Paediatric gastrointestinal disorders in SARS-CoV-2 infection: Epidemiological and clinical implications

Mohammed Al-Beltagi, Nermin Kamal Saeed, Adel Salah Bediwy, Yasser El-Sawaf, Mohammed Al-Beltagi, Nermin Kamal Saeed, Adel Salah Bediwy, Yasser El-Sawaf

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is a threat worldwide for individuals of all ages, including children. Gastrointestinal manifestations could be the initial presenting manifestation in many patients, especially in children. These symptoms are more common in patients with severe disease than in patients with non-severe disease. Approximately 48.1% of patients had a stool sample that was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA. Children typically form 1%-8% of all laboratory-confirmed cases of SARS-CoV-2. Gastrointestinal manifestations of COVID-19 in children are not rare, with a prevalence between 0 and 88%, and a wide variety of presentations, including diarrhoea, vomiting, and abdominal pain, can develop before, with or after the development of respiratory symptoms. Atypical manifestations such as appendicitis or liver injury could also appear, especially in the presence of multisystem inflammatory disease. In this review, we discussed the epidemiology of COVID-19 gastrointestinal diseases in children as well as their implications on the diagnosis, misdiagnosis, prognosis, and faecal-oral transmission route of COVID-19 and the impact of gastrointestinal diseases on the gut microbiome, child nutrition, and disease management.

Keywords: COVID-19; Children; Dysbiosis; Faecal-oral transmission; Gastrointestinal diseases; SARS-CoV-2.

Conflict of interest statement

Conflict-of-interest statement: The authors declare no conflicts of interest for this article.

©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Figures

Figure 1
Figure 1
Pathogenesis of gastrointestinal infection in coronavirus disease 2019. ACE2: Angiotensin-converting enzyme 2; IFN: Interferon; IgA: Immunoglobulin A; ROS: Reactive oxygen species.

References

    1. Hong KH, Lee SW, Kim TS, Huh HJ, Lee J, Kim SY, Park JS, Kim GJ, Sung H, Roh KH, Kim JS, Kim HS, Lee ST, Seong MW, Ryoo N, Lee H, Kwon KC, Yoo CK. Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea. Ann Lab Med. 2020;40:351–360.
    1. Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS, Dhama K, Yatoo MI, Bonilla-Aldana DK, Rodriguez-Morales AJ. SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview. Infez Med. 2020;28:174–184.
    1. Molloy EJ, Lavizzari A, Klingenberg C, Profit J, Zupancic JAF, Davis AS, Mosca F, Bearer CF, Roehr CC International Neonatal COVID-19 Consortium. Neonates in the COVID-19 pandemic. Pediatr Res. 2020
    1. Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Calò Carducci FI, Gabrovska N, Velizarova S, Prunk P, Osterman V, Krivec U, Lo Vecchio A, Shingadia D, Soriano-Arandes A, Melendo S, Lanari M, Pierantoni L, Wagner N, L'Huillier AG, Heininger U, Ritz N, Bandi S, Krajcar N, Roglić S, Santos M, Christiaens C, Creuven M, Buonsenso D, Welch SB, Bogyi M, Brinkmann F, Tebruegge M ptbnet COVID-19 Study Group. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health. 2020;4:653–661.
    1. Tai DBG, Shah A, Doubeni CA, Sia IG, Wieland ML. The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States. Clin Infect Dis. 2021;72:703–706.
    1. Zare-Zardini H, Soltaninejad H, Ferdosian F, Hamidieh AA, Memarpoor-Yazdi M. Coronavirus Disease 2019 (COVID-19) in Children: Prevalence, Diagnosis, Clinical Symptoms, and Treatment. Int J Gen Med. 2020;13:477–482.
    1. Lee PI, Hu YL, Chen PY, Huang YC, Hsueh PR. Are children less susceptible to COVID-19? J Microbiol Immunol Infect. 2020;53:371–372.
    1. Cristiani L, Mancino E, Matera L, Nenna R, Pierangeli A, Scagnolari C, Midulla F. Will children reveal their secret? Eur Respir J. 2020;55
    1. Nickbakhsh S, Mair C, Matthews L, Reeve R, Johnson PCD, Thorburn F, von Wissmann B, Reynolds A, McMenamin J, Gunson RN, Murcia PR. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proc Natl Acad Sci USA. 2019
    1. Skarstein Kolberg E. ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease. J Clin Virol. 2020;126:104350.
    1. Covián C, Fernández-Fierro A, Retamal-Díaz A, Díaz FE, Vasquez AE, Lay MK, Riedel CA, González PA, Bueno SM, Kalergis AM. BCG-Induced Cross-Protection and Development of Trained Immunity: Implication for Vaccine Design. Front Immunol. 2019;10:2806.
    1. Aguila EJT, Cua IHY, Dumagpi JEL, Francisco CPD, Raymundo NTV, Sy-Janairo MLL, Cabral-Prodigalidad PAI, Lontok MAD. COVID-19 and its effects on the digestive system and endoscopy practice. JGH Open. 2020;4:324–331.
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382:1708–1720.
    1. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, Wang HY, Zhang S, Gao HN, Sheng JF, Cai HL, Qiu YQ, Li LJ. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;368:m606.
    1. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020;323:1488–1494.
    1. Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R, Ng YY, Chu MY, Chung TWH, Tam AR, Yip CCY, Leung KH, Fung AY, Zhang RR, Lin Y, Cheng HM, Zhang AJX, To KKW, Chan KH, Yuen KY, Leung WK. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. Gastroenterology. 2020;159:81–95.
    1. Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, Hao SR, Jia HY, Cai H, Zhang XL, Yu GD, Xu KJ, Wang XY, Gu JQ, Zhang SY, Ye CY, Jin CL, Lu YF, Yu X, Yu XP, Huang JR, Xu KL, Ni Q, Yu CB, Zhu B, Li YT, Liu J, Zhao H, Zhang X, Yu L, Guo YZ, Su JW, Tao JJ, Lang GJ, Wu XX, Wu WR, Qv TT, Xiang DR, Yi P, Shi D, Chen Y, Ren Y, Qiu YQ, Li LJ, Sheng J, Yang Y. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020;69:1002–1009.
    1. Carvalho A, Alqusairi R, Adams A, Paul M, Kothari N, Peters S, DeBenedet AT. SARS-CoV-2 Gastrointestinal Infection Causing Hemorrhagic Colitis: Implications for Detection and Transmission of COVID-19 Disease. Am J Gastroenterol. 2020;115:942–946.
    1. Tullie L, Ford K, Bisharat M, Watson T, Thakkar H, Mullassery D, Giuliani S, Blackburn S, Cross K, De Coppi P, Curry J. Gastrointestinal features in children with COVID-19: an observation of varied presentation in eight children. Lancet Child Adolesc Health. 2020;4:e19–e20.
    1. Miller J, Cantor A, Zachariah P, Ahn D, Martinez M, Margolis KG. Gastrointestinal Symptoms as a Major Presentation Component of a Novel Multisystem Inflammatory Syndrome in Children That Is Related to Coronavirus Disease 2019: A Single Center Experience of 44 Cases. Gastroenterology 2020; 159: 1571-1574. :e2.
    1. Akobeng AK, Grafton-Clarke C, Abdelgadir I, Twum-Barimah E, Gordon M. Gastrointestinal manifestations of COVID-19 in children: a systematic review and meta-analysis. Front Gastroenterol . 2020;8
    1. Mayor S. Covid-19: UK studies find gastrointestinal symptoms are common in children. BMJ. 2020;370:m3484.
    1. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong GWK Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 Infection in Children. N Engl J Med. 2020;382:1663–1665.
    1. Cheng PK, Wong DA, Tong LK, Ip SM, Lo AC, Lau CS, Yeung EY, Lim WW. Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome. Lancet. 2004;363:1699–1700.
    1. Ojetti V, Saviano A, Covino M, Acampora N, Troiani E, Franceschi F GEMELLI AGAINST COVID‐19 group. COVID-19 and intestinal inflammation: Role of fecal calprotectin. Dig Liver Dis. 2020;52:1231–1233.
    1. Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V, Hanada T, Hanada R, Lipinski S, Wild B, Camargo SM, Singer D, Richter A, Kuba K, Fukamizu A, Schreiber S, Clevers H, Verrey F, Rosenstiel P, Penninger JM. ACE2 Links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012;487:477–481.
    1. Kim S, Rigatto K, Gazzana MB, Knorst MM, Richards EM, Pepine CJ, Raizada MK. Altered Gut Microbiome Profile in Patients With Pulmonary Arterial Hypertension. Hypertension. 2020;75:1063–1071.
    1. Villapol S. Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome. Transl Res. 2020;226:57–69.
    1. Stenstad H, Ericsson A, Johansson-Lindbom B, Svensson M, Marsal J, Mack M, Picarella D, Soler D, Marquez G, Briskin M, Agace WW. Gut-associated lymphoid tissue-primed CD4+ T cells display CCR9-dependent and -independent homing to the small intestine. Blood. 2006;107:3447–3454.
    1. Zhang D, Li S, Wang N, Tan HY, Zhang Z, Feng Y. The Cross-Talk Between Gut Microbiota and Lungs in Common Lung Diseases. Front Microbiol. 2020;11:301.
    1. Tripathi A, Debelius J, Brenner DA, Karin M, Loomba R, Schnabl B, Knight R. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018;15:397–411.
    1. Giacomet V, Barcellini L, Stracuzzi M, Longoni E, Folgori L, Leone A, Zuccotti GV COVID-19 Pediatric network. Gastrointestinal Symptoms in Severe COVID-19 Children. Pediatr Infect Dis J. 2020;39:e317–e320.
    1. Wang JG, Cui HR, Tang HB, Deng XL. Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis. Sci Rep. 2020;10:17846.
    1. Han C, Duan C, Zhang S, Spiegel B, Shi H, Wang W, Zhang L, Lin R, Liu J, Ding Z, Hou X. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Am J Gastroenterol. 2020;115:916–923.
    1. European Centre for Disease Prevention and Control. Options for the use of rapid antigen tests for COVID-19 in the EU/EEA and the UK. 19 November 2020. Stockholm: ECDC; 2020. [cited 2 December 2020]. Available from: .
    1. Scohy A, Anantharajah A, Bodéus M, Kabamba-Mukadi B, Verroken A, Rodriguez-Villalobos H. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J Clin Virol. 2020;129:104455.
    1. Huang I, Pranata R, Lim MA, Oehadian A, Alisjahbana B. C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Ther Adv Respir Dis. 2020;14:1753466620937175.
    1. Balasubramanian S, Rao NM, Goenka A, Roderick M, Ramanan AV. Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not. Indian Pediatr. 2020;57:435–442.
    1. Cipriano M, Ruberti E, Giacalone A. Gastrointestinal Infection Could Be New Focus for Coronavirus Diagnosis. Cureus. 2020;12:e7422.
    1. Altamimi E. Effect of COVID-19 Pandemic and Lockdown on Children With Gastrointestinal Disorders. Gastroenterology Res. 2020;13:125–128.
    1. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, Tamin A, Harcourt JL, Thornburg NJ, Gerber SI, Lloyd-Smith JO, de Wit E, Munster VJ. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020;382:1564–1567.
    1. 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:e133–e134.
    1. Janda L, Mihalčin M, Šťastná M. Is a healthy microbiome responsible for lower mortality in COVID-19? Biologia (Bratisl) 2020:1–11.
    1. Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, Wan Y, Chung ACK, Cheung CP, Chen N, Lai CKC, Chen Z, Tso EYK, Fung KSC, Chan V, Ling L, Joynt G, Hui DSC, Chan FKL, Chan PKS, Ng SC. Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology 2020; 159: 944-955. :e8.
    1. Zuo T, Zhan H, Zhang F, Liu Q, Tso EYK, Lui GCY, Chen N, Li A, Lu W, Chan FKL, Chan PKS, Ng SC. Alterations in Fecal Fungal Microbiome of Patients With COVID-19 During Time of Hospitalization until Discharge. Gastroenterology 2020; 159: 1302-1310. :e5.
    1. Din AU, Mazhar M, Waseem M, Ahmad W, Bibi A, Hassan A, Ali N, Gang W, Qian G, Ullah R, Shah T, Ullah M, Khan I, Nisar MF, Wu J. SARS-CoV-2 microbiome dysbiosis linked disorders and possible probiotics role. Biomed Pharmacother. 2021;133:110947.
    1. Aguila EJT, Cua IHY, Fontanilla JAC, Yabut VLM, Causing MFP. Gastrointestinal Manifestations of COVID-19: Impact on Nutrition Practices. Nutr Clin Pract. 2020;35:800–805.
    1. Oba J, Carvalho WB, Silva CA, Delgado AF. Gastrointestinal manifestations and nutritional therapy during COVID-19 pandemic: a practical guide for pediatricians. Einstein (Sao Paulo) 2020;18:eRW5774.
    1. Dhar D, Mohanty A. Gut microbiota and Covid-19- possible link and implications. Virus Res. 2020;285:198018.
    1. Olaimat AN, Aolymat I, Al-Holy M, Ayyash M, Abu Ghoush M, Al-Nabulsi AA, Osaili T, Apostolopoulos V, Liu SQ, Shah NP. The potential application of probiotics and prebiotics for the prevention and treatment of COVID-19. NPJ Sci Food. 2020;4:17.
    1. ASPEN Nutrition and hydration: Key weapons in the fight against COVID-19. [cited 10 December 2020]. Available from:
    1. Barazzoni R, Bischoff SC, Breda J, Wickramasinghe K, Krznaric Z, Nitzan D, Pirlich M, Singer P endorsed by the ESPEN Council. ESPEN expert statements and practical guidance for nutritional management of individuals with SARS-CoV-2 infection. Clin Nutr. 2020;39:1631–1638.
    1. Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, Hiesmayr M, Mayer K, Montejo JC, Pichard C, Preiser JC, van Zanten ARH, Oczkowski S, Szczeklik W, Bischoff SC. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019;38:48–79.
    1. Dunn CG, Kenney E, Fleischhacker SE, Bleich SN. Feeding Low-Income Children during the Covid-19 Pandemic. N Engl J Med. 2020;382:e40.
    1. Repici A, Maselli R, Colombo M, Gabbiadini R, Spadaccini M, Anderloni A, Carrara S, Fugazza A, Di Leo M, Galtieri PA, Pellegatta G, Ferrara EC, Azzolini E, Lagioia M. Coronavirus (COVID-19) outbreak: what the department of endoscopy should know. Gastrointest Endosc. 2020;92:192–197.
    1. Elshaarawy O, Lashen SA, Makhlouf NA, Abdeltawab D, Zaghloul MS, Ahmed RM, Fathy H, Afifi S, Abdel-Gawad M, Abdelsameea E, Abd-Elsalam S, Mohamed SY, Tag-Adeen M, Tharwat M, Alzamzamy A, Bekhit AN, Eid AM, Awad A, Aamr M, Dayem WAAE, Wifi MN, Alboraie M. Barriers for resuming endoscopy service in the context of COVID-19 pandemic: A multicenter survey from Egypt. World J Gastroenterol. 2020;26:6880–6890.
    1. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, Tong S. Epidemiology of COVID-19 Among Children in China. Pediatrics. 2020;145
    1. Nathan N, Prevost B, Corvol H. Atypical presentation of COVID-19 in young infants. Lancet. 2020;395:1481.
    1. Yang L, Tu L. Implications of gastrointestinal manifestations of COVID-19. Lancet Gastroenterol Hepatol. 2020;5:629–630.
    1. Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, Li P, Hu B, Wang J, Hu C, Jin Y, Niu X, Ping R, Du Y, Li T, Xu G, Hu Q, Tu L. Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study. Am J Gastroenterol. 2020;115:766–773.
    1. Chen R, Yu YL, Li W, Liu Y, Lu JX, Chen F, Zhou Q, Xia ZY, Gao L, Meng QT, Ma D. Gastrointestinal Symptoms Associated With Unfavorable Prognosis of COVID-19 Patients: A Retrospective Study. Front Med (Lausanne) 2020;7:608259.
    1. Zhou Z, Zhao N, Shu Y, Han S, Chen B, Shu X. Effect of Gastrointestinal Symptoms in Patients With COVID-19. Gastroenterology. 2020;158:2294–2297.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir