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Therapeutics in the Treatment of COVID-19 for Children and Adolescents

소아청소년 코로나바이러스감염증-19의 치료: 치료 약제를 중심으로

  • Choi, Soo-Han (Department of Pediatrics, Pusan National University Hospital) ;
  • Choi, Jae Hong (Department of Pediatrics, Jeju National University School of Medicine) ;
  • Yun, Ki Wook (Department of Pediatrics, Seoul National University College of Medicine)
  • 최수한 (부산대학교병원 소아청소년과) ;
  • 최재홍 (제주대학교병원 소아청소년과) ;
  • 윤기욱 (서울대학교병원 소아청소년과)
  • Received : 2022.02.04
  • Accepted : 2022.03.04
  • Published : 2022.04.25

Abstract

Coronavirus disease 2019 (COVID-19) presents as a mild-to-moderate respiratory illness in most children. However, a small proportion of children with COVID-19 develop severe or critical illnesses. Although pediatric clinical trials for the treatment of COVID-19 are sparse, some drugs are available for children and adolescents with severe COVID-19. This review summarizes clinical data focusing on antiviral agents and immunomodulators for use in treating COVID-19. In addition, current recommendations for therapeutics for children and adolescents with COVID-19 are discussed.

소아청소년에서 코로나바이러스감염증-19 (coronavirus disease 2019 [COVID-19])은 대부분 경증이며 특별한 치료없이 호전될 수 있다. 하지만 일부 소아청소년 COVID-19 환자에서는 중증 또는 위중증으로 진행할 수 있다. 소아청소년 COVID-19 치료 약제에 대한 임상 데이터는 제한적이지만, 중증 및 위중증 COVID-19 소아청소년 환자에서 사용 가능한 약제들은 있다. 본 종설에서는 COVID-19 치료 약제 중 항바이러스제와 면역조절제에 중점을 두고 임상 데이터와 소아청소년에 대한 권고 사항들을 논의하였다.

Keywords

Acknowledgement

We would like to thank Professor Yae-Jean Kim for her advice and consideration in creating this review.

References

  1. Fraile Navarro D, Tendal B, Tingay D, Vasilunas N, Anderson L, Best J, et al. Clinical care of children and adolescents with COVID-19: recommendations from the National COVID-19 Clinical Evidence Taskforce. Med J Aust 2021;mja2.51305.
  2. Lee H, Choi S, Park JY, Jo DS, Choi UY, Lee H, et al. Analysis of critical COVID-19 cases among children in Korea. J Korean Med Sci 2022;37:e13. https://doi.org/10.3346/jkms.2022.37.e13
  3. Woodruff RC, Campbell AP, Taylor CA, Chai SJ, Kawasaki B, Meek J, et al. Risk factors for severe COVID-19 in children. Pediatrics 2021;e2021053418.
  4. Kompaniyets L, Agathis NT, Nelson JM, Preston LE, Ko JY, Belay B, et al. Underlying medical conditions associated with severe COVID-19 illness among children. JAMA Netw Open 2021;4:e2111182. https://doi.org/10.1001/jamanetworkopen.2021.11182
  5. Chiotos K, Hayes M, Kimberlin DW, Jones SB, James SH, Pinninti SG, et al. Multicenter interim guidance on use of antivirals for children with coronavirus disease 2019/severe acute respiratory syndrome coronavirus 2. J Pediatric Infect Dis Soc 2021;10:34-48. https://doi.org/10.1093/jpids/piaa115
  6. Dulek DE, Fuhlbrigge RC, Tribble AC, Connelly JA, Loi MM, El Chebib H, et al. Multidisciplinary guidance regarding the use of immunomodulatory therapies for acute coronavirus disease 2019 in pediatric patients. J Pediatric Infect Dis Soc 2020;9:716-37. https://doi.org/10.1093/jpids/piaa098
  7. National Institute for Health and Care Excellence (NICE). COVID-19 rapid guideline: managing COVID-19 [Internet]. London: NICE; 2021 [cited 2022 Feb 27]. Available from: https://www.nice.org.uk/guidance/ng191/chapter/Recommendations
  8. National Institutes of Health (NIH). Coronavirus disease 2019 (COVID-19) treatment guidelines [Internet]. Bethesda: NIH; 2022 [cited 2022 Jan 24]. Available from: https://www.covid19treatmentguidelines.nih.gov/therapies/.
  9. World Health Organization (WHO). Therapeutics and COVID-19: living guideline [Internet]. Geneva: WHO; 2022 [cited 2022 Jan 21]. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.3.
  10. Infectious Diseases Society of America (IDSA). IDSA guidelines on the treatment and management of patients with COVID-19 [Internet]. Arlington: IDSA; 2022 [cited 2022 Jan 21]. Available from: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/.
  11. Hall MD, Anderson JM, Anderson A, Baker D, Bradner J, Brimacombe KR, et al. Report of the National Institutes of Health SARS-CoV-2 antiviral therapeutics summit. J Infect Dis 2021;224:S1-21. https://doi.org/10.1093/infdis/jiab305
  12. WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al. Repurposed antiviral drugs for COVID-19 - Interim WHO Solidarity Trial results. N Engl J Med 2021;384:497-511. https://doi.org/10.1056/NEJMoa2023184
  13. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of COVID-19 - final report. N Engl J Med 2020;383:1813-26. https://doi.org/10.1056/NEJMoa2007764
  14. Spinner CD, Gottlieb RL, Criner GJ, Arribas Lopez JR, Cattelan AM, Soriano Viladomiu A, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA 2020;324:1048-57. https://doi.org/10.1001/jama.2020.16349
  15. Goldman JD, Lye DC, Hui DS, Marks KM, Bruno R, Montejano R, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med 2020;383:1827-37. https://doi.org/10.1056/NEJMoa2015301
  16. Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. Early remdesivir to prevent progression to severe COVID-19 in outpatients. N Engl J Med 2022;386:305-15. https://doi.org/10.1056/NEJMoa2116846
  17. Gilead Sciences. Study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of remdesivir (GS-5734TM) in participants from birth to < 18 years of age with coronavirus disease 2019 (COVID-19) (CARAVAN) [Internet]. Bethesda: National Institutes of Health (NIH); 2021 [cited 2022 Jan 14]. Available from: https://clinicaltrials.gov/ct2/show/NCT04431453?term=remdesivir&cond=COVID-19&age=0&draw=2&rank=1.
  18. Goldman DL, Aldrich ML, Hagmann SH, Bamford A, Camacho-Gonzalez A, Lapadula G, et al. Compassionate use of remdesivir in children with severe COVID-19. Pediatrics 2021;147:e2020047803. https://doi.org/10.1542/peds.2020-047803
  19. Mendez-Echevarria A, Perez-Martinez A, Gonzalez Del Valle L, Ara MF, Melendo S, Ruiz de Valbuena M, et al. Compassionate use of remdesivir in children with COVID-19. Eur J Pediatr 2021;180:1317-22. https://doi.org/10.1007/s00431-020-03876-1
  20. National COVID-19 Clinical Evidence Taskforce (AU). Australian guidelines for the clinical care of people with COVID-19 [Internet]. Melbourne: National COVID-19 Clinical Evidence Taskforce; 2022 [cited 2022 Jan 21]. Available from: https://covid19evidence.net.au/#living-guidelines.
  21. U.S. Food and Drug Administration (FDA). FDA takes actions to expand use of treatment for outpatients with mild-to-moderate COVID-19 [Internet]. Silver Spring: FDA; 2022 [cited 2022 Jan 24]. Available from: https://www.fda.gov/news-events/press-announcements/fda-takes-actions-expand-use-treatment-outpatients-mild-moderate-covid-19.
  22. National Institutes of Health (NIH). Coronavirus disease 2019 (COVID-19) treatment guidelines. Special considerations in children [Internet]. Bethesda: NIH; 2021 [cited 2022 Jan 14]. Available from: https://www.covid19treatmentguidelines.nih.gov/special-populations/children/.
  23. Korea Disease Control and Prevention Agency (KDCA). Guidance on the use of COVID-19 treatment [Internet]. Cheongju: KDCA; 2022 [cited 2022 Feb 27]. Available from: http://ncov.mohw.go.kr/shBoardView.do?brdId=2&brdGubun=24&ncvContSeq=5314.
  24. Korea Ministry of Food and Drug Safety (MFDS). Changes in the approval of remdesivir [Internet]. Cheongju: MFDS; 2022 [cited 2022 Jan 14]. Available from: https://www.mfds.go.kr/brd/m_99/view.do?seq=46060.
  25. Korea Ministry of Food and Drug Safety (MFDS). Approval for additional emergency use of remdesivir [Internet]. Cheongju: MFDS; 2022 [cited 2022 Jan 25]. Available from: https://www.mfds.go.kr/brd/m_99/view.do?seq=46086.
  26. U.S. Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization for paxlovid [Internet]. Silver Spring: FDA; 2021 [cited 2022 Jan 14]. Available from: https://www.fda.gov/media/155050/download.
  27. Pourkarim F, Pourtaghi-Anvarian S, Rezaee H. Molnupiravir: a new candidate for COVID-19 treatment. Pharmacol Res Perspect 2022;10:e00909.
  28. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. N Engl J Med 2022;386:509-20. https://doi.org/10.1056/NEJMoa2116044
  29. U.S. Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization for molnupiravir [Internet]. Silver Spring: FDA; 2021 [cited 2022 Jan 14]. Available from: https://www.fda.gov/media/155054/download.
  30. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4. https://doi.org/10.1016/s0140-6736(20)30628-0
  31. Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: the REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA 2020;324:1317-29. https://doi.org/10.1001/jama.2020.17022
  32. Dequin PF, Heming N, Meziani F, Plantefeve G, Voiriot G, Badie J, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: a randomized clinical trial. JAMA 2020;324:1298-306. https://doi.org/10.1001/jama.2020.16761
  33. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 2020;324:1330-41. https://doi.org/10.1001/jama.2020.17023
  34. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA 2020;324:1307-16. https://doi.org/10.1001/jama.2020.17021
  35. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 2021;384:693-704. https://doi.org/10.1056/NEJMoa2021436
  36. Jeronimo CM, Farias ME, Val FF, Sampaio VS, Alexandre MA, Melo GC, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with coronavirus disease 2019 (COVID-19; Metcovid): a randomized, double-blind, phase IIb, placebo-controlled trial. Clin Infect Dis 2021;72:e373-81. https://doi.org/10.1093/cid/ciaa1177
  37. U.S. Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization for Actemra (tocilizumab) [Internet]. Silver Spring: FDA; 2021 [cited 2022 Jan 21]. Available from: https://www.fda.gov/media/150321/download.
  38. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021;397:1637-45. https://doi.org/10.1016/S0140-6736(21)00676-0
  39. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JP, et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA 2021;326:499-518. https://doi.org/10.1001/jama.2021.11330
  40. Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med 2021;384:795-807. https://doi.org/10.1056/NEJMoa2031994
  41. Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med 2021;9:1407-18. https://doi.org/10.1016/S2213-2600(21)00331-3
  42. U.S. Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization of baricitinib [Internet]. Silver Spring: FDA; 2021 [cited 2022 Jan 21]. Available from: https://www.fda.gov/media/143823/download.
  43. Dougan M, Azizad M, Mocherla B, Gottlieb RL, Chen P, Hebert C, et al. A randomized, placebocontrolled clinical trial of bamlanivimab and etesevimab together in high-risk ambulatory patients with COVID-19 and validation of the prognostic value of persistently high viral load. Clin Infect Dis 2021;ciab912.
  44. Dougan M, Nirula A, Azizad M, Mocherla B, Gottlieb RL, Chen P, et al. Bamlanivimab plus etesevimab in mild or moderate COVID-19. N Engl J Med 2021;385:1382-92. https://doi.org/10.1056/NEJMoa2102685
  45. Gupta A, Gonzalez-Rojas Y, Juarez E, Crespo Casal M, Moya J, Falci DR, et al. Early treatment for COVID-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med 2021;385:1941-50. https://doi.org/10.1056/NEJMoa2107934
  46. Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, et al. REGEN-COV antibody combination and outcomes in outpatients with COVID-19. N Engl J Med 2021;385:e81. https://doi.org/10.1056/NEJMoa2108163
  47. Mak G, Dassner AM, Hammer BM, Hanisch BR. Safety and tolerability of monoclonal antibody therapies for treatment of COVID-19 in pediatric patients. Pediatr Infect Dis J 2021;40:e507-9. https://doi.org/10.1097/INF.0000000000003263
  48. American Academy of Pediatrics (AAP). Management of strategies in children and adolescents with mild to moderate COVID-19 [Internet]. Itasca: AAP; 2022 [cited 2022 Jan 25]. Available from: https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/outpatient-covid-19-management-strategies-in-children-and-adolescents/.
  49. U.S. Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization of bamlanivimab and etesevimab [Internet]. Silver Spring: FDA; 2021 [cited 2022 Jan 25]. Available from: https://www.fda.gov/media/145802/download.
  50. Cameroni E, Bowen JE, Rosen LE, Saliba C, Zepeda SK, Culap K, et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature 2022;602:664-70. https://doi.org/10.1038/s41586-021-04386-2
  51. U.S. Food and Drug Administration (FDA). Coronavirus (COVID-19) update: FDA limits use of certain monoclonal antibodies to treat COVID-19 due to the Omicron variant [Internet]. Silver Spring: FDA; 2022 [cited 2022 Jan 25]. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-limits-use-certain-monoclonal-antibodies-treat-covid-19-due-omicron.