanical ventilation (MV), antivirals, immune-modulating drugs, or other agents, may present promising results in reducing the symptoms of COVID-19, particularly in severe cases. Although no randomized clinical trials have been published to date, it is interesting to explore potential modalities for treating COVID-19 in children, based on review articles, case reports, and recent guidelines.

키워드

참고문헌

  1. Wu YC, Chen CS, Chan YJ. The outbreak of COVID-19: an overview. J Chin Med Assoc 2020;83:217-20. https://doi.org/10.1097/jcma.0000000000000270
  2. World Health Organization. Novel coronavirus (2019-nCoV) situation report - 1 [Internet]. Geneva (Switzerland): World Health Organization; 2020 [cited 2020 May 24]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
  3. World Health Organization. IHR Emergency Committee on Novel Coronavirus (2019-nCoV) [Internet]. Geneva (Switzerland): World Health Organization; 2020 [cited 2020 May 10]. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-statement-onihr-emergency-committee-on-novel-coronavirus-(2019-ncov).
  4. World Health Organization. Coronavirus disease COVID-2019: situation report - 162 [Internet]. Geneva (Switzerland): World Health Organization; 2020 [cited 2020 May 10]. Available from: https://www.who.int/docs/default-source/coronaviruse/20200630-covid-19-sitrep-162.pdf?sfvrsn=e00a5466_2.
  5. Park SE. Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; coronavirus disease-19). Clin Exp Pediatr 2020;63:119-24. https://doi.org/10.3345/cep.2020.00493
  6. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382:727-33. https://doi.org/10.1056/NEJMoa2001017
  7. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of 2019 novel coronavirus diseases (COVID-19) in Jingmen, China. China CDC Wkly 2020;2:113-22. https://doi.org/10.46234/ccdcw2020.032
  8. World Health Organization. Novel coronavirus [Internet]. Geneva (Switzerland): World Health Organization; 2020 [cited 2020 May 10]. Available from: https://www.who.int/csr/don/12-january-2020-novelcoronavirus-china/en/.
  9. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet 2020;395:470-3. https://doi.org/10.1016/s0140-6736(20)30185-9
  10. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr 2020;109:1088-95. https://doi.org/10.1111/apa.15270
  11. Xu Y, Li X, Zhu B, Liang H, Fang C, Gong Y, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med 2020;26:502-5. https://doi.org/10.1038/s41591-020-0817-4
  12. Shekerdemian LS, Mahmood NR, Wolfe KK, Riggs BJ, Ross CE, McKiernan CA, et al. Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian pediatric intensive care units. JAMA Pediatr 2020 May 11 [Epub]. https://doi.org/10.1001/jamapediatrics.2020.1948.
  13. Choi SH, Kim HW, Kang JM, Kim DH, Cho EY. Epidemiology and clinical features of coronavirus disease 2019 in children. Clin Exp Pediatr 2020;63:125-32. https://doi.org/10.3345/cep.2020.00535
  14. Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis 2020;20:689-96. https://doi.org/10.1016/s1473-3099(20)30198-5
  15. Dhochak N, Singhal T, Kabra SK, Lodha R. Pathophysiology of COVID-19: why children fare better than adults? Indian J Pediatr 2020;87:537-46. https://doi.org/10.1007/s12098-020-03322-y
  16. Cristiani L, Mancino E, Matera L, Nenna R, Pierangeli A, Scagnolari C, et al. Will children reveal their secret? The coronavirus dilemma. Eur Respir J 2020;55:2000749. https://doi.org/10.1183/13993003.00749-2020
  17. Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J Pediatr 2020;16:251-9. https://doi.org/10.1007/s12519-020-00354-4
  18. Saheb Sharif-Askari N, Saheb Sharif-Askari F, Alabed M, Temsah MH, Al Heialy S, Hamid Q, et al. Airways expression of SARS-CoV-2 receptor, ACE2, and TMPRSS2 is lower in children than adults and increases with smoking and COPD. Mol Ther Methods Clin Dev 2020;18:1-6. https://doi.org/10.1016/j.omtm.2020.05.013
  19. Cao Q, Chen YC, Chen CL, Chiu CH. SARS-CoV-2 infection in children: transmission dynamics and clinical characteristics. J Formos Med Assoc 2020;119:670-3. https://doi.org/10.1016/j.jfma.2020.02.009
  20. Lyu J, Miao T, Dong J, Cao R, Li Y, Chen Q. Reflection on lower rates of COVID-19 in children: does childhood immunizations offer unexpected protection? Med Hypotheses 2020;143:109842. https://doi.org/10.1016/j.mehy.2020.109842
  21. Carsetti R, Quintarelli C, Quinti I, Piano Mortari E, Zumla A, Ippolito G, et al. The immune system of children: the key to understanding SARSCoV- 2 susceptibility? Lancet Child Adolesc Health 2020;4:414-6. https://doi.org/10.1016/S2352-4642(20)30135-8
  22. Niewiesk S. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol 2014;5:446. https://doi.org/10.3389/fimmu.2014.00446
  23. Chiotos K, Hayes M, Kimberlin DW, Jones SB, James SH, Pinninti SG, et al. Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2. J Pediatric Infect Dis Soc 2020 Apr 22:piaa045. https://doi.org/10.1093/jpids/piaa045. [Epub].
  24. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating personto-person transmission: a study of a family cluster. Lancet 2020;395:514-23. https://doi.org/10.1016/s0140-6736(20)30154-9
  25. Liu W, Zhang Q, Chen J, Xiang R, Song H, Shu S, et al. Detection of COVID-19 in Children in Early January 2020 in Wuhan, China. N Engl J Med 2020;382:1370-1. https://doi.org/10.1056/NEJMc2003717
  26. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. N Engl J Med 2020;382:1663-5. https://doi.org/10.1056/NEJMc2005073
  27. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics 2020. https://doi.org/10.1542/peds.2020-0702.
  28. CDC COVID-19 Response Team. Coronavirus disease 2019 in children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:422-6. https://doi.org/10.15585/mmwr.mm6914e4
  29. Parri N, Lenge M, Buonsenso D; Coronavirus Infection in Pediatric Emergency Departments (CONFIDENCE) Research Group. Children with COVID-19 in Pediatric Emergency Departments in Italy. N Engl J Med 2020;383:187-90. https://doi.org/10.1056/NEJMc2007617
  30. Gugus Tugas Percepatan Penanganan COVID-19. Data sebaran kasus COVID-19 [Internet]. Jakarta (Indonesia): Gugus Tugas Percepatan Penanganan COVID-19; 2020 [cited 2020 Jul 1]. Available from: https://www. covid19.go.id/.
  31. Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R, et al. Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement. World J Pediatr 2020;16:223-31. https://doi.org/10.1007/s12519-020-00343-7
  32. Rahimzadeh G, Noghabi ME, Elyaderani FK, Navaeifar MR, Enayati AA, Anari AM, et al. COVID-19 infection in iranian children: a case series of 9 patients. J Pediatr Rev 2020;139-44.
  33. Cai J, Xu J, Lin D, Yang Z, Xu L, Qu Z, et al. A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis 2020 Feb 28:ciaa198. https://doi.org/10.1093/cid/ciaa198.
  34. World Health Organization. Clinical management of COVID-19: interim guidance, 27 May 2020. Geneva (Switzerland): World Health Organization; 2020.
  35. Garcia-Salido A, Leoz-Gordillo I, Martinez de Azagra-Garde A, Nieto-Moro M, Iglesias-Bouzas MI, Garcia-Teresa MA, et al. Children in critical care due to severe acute respiratory syndrome coronavirus 2 infection: experience in a Spanish Hospital. Pediatr Crit Care Med 2020 May 27:10.1097/PCC.0000000000002475. https://doi.org/10.1097/PCC.0000000000002475.
  36. Carlotti APCP, Carvalho WB, Johnston C, Rodriguez IS, Delgado AF. COVID-19 Diagnostic and Management Protocol for Pediatric Patients. Clinics (Sao Paulo) 2020;75:e1894. https://doi.org/10.6061/clinics/2020/e1894
  37. Chen ZM, Fu JF, Shu Q, Chen YH, Hua CZ, Li FB, et al. Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus. World J Pediatr 2020;16:240-6. https://doi.org/10.1007/s12519-020-00345-5
  38. Wang Y, Zhu LQ. Pharmaceutical care recommendations for antiviral treatments in children with coronavirus disease 2019. World J Pediatr 2020;16:271-4. https://doi.org/10.1007/s12519-020-00353-5
  39. Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, et al. Treatment with interferon-${\alpha}2b$ and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 2013;19:1313-7. https://doi.org/10.1038/nm.3362
  40. Lou XX, Shi CX, Zhou CC, Tian YS. Three children who recovered from novel coronavirus 2019 pneumonia. J Paediatr Child Health 2020;56:650-1. https://doi.org/10.1111/jpc.14871
  41. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA 2020 Apr 13 [Epub]. https://doi.org/10.1001/jama.2020.6019.
  42. Kang CK, Seong MW, Choi SJ, Kim TS, Choe PG, Song SH, et al. In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses. Korean J Intern Med 2020;35:782-7. https://doi.org/10.3904/kjim.2020.157
  43. Zimmermann P, Curtis N. Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr Infect Dis J 2020;39:355-68. https://doi.org/10.1097/INF.0000000000002660
  44. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269-71. https://doi.org/10.1038/s41422-020-0282-0
  45. US Food and Drug Administration. FDA issues emergency use authorization for potential COVID-19 treatment [Internet]. Silver Spring (MD): US Food and Drug Administration; 2020 [cited 2020 Jun 10]. Available from: https://www.fda.gov/media/137566/download.
  46. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020;382:2327-36. https://doi.org/10.1056/NEJMoa2007016
  47. Kadam RU, Wilson IA. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc Natl Acad Sci U S A 2017;114:206-14. https://doi.org/10.1073/pnas.1617020114
  48. Indonesian Pediatric Society. Panduan Klinis Tata Laksana COVID-19 pada Anak. Jakarta (Indonesia): Indonesian Pediatric Society, 2020.
  49. Burhan E, Susanto AD, Nasution SA, Ginanjar E, Pitoyo CW, Susilo A, et al. Jakarta (Indonesia): Perhimpunan Dokter Paru Indonesia (PDPI) Perhimpunan Dokter Spesialis Kardiovaskular Indonesia (PERKI) Perhimpunan Dokter Spesialis Penyakit Dalam Indonesia (PAPDI) Perhimpunan Dokter Anestesiologi dan Terapi Intensif Indonesia (PERDATIN) Ikatan Dokter Anak Indonesia (IDAI), 2020.
  50. Hedrich CM. COVID-19 - considerations for the paediatric rheumatologist. Clin Immunol 2020;214:108420. https://doi.org/10.1016/j.clim.2020.108420
  51. Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, Kernan KF, et al. On the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol 2020;72:1059-63. https://doi.org/10.1002/art.41285
  52. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 2020;53:25-32. https://doi.org/10.1016/j.cytogfr.2020.05.003
  53. Shi Y, Tan M, Chen X, Liu Y, Huang J, Ou J, et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China. medRxiv 2020.03.12.20034736. https://doi.org/10.1101/2020.03.12.20034736.
  54. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the Cytokine Storm' in COVID-19. J Infect 2020;80:607-13. https://doi.org/10.1016/j.jinf.2020.03.037
  55. Lee KY, Rhim JW, Kang JH. Early preemptive immunomodulators (Corticosteroids) for severe pneumonia patients infected with SARSCOV-2. Clin Exp Pediatr 2020;63:117-8. https://doi.org/10.3345/cep.2020.00290
  56. Li H, Chen C, Hu F, Wang J, Zhao Q, Gale RP, et al. Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARSCoV, or MERS-CoV infection: a systematic review and meta-analysis. Leukemia 2020;34:1503-11. https://doi.org/10.1038/s41375-020-0848-3
  57. Ahn JY, Sohn Y, Lee SH, Cho Y, Hyun JH, Baek YJ, et al. Use of convalescent plasma therapy in two COVID-19 patients with acute respiratory distress syndrome in Korea. J Korean Med Sci 2020;35:e149. https://doi.org/10.3346/jkms.2020.35.e149
  58. Gasparyan AY, Misra DP, Yessirkepov M, Zimba O. Perspectives of immune therapy in coronavirus disease 2019. J Korean Med Sci 2020;35:e176. https://doi.org/10.3346/jkms.2020.35.e176
  59. World Health Organization. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 [Internet]. Geneva (Switzerland): World Health Organization; 2020 [cited 2020 Jun 10]. Available from: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescentswith-covid-19.
  60. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020;395:1607-8. https://doi.org/10.1016/s0140-6736(20)31094-1
  61. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr 2020;10:537-40. https://doi.org/10.1542/hpeds.2020-0123
  62. Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Med Mal Infect 2020;50:382-3. https://doi.org/10.1016/j.medmal.2020.04.002
  63. Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 2020;18:164. https://doi.org/10.1186/s12967-020-02339-3
  64. Balasubramanian S, Nagendran TM, Ramachandran B, Ramanan AV. Hyper-inflammatory syndrome in a child with COVID-19 treated successfully with intravenous immunoglobulin and tocilizumab. Indian Pediatr 2020;57:681-3. https://doi.org/10.1007/s13312-020-1901-z
  65. Odievre MH, de Marcellus C, Ducou Le Pointe H, Allali S, Romain AS, Youn J, et al. Dramatic improvement after tocilizumab of severe COVID-19 in a child with sickle cell disease and acute chest syndrome. Am J Hematol 2020;95:E192-4. https://doi.org/10.1002/ajh.25855
  66. National Health Commission & National Administration of Traditional Chinese Medicine. Diagnosis and treatment protocol for novel coronavirus pneumonia (trial version 7). Chin Med J (Engl) 2020;133:1087-95. https://doi.org/10.1097/CM9.0000000000000819
  67. Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care 2020;24:128. https://doi.org/10.1186/s13054-020-2836-4
  68. Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A 2020;117:9490-6. https://doi.org/10.1073/pnas.2004168117
  69. Balkhair AA. COVID-19 pandemic: a new chapter in the history of infectious diseases. Oman Med J 2020;35:e123. https://doi.org/10.5001/omj.2020.41
  70. ClinicalTrials.gov. Safety, reactogenicity, and immunogenicity of mRNA-1273 COVID-19 vaccine in adults aged 18 years and older [Internet]. Bethesda (MD): ClinicalTrials.gov; 2020 [cited 2020 Jun 10]. Available from: https://clinicaltrials.gov/.
  71. Wang F, Kream RM, Stefano GB. An evidence based perspective on mRNA-SARS-CoV-2 vaccine development. Med Sci Monit 2020;26:e924700.
  72. Mullard A. COVID-19 vaccine development pipeline gears up. Lancet 2020;395:1751-2. https://doi.org/10.1016/s0140-6736(20)31252-6
  73. Callaway E. Coronavirus vaccine trials have delivered their first results - but their promise is still unclear. Nature 2020;581:363-4. https://doi.org/10.1038/d41586-020-01092-3
  74. Micallef J, Soeiro T, Jonville-Bera AP. Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection. Therapie 2020 May 7 [Epub]. https://doi.org/10.1016/j.therap.2020.05.003.
  75. Voiriot G, Philippot Q, Elabbadi A, Elbim C, Chalumeau M, Fartoukh M. Risks related to the use of non-steroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients. J Clin Med 2019;8:786. https://doi.org/10.3390/jcm8060786
  76. Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ 2020;368:m1185. https://doi.org/10.1136/bmj.m1185