A Systematic Review of Gastrointestinal Manifestations in Children Presenting with COVID-19

Authors

  • Silvia Salvatore Department of Pediatrics, Ospedale “F. Del Ponte”, University of Insubria, Varese, Italy
  • Massimo Agosti Department of Pediatrics, Ospedale “F. Del Ponte”, University of Insubria, Varese, Italy
  • Serena Arrigo Department of Pediatrics, Ospedale “F. Del Ponte”, University of Insubria, Varese, Italy
  • Marta Stracuzzi Department of Pediatrics, Ospedale dei Bambini, University of Milan, ASST FBF SACCO, Milan, Italy
  • Dario Dilillo Department of Pediatrics, Ospedale dei Bambini, University of Milan, ASST FBF SACCO, Milan, Italy
  • Laura Folgori Department of Pediatrics, Ospedale dei Bambini, University of Milan, ASST FBF SACCO, Milan, Italy
  • Roberta Giacchero Department of Pediatrics, Ospedale Maggiore di Lodi, Lodi, Italy
  • Vania Giacomet Department of Pediatrics, Ospedale dei Bambini, University of Milan, ASST FBF SACCO, Milan, Italy
  • Emma Longoni Department of Pediatrics, Ospedale dei Bambini, University of Milan, ASST FBF SACCO, Milan, Italy
  • Antonella Meini Department of Pediatrics, University of Brescia, Spedali Civili, Brescia, Italy
  • Gian Luigi Marseglia Department of Pediatrics IRCCS Policlinico San Matteo Foundation-University of Pavia
  • Alessandro Plebani Department of Pediatrics, University of Brescia, Spedali Civili, Brescia, Italy
  • Alessandro Ferdinando Ruffolo IRCCS San Raffaele Hospital, Università Vita-Salute San Raffaele, Milano
  • Lucia Barcellini Department of Pediatrics, Ospedale dei Bambini, University of Milan, ASST FBF SACCO, Milan, Italy
  • Gianvincenzo Zuccotti Department of Pediatrics, Ospedale dei Bambini, University of Milan, ASST FBF SACCO, Milan, Italy

DOI:

https://doi.org/10.12974/2311-8687.2021.09.1

Keywords:

SARS-CoV-2, COVID-19, Coronavirus, Gastrointestinal, Diarrhea, Vomit, Abdominal pain, Poor feeding, Children.

Abstract

SARS-CoV-2 infection commonly presents with mild to severe respiratory symptoms and possibly other organs involvement. Gastrointestinal manifestations have been frequently documented in adult patients whilst their occurrence in children is uncertain. This study aimed to perform a Systematic Review of gastrointestinal symptoms in children with Coronavirus disease (COVID-19) and to compare these clinical findings with those reported in a cohort of Italian children in the early phase of pandemic.

Methods: Literature search was conducted using the Cochrane Library and MEDLINE (via Pubmed) databases from 1st December 2019 to 28th April 2020, according to the PRISMA guidelines. The following search terms were inserted: “Coronavirus” OR “COVID-19” OR “SARS-CoV-2” AND “gastrointestinal” or “diarrhea”. Only papers including children (0-18 years) and gastrointestinal symptoms were considered as eligible. Data records of children living in Lombardy, Italy, with infection of SARS-CoV-2 diagnosed by rRT-PCR on pharyngeal swabs, from 1st March to 28th April were also collected, analyzed and compared.

Results: The Systematic Review showed that only a minority of studies assessed gastrointestinal symptoms in children. However, diarrhea accounted for 0-50%, vomit 5-67% and abdominal pain 5.8-33.3% of infected children and gastrointestinal symptoms may represent the sole feature of COVID-19. Gastrointestinal symptoms were reported in 51/116 (44%) Italian children with SARS-CoV-2 infection. Poor feeding was present in 23.3% of children, diarrhea (median duration 2.3 days, range 1-5 days) in 22.4%, vomit in 10.4% and abdominal pain in 6.9% of cases. Respiratory symptoms were reported in 35.3% of children with gastrointestinal symptoms that represented the first clinical manifestation of COVID-19 in 25% of all patients.

Conclusions: We found that gastrointestinal symptoms are common in children with COVID-19 and, in some cases, they may represent the first and the sole clinical manifestation of SARS-CoV-2 infection. Health care professionals must be aware of the frequent gastrointestinal involvement in children to assure an accurate diagnosis and therapeutic management. The correct identification of children with COVID-19 is also crucial to adopt preventive measures and to limit the transmission of the virus. 

References

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 DOI: https://doi.org/10.1056/NEJMoa2001017

Task force COVID-19 del Dipartimento Malattie Infettive e Servizio di Informatica, Istituto Superiore di Sanità. Epidemia COVID-19, Aggiornamento nazionale: 16 aprile 2020

[Online]. Available: https: //www.epicentro.iss.it/coronavirus/bollettino/Bollettinosorveglianza- integrata-COVID-19_16-aprile-2020.

Coronavirus disease 2019 (COVID-19) in the EU/EEA and the UK - ninth update, 23 April 2020. Stockholm: ECDC; 2020.

CDC COVID-19 Response Team. Coronavirus Disease 2019 in Children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep 2020; 69: 422-426. https://doi.org/10.15585/mmwr.mm6914e4 DOI: https://doi.org/10.15585/mmwr.mm6914e4

Guan WJ, Ni ZY, Hu YU, et al. Clinical characteristics of Coronavirus disease 2019 in China. N Engl J Med 2020; 382: 1708-1720. https://doi.org/10.1056/NEJMoa2002032 DOI: https://doi.org/10.1056/NEJMoa2002032

Redd WD, Zhou JC, Hathorn KE, McCarty TR, Bazarbashi AN, Thompson CC, Shen L, Chan WW. Prevalence and Characteristics of Gastrointestinal Symptoms in Patients with SARS-CoV-2 Infection in the United States: A Multicenter Cohort Stud. Gastroenterology. 2020; 159(2): 765-767.e2. https://doi.org/10.1053/j.gastro.2020.04.045 DOI: https://doi.org/10.1053/j.gastro.2020.04.045

Nobel YR, Phipps M, Zucker J, Lebwohl B, Wang TC, Sobieszczyk ME, Freedberg. Gastrointestinal Symptoms and COVID-19: Case-Control Study from the United States.. Gastroenterology. 2020; 159(1): 373-375.e2. https://doi.org/10.1053/j.gastro.2020.04.017 DOI: https://doi.org/10.1053/j.gastro.2020.04.017

Tian Y, Rong L, Nian W, He Y Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020; 51(9): 843-851. https://doi.org/10.1111/apt.15731 DOI: https://doi.org/10.1111/apt.15731

Hajifathalian K, Mahadev S, Schwartz RE, et al. SARS-COV- 2 infection (coronavirus disease 2019) for the gastrointestinal consultant. World J Gastroenterol. 2020; 26(14): 1546-1553. https://doi.org/10.3748/wjg.v26.i14.1546 DOI: https://doi.org/10.3748/wjg.v26.i14.1546

Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterology. 2020; 159(1): 81-95. https://doi.org/10.1053/j.gastro.2020.03.065 DOI: https://doi.org/10.1053/j.gastro.2020.03.065

Cai JH, Wang XS, Ge YL, et al. First case of 2019 novel coronavirus infection in children in Shanghai. Zhonghua Er Ke Za Zhi. 2020; 58(2): 86-87.

Chen F, Liu ZS, Zhang FR, et al. First case of severe childhood novel coronavirus pneumonia in China. Zhonghua Er Ke Za Zhi. 2020; 58(3): 179-182.

Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. First case of neonate infected with novel coronavirus pneumonia in China. Zhonghua Er Ke Za Zhi. 2020; 58(0): E009.

Pediatric Branch of Hubei Medical Association; Pediatric Branch of Wuhan Medical Association; Pediatric Medical Quality Control Center of Hubei.

[Recommendation for the diagnosis and treatment of novel coronavirus infection in children in Hubei (trial version 1)]. Zhongguo Dang Dai Er Ke Za Zhi. 2020; 22(2): 96-99

Chen ZM, Fu JF, Shu Q, et al. Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.

[published online February 25, 2020].World J Pediatr. 2020. https://doi.org/10.1007/s12519-020-00345-5 DOI: https://doi.org/10.1007/s12519-020-00345-5

Dong Y, Mo X, Hu Y. et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. March e20200702.

Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020. 158(6): 1831-1833.e3. https://doi.org/10.1053/j.gastro.2020.02.055 DOI: https://doi.org/10.1053/j.gastro.2020.02.055

Donà D, Minotti C, Costenaro P, Da Dalt L, Giaquinto C. Fecal-oral transmission of sars-cov-2 in children: is it time to change our approach? Pediatr Infect Dis J. 2020; 39(7): e133-e134. https://doi.org/10.1097/INF.0000000000002704 DOI: https://doi.org/10.1097/INF.0000000000002704

Yu-Han Xing, Wei Ni, Qin Wu, Wen-Jie Li, Guo-Ju Li, Wen-Di Wang. Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019. J. Microbiol Immunol Infect. Available online 28 March 2020. PMID: 32276848 DOI: https://doi.org/10.1016/j.jmii.2020.03.021

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 DOI: https://doi.org/10.1056/NEJMc2003717

Shen Q, Guo W, Guo T, Li J, He W, Ni S, Ouyang X, Liu J, Xie Y, Tan X, Zhou Z, Peng H. Novel coronavirus infection in children outside of Wuhan, China. Pediatr Pulmonol. 2020; 55(6): 1424-1429. https://doi.org/10.1002/ppul.24762 DOI: https://doi.org/10.1002/ppul.24762

Cai J, Xu J, Lin D, Yang Z, Xu L, Qu Z, Zhang Y, et al. A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis 2020; Feb 28

[Epub].

Xu Y, Li X, Zhu B. et al. Characteristics of pediatric SARSCoV- 2 infection and potential evidence for persistent fecal viral shedding. Nat Med 2020; 26: 502-505. https://doi.org/10.1038/s41591-020-0817-4 DOI: https://doi.org/10.1038/s41591-020-0817-4

Xia W, Shao J, Guo Y, Peng X, Li Z, Hu D. Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults. Pediatr Pulmonol 2020; Mar 5

[Epub]. https://doi.org/10.1002/ppul.24718 DOI: https://doi.org/10.1002/ppul.24718

Shen KL, Yang YH. Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue. World J Pediatr. Published online February 5, 2020. https://doi.org/10.1007/s12519-020-00344-6 DOI: https://doi.org/10.1007/s12519-020-00344-6

Wang D, Ju XL, Xie F, Lu Y, Li FY, Huang HH, et al. Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China. Zhonghua Er Ke Za Zhi 2020; 58: E011.

Tagarro A, Epalza C, Santos M, et al. Screening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain JAMA Pediatr. Published online April 8, 2020. https://doi.org/10.1001/jamapediatrics.2020.1346 DOI: https://doi.org/10.1001/jamapediatrics.2020.1346

Chang TH, Wu JL, Chang LY. Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis. J Formos Med Assoc. 2020; 119(5): 982-989. https://doi.org/10.1016/j.jfma.2020.04.007 DOI: https://doi.org/10.1016/j.jfma.2020.04.007

Lu X, Zhang L, Du H, et al. SARS‐CoV‐2 infection in children. N Engl J Med. 2020; 23; 382(17): 1663-1665. DOI: https://doi.org/10.1056/NEJMc2005073

Henry BM, de Oliveira MHS, Benoit J, Lippi G. Gatrointestinal symptoms associated with severity of coronavirus disease 2019 (COVID-19): a pooled analysis. Intern Emerg Med. 2020; 15(5): 857-859. https://doi.org/10.1007/s11739-020-02329-9 DOI: https://doi.org/10.1007/s11739-020-02329-9

Yang X, Yu Y, Xu J. et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Resp Med.2020. Published online Feb 24. https://doi.org/10.1016/S2213-2600(20)30079-5 DOI: https://doi.org/10.1016/S2213-2600(20)30079-5

Lin L, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut 69(6): 997-1001. https://doi.org/10.1136/gutjnl-2020-321013 DOI: https://doi.org/10.1136/gutjnl-2020-321013

Zhang H, Kang Z, Gong H, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. BioRxiv 2020. https://doi.org/10.1101/2020.01.30.927806 DOI: https://doi.org/10.1101/2020.01.30.927806

Gralnek IM, Hassan C, Beilenhoff U, et al. ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemic. Endoscopy. 2020; 52(6): 483- 490. https://doi.org/10.1055/a-1155-6229 DOI: https://doi.org/10.1055/a-1155-6229

Walsh CM, Fishman DS, Lerner DG; NASPGHAN Endoscopy and Procedures Committee. Pediatric Endoscopy in the Era of Coronavirus Disease 2019: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper. J Pediatr Gastroenterol Nutr. 2020; 70(6): 741-750. https://doi.org/10.1097/MPG.0000000000002750 DOI: https://doi.org/10.1097/MPG.0000000000002750

Norsa L, Indriolo A, Sansotta N. et al. Uneventful course in IBD patients during SARS-CoV-2 outbreak in northern Italy. Gastroenterology 2020; 159(1): 371-372. https://doi.org/10.1053/j.gastro.2020.03.062 DOI: https://doi.org/10.1053/j.gastro.2020.03.062

D'Antiga L. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver Transpl, 2020; 26(6): 832-834. https://doi.org/10.1002/lt.25756 DOI: https://doi.org/10.1002/lt.25756

Turner D, Huang Y, Martín-de-Carpi J, et al. COVID-19 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto group of ESPGHAN. J Pediatr Gastroenterol Nutr. 2020; 70(6): 727-733. https://doi.org/10.1097/MPG.0000000000002729 DOI: https://doi.org/10.1097/MPG.0000000000002729

Downloads

Published

2021-06-02

How to Cite

Salvatore, S., Agosti, M., Arrigo, S., Stracuzzi, M., Dilillo, D., Folgori, L., Giacchero, R., Giacomet, V., Longoni, E., Meini, A., Marseglia, G. L., Plebani, A., Ruffolo, A. F., Barcellini, L., & Zuccotti, G. (2021). A Systematic Review of Gastrointestinal Manifestations in Children Presenting with COVID-19. International Journal of Pediatrics and Child Health, 9, 1–11. https://doi.org/10.12974/2311-8687.2021.09.1

Issue

Vol. 9 (2021)

Section

Articles