Comorbidities and COVID-19 severity in pediatric patients: systematic review and meta-analysis

  • Mas Wishnuwardhana Widjanarko Pediatric Division, Chasbullah Abdulmadjid Hospital, Bekasi West Java
  • Mutiara Nindya Pediatric Division, Chasbullah Abdulmadjid Hospital, Bekasi West Java
  • Glenn Fernandez Pediatric Division, Chasbullah Abdulmadjid Hospital, Bekasi West Java
  • Axel Jovito Pediatric Division, Chasbullah Abdulmadjid Hospital, Bekasi West Java
Keywords: children; COVID-19; novel coronavirus; SARS-CoV-2

Abstract

Background COVID-19 has spread around the world. Although symptoms in children are often mild, children remain at risk of developing severe or critical forms of COVID-19, especially those with underlying or comorbid medical conditions.

Objective To evaluate the association between comorbidities and severity of COVID-19 in pediatric patients.

Methods A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We used PubMed and Google Scholar to locate observational studies that involved children with RT-PCR-confirmed COVID-19 with comorbidities and compared them with controls without comorbidities. Studies must also involve children with severe COVID-19 and provide the risk of severe COVID-19 in children with and without comorbidities as outcome. We performed a meta-analysis to estimate the pooled odds ratio (OR) of severe COVID-19 in children with vs. without comorbidities.

Results We included 41 observational studies with a total of 285,828 pediatric COVID-19 patients, comprising 9,754 patients with comorbidities and 276,074 controls. The comorbidities indentified included obesity, congenital malformations, neurological disease, and genetic syndromes. Children with comorbidities had a significantly higher risk of developing severe COVID-19 compared to those without (pooled OR 4.07; 95%CI 2.31 to 7.19; P<0.00001).

Conclusion The presence of comorbidities increases the risk of severe COVID-19 in children.

References

1. Wu YC, Chen CS, Chan YJ. The outbreak of COVID-19: an overview. J Chin Med Assoc. 2020;83:217-20. DOI: 10.1097/JCMA.0000000000000270.
2. World Health Organization (WHO). Coronavirus disease (COVID-19) pandemic [internet]. 2021 [cited 2021 May 3]. Available from: https://www.who.int/covid-19.
3. Susanna D. When will the COVID-19 Pandemic in Indonesia end? J Kesehatan Masyarakat Nasional (National Public Health Journal). 2020;15:160-2. DOI: 10.21109/kesmas.v15i4.4361.
4. Ritchie H, Ospina EO, Beltekian D, Mathieu E, Hasell J, Macdonald B, et al. Coronavirus pandemic (COVID-19) – the data. 2021. [Updated 2021 May 3]; [cited 2021 May 3]. Available from: https://ourworldindata.org/coronavirus-data
5. Mirza A. Coronavirus Disease 2019 (COVID-19) in Children. [internet]. [cited 2021 May 3]. Available from: https://emedicine.medscape.com/article/2500132-overview#a6.
6. Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020;92:568-76. DOI: 10.1002/jmv.25748.
7. 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. DOI: 10.1007/s12519-020-00343-7.
8. Mannheim J, Gretsch S, Layden JE, Fricchione MJ. Characteristics of hospitalized pediatric coronavirus disease 2019 cases in Chicago, Illinois, March–April 2020. J Pediatric Infect Dis Soc. 2020;9:519-22. DOI: 10.1093/jpids/piaa070.
9. Cruz AT, Zeichner SL. COVID-19 in children: initial characterization of the pediatric disease. Pediatrics. 2020;145:e20200834. DOI: 10.1542/peds.2020-0834.e20200834.
10. Abdel-Mannan O, Eyre M, Löbel U, Bamford A, Eltze C, Hameed B, et al. Neurologic and radiographic findings associated with COVID-19 infection in children. JAMA Neurol. 2020;77:1440-5. DOI: 10.1001/jamaneurol.2020.2687.
11. STROBE. STROBE checklist [internet]. 2021 [cited 2021 may 3]. Available from: https://www.strobe-statement.org/checklists/.
12. The Joanna Briggs Institute (JBI). The Joanna Briggs Institute (JBI) critical appraisal checklist for case series studies. 2021 [cited 2021 may 3]. Available from: https://jbi.global/critical-appraisal-tools.
13. Alfaraij A, Alamir A, Al-Otaibi AM, Alsharrah B, Aldaithan A, Kamel AM, et al. Characteristics and outcomes of coronavirus disease 2019 (COVID-19) in critically ill pediatric patients admitted to the intensive care unit: a multicenter retrospective cohort study. J Infect Public Health. 2021;14:193-200. DOI: 10.1016/j.jiph.2020.12.010.
14. Anand P, Yadav A, Debata P, Bachani S, Gupta N, Gera R. Clinical profile, viral load, management and outcome of neonates born to COVID 19 positive mothers: a tertiary care centre experience from India. Eur J Pediatr. 2020;180:547-59. DOI: 10.1007/s00431-020-03800-7.
15. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation. 2020;142:429-36. DOI: 10.1161/CIRCULATIONAHA.120.048360.
16. Bellino S, Punzo O, Rota MC, Del Manso M, Urdiales AM, Andrianou X, et al. COVID-19 disease severity risk factors for pediatric patients in Italy. Pediatrics. 2020;146:e2020009399. DOI: 10.1542/peds.2020-009399.
17. Bhumbra S, Malin S, Kirkpatrick L, Khaitan A, John CC, Rowan CM, et al. Clinical features of critical coronavirus disease 2019 in children. Pediatr Crit Care Med. 2020;21:e948-53. DOI: 10.1097/PCC.0000000000002511.
18. Biko DM, Ramirez-Suarez KI, Barrera CA, Banerjee A, Matsubara D, Kaplan SL, et al. Imaging of children with COVID-19: experience from a tertiary children’s hospital in the United States. Pediatr Radiol. 2021;51:239-47. DOI: 10.1007/s00247-020-04830-x.
19. Blumfield E, Levin TL. COVID-19 in pediatric patients: a case series from the Bronx, NY. Pediatr Radiol. 2020;50:1369–74. DOI: 10.1007/s00247-020-04782-2.
20. Cai X, Ma Y, Li S, Chen Y, Rong Z, Li W. Clinical characteristics of 5 COVID-19 cases with non-respiratory symptoms as the first manifestation in children. Front Pediatr. 2020;8:258. DOI: 10.3389/fped.2020.00258.
21. Chao JY, Derespina KR, Herold BC, Goldman DL, Aldrich M, Weingarten J, et al. Clinical characteristics and outcomes of hospitalized and critically ill children and adolescents with coronavirus disease 2019 at a tertiary care medical center in New York City. J Pediatr. 2020;223:14-9.e2. DOI: 10.1016/j.jpeds.2020.05.006.
22. DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe coronavirus disease-2019 in children and young adults in the Washington, DC, metropolitan region. J Pediatr. 2020;223:199-203.e1. DOI: 10.1016/j.jpeds.2020.05.007.
23. de Farias ECF, Pedro Piva J, de Mello MLFMF, do Nascimento LMPP, Costa CC, Machado MMM, et al. Multisystem inflammatory syndrome associated with coronavirus disease in children: a multi-centered study in Belém, Pará, Brazil. Pediatr Infect Dis J. 2020;39:e374-6. DOI: 10.1097/INF.0000000000002865.
24. Derespina KR, Kaushik S, Plichta A, Conway EE, Bercow A, Choi J, et al. Clinical manifestations and outcomes of critically ill children and adolescents with coronavirus disease 2019 in New York City. J Pediatr. 2020;226:55-63.e2. DOI: 10.1016/j.jpeds.2020.07.039.
25. Diorio C, Henrickson SE, Vella LA, McNerney KO, Chase J, Burudpakdee C, et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2. J Clin Invest. 2020;130:5967–75. DOI: 10.1172/JCI140970.
26. Du H, Dong X, Zhang J, Cao Y, Akdis M, Huang P, et al. Clinical characteristics of 182 pediatric COVID? 19 patients with different severities and allergic status. Allergy. 2021;76:510-32. DOI: 10.1111/all.14452.
27. Eghbali A, Shokrollahi S, Mahdavi NS, Mahdavi SA, Dabbagh A. COVID-19 in pediatric patients: a case series. J Cell Mol Anesth. 2020;5:3–5. DOI: 10.22037/jcma.v5i1.29690.
28. Garazzino S, Montagnani C, Donà D, Meini A, Felici E, Vergine G, et al. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020. Eurosurveill. 2020;25:2000600. DOI: 10.2807/1560-7917.ES.2020.25.18.2000600.
29. García-Salido A, Leoz-Gordillo I, Martínez de Azagra-Garde A, Nieto-Moro M, Iglesias-Bouzas MI, García-Teresa MÁ, 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;21:e576–80. DOI: 10.1097/PCC.0000000000002475.
30. Giacomet V, Barcellini L, Stracuzzi M, Longoni E, Folgori L, Leone A, et al. Gastrointestinal symptoms in severe COVID-19 children. Pediatr Infect Dis J. 2020;39:e317-20. DOI: 10.1097/INF.0000000000002843.
31. González-Dambrauskas S, Vásquez-Hoyos P, Camporesi A, Díaz-Rubio F, Piñeres-Olave BE, Fernández-Sarmiento J, et al. Pediatric critical care and COVID-19. Pediatrics. 2020;146:e20201766. DOI: 10.1542/peds.2020-1766.
32. Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Calò Carducci FI, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health. 2020;4:653-61. DOI: 10.1016/S2352-4642(20)30177-2.
33. Fisler G, Izard SM, Shah S, Lewis D, Kainth MK, Hagmann SHF, et al. Characteristics and risk factors associated with critical illness in pediatric COVID-19. Ann Intensive Care. 2020;10:171. DOI: 10.1186/s13613-020-00790-5.
34. Kainth MK, Goenka PK, Williamson KA, Fishbein JS, Subramony A, Barone S, et al. Early experience of COVID-19 in a US children’s hospital. Pediatrics. 2020;146:e2020003186. DOI: 10.1542/peds.2020-003186.
35. Kaushik S, Aydin SI, Derespina KR, Bansal PB, Kowalsky S, Trachtman R, et al. Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 Infection (MIS-C): a multi-institutional study from New York City. J Pediatr. 2020;224:24–9. DOI: 10.1016/j.jpeds.2020.06.045.
36. Kanthimathinathan HK, Dhesi A, Hartshorn S, Ali SH, Kirk J, Nagakumar P, et al. COVID-19: a UK children's hospital experience. Hosp Pediatr. 2020;10:802-5. DOI: 10.1542/hpeds.2020-000208.
37. Ibrahim LF, Tosif S, McNab S, Hall S, Lee HJ, Lewana S, et al. SARS-CoV-2 testing and outcomes in the first 30 days after the first case of COVID-19 at an Australian children’s hospital. Emerg Med Australas. 2020;32:801-8. DOI: 10.1111/1742-6723.13550.
38. Leeb RT, Price S, Sliwa S, Kimball A, Szucs L, Caruso E, et al. COVID-19 trends among school-aged children — United States, March 1–September 19, 2020. MMWR Morb Mortal Wkly Rep. 2020;69;1410–5. DOI: 10.15585/mmwr.mm6939e2.
39. Lovinsky-Desir S, Deshpande DR, De A, Murray L, Stingone JA, Chan A, et al. Asthma among hospitalized patients with COVID-19 and related outcomes. J Allergy Clin Immunol. 2020; 146:1027-34. DOI: 10.1016/j.jaci.2020.07.026.
40. Meslin P, Guiomard C, Chouakria M, Porcher J, Duquesne F, Tiprez C, et al. Coronavirus Disease 2019 in newborns and very young infants: a series of six patients in France. Pediatr Infect Dis J. 2020;39:e145-7. DOI: 10.1097/INF.0000000000002743.
41. Moreno-Galarraga L, Urretavizcaya-Martínez M, Alegría Echauri J, García Howard M, Ruperez García E, Aguilera-Albesa S, et al. SARS-CoV-2 infection in children requiring hospitalization: the experience of Navarra, Spain. World J Pediatr. 2020;16:614-22. DOI: 10.1007/s12519- 020-00393-x.
42. Oualha M, Bendavid M, Berteloot L, Corsia A, Lesage F, Vedrenne M, et al. Severe and fatal forms of COVID-19 in children. Arch Pediatr. 2020;27:235–8. DOI: 10.1016/j.arcped.2020.05.010.
43. Parri N, Lenge M, Cantoni B, Arrighini A, Romanengo M, Urbino A, et al. COVID-19 in 17 Italian Pediatric Emergency Departments. Pediatrics. 2020;146:e20201235. DOI: 10.1542/peds.2020-1235.
44. Riollano?Cruz M, Akkoyun E, Briceno?Brito E, Kowalsky S, Reed J, Posada R, et al. Multisystem inflammatory syndrome in children related to COVID? 19: a New York City experience. J Med Virol. 2021; 93:424-33. DOI: 10.1002/jmv.26224
45. Schwartz DA, Mohagheghi P, Beigi B, Zafaranloo N, Moshfegh F, Yazdani A. Spectrum of neonatal COVID-19 in Iran: 19 infants with SARS-CoV-2 perinatal infections with varying test results, clinical findings and outcomes. J Matern Fetal Neonatal. 2020:1-10. DOI: 10.1080/14767058.2020.1797672.
46. 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;174:868-73. DOI: 10.1001/jamapediatrics.2020.1948.
47. Swann OV, Holden KA, Turtle L, Pollock L, Fairfield CJ, Drake TM, et al. Clinical characteristics of children and young people admitted to hospital with COVID-19 in United Kingdom: prospective multicentre observational cohort study. BMJ. 2020;370:m3249. DOI: 10.1136/bmj.m3249.
48. Tagarro A, Epalza C, Santos M, Sanz-Santaeufemia FJ, Otheo E, Moraleda C, et al. Screening and severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain. JAMA Pediatr. 2020;8:e201346. DOI: 10.1001/jamapediatrics.2020.1346.
49. Yayla BCC, Yayla BCC, Özsürekçi Y, Aykaç K, Oygar PD, Gürlevik SL, ?lbay S, et al. Characteristics and management of children with COVID-19 in Turkey. Balkan Med J. 2020;37:341-7. DOI: 10.4274/balkanmedj.galenos.2020.2020.7.52.
50. Zachariah P, Johnson CL, Halabi KC, Ahn D, Sen AI, Fischer A, et al. Epidemiology, clinical features, and disease severity in patients with Coronavirus Disease 2019 (COVID-19) in a Children’s Hospital in New York City, New York. JAMA Pediatr. 2020;174:e202430. DOI: 10.1001/jamapediatrics.2020.2430.
51. Zheng F, Liao C, Fan Q, Chen H, Zhao X, Xie Z, et al. Clinical characteristics of children with Coronavirus Disease 2019 in Hubei, China. Curr Med Sci. 2020;40:275-80. DOI: 10.1007/s11596-020-2172-6.
52. 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. DOI: 10.1097/INF.0000000000002660.
53. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA Pediatr. 2020;324:782-93. DOI: 10.1001/jama.2020.12839.
54. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo?EM structure of the 2019?nCoV spike in the prefusion conformation. Science. 2020;367:1260-3. DOI: 10.1126/science.abb2507.
55. Simon AK, Hollander GA, McMichael A. Evolution of the immune system in humans from infancy to old age. Proc Biol Sci. 2015;22:20143085. DOI: 10.1098/rspb.2014.3085.
56. Badal S, Thapa Bajgain K, Badal S, Thapa R, Bajgain B, Santana M. Prevalence, clinical characteristics, and outcomes of pediatric COVID-19: a systematic review and meta-analysis. J Clin Virol. 2021;135:104715. DOI: 10.1016/j.jcv.2020.104715.
57. Cui X, Zhao Z, Zhang T, Guo W, Guo W, Zheng J, et al. A systematic review and meta?analysis of children with coronavirus disease 2019 (COVID?19). J Med Virol. 2020;93:1057-69. DOI: 10.1002/jmv.26398.
58. Mansourian M, Ghandi Y, Habibi D, Mehrabi S. COVID-19 infection in children: A systematic review and meta-analysis of clinical features and laboratory findings. Arch Pediatr. 2021;28:242-8. DOI: 10.1016/j.arcped.2020.12.008.
Published
2022-02-18
How to Cite
1.
Widjanarko M, Nindya M, Fernandez G, Jovito A. Comorbidities and COVID-19 severity in pediatric patients: systematic review and meta-analysis. PI [Internet]. 18Feb.2022 [cited 10Nov.2024];62(1):51-0. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2720
Section
Articles
Received 2021-07-12
Accepted 2022-02-18
Published 2022-02-18