Abstract
Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.
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Ludvigsson JF. Systematic review of COVID-19 in children show milder cases and a better prognosis than adults. Acta Paediatr. 2020 Mar 23. [Epub ahead of print] https://onlinelibrary.wiley.com/doi/epdf/10.1111/apa.15270. Accessed on April 08, 2020.
Ministry of Health and Family Welfare. Available from: https://www.mohfw.gov.in Accessed on April 08, 2020.
Zimmermann P, Curtis N. Coronavirus Infections in Children Including COVID-19. PIDJ. 2020 Mar 12. [Epub ahead of print]Available from: https://journals.lww.com/pidj/Abstract/onlinefirst/Coronavirus_Infections_in_Children_Including.96251.aspx. Accessed on April 06, 2020.
Pedersen SF, Ho Y. SARS-CoV-2/: A Storm is Raging. JCI. 2020 Mar 27. [Epub ahead of print]. Available from: https://www.jci.org/articles/view/137647/pdf. Accessed on April 05, 2020.
Spychalski P, Blazynska-Spychalska A, Kobiela J. Estimating case fatality rates of COVID-19. Lancet Infect Dis. 2020 Mar 31. [Epub ahead of print]Available from: https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30246-2.pdf. Accessed on April 04, 2020.
Weston S, Frieman MB. COVID-19: Knowns, Unknowns, and Questions. mSphere. 2020 Mar 18. [Epub ahead of print]. Available from: https://msphere.asm.org/content/msph/5/2/e00203-20.full.pdf. Accessed on April 07, 2020.
Brodin P. Why is COVID-19 so mild in children? Acta Paediatr. 2020 Mar 25. [Epub ahead of print]. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/apa.15271. Accessed on April 06, 2020.
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.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
Jiehao C, Jing X, Daojiong L, Lei X, Zhenghai Q, Yuehua Z, et al. A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features. CID. 2020 Feb 28. [Epub ahead of print]. Available from: https://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciaa198/32709823/ciaa198.pdf. Accessed on April 06, 2020.
Cruz A, Zeichner S. COVID-19 in Children: Initial characterization of the pediatric disease. Pediatrics. 2020 Mar. [Epub ahead of print]. Available from: https://pediatrics.aappublications.org/content/pediatrics/early/2020/03/16/peds.2020-0834.1.full-text.pdf. Accessed on April 06, 2020.
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 Mar 13. Available from: https://www.nature.com/articles/s41591-020-0817-4.pdf. Accessed on April 05, 2020. [Epub ahead of print]
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 Mar. Available from: https://pediatrics.aappublications.org/content/pediatrics/early/2020/03/16/peds.2020-0702.1.full-text.pdf. Accessed on April 04, 2020. [Epub ahead of print]
Murray MA, Chotirmall SH. The impact of immunosenescence on pulmonary disease. Hindawi [Internet]. 2015 Jun 24. Available from: http://downloads.hindawi.com/journals/mi/2015/692546.pdf. Accessed on April 06, 2020.
Nickbakhsh S, Mair C, Matthews L, Reeve R, Johnson PCD, Thorburn F, et al. Virus–virus interactions impact the population dynamics of influenza and the common cold. PNAS [Internet]. 2019 Dec 26; 116:27142–50. Available from:https://www.pnas.org/content/pnas/116/52/27142.full.pdf. Accessed on April 04, 2020.
Lee PI, Hu YL, Chen PY, Huang YC, Hsueh PR. Are children less susceptible to COVID-19? JMII [Internet]. 2020 Feb 25;S1684-1182(20)30039-6. Available from: {rs https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102573/}pdf/main.pdf. url Accessed on April 04, 2020.
Sinha IP, Harwood R, Semple MG, Hawcutt DB, Thursfield R, Narayan O, et al. COVID-19 infection in children. Lancet Respir. 2020 Mar 27. Available from: https://www.thelancet.com/action/showPdf?pii=S2213-2600%2820%2930152-1. Accessed on April 05, 2020. [Epub ahead of print]
Covián C, Fernández-Fierro A, Retamal-Díaz A, Díaz FE, Vasquez AE, Lay MK, et al. BCG-induced cross-protection and development of trained immunity: Implication for vaccine design. Front Immunol [Internet]. 2019 Nov 29;10:2806. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896902/pdf/fimmu-10-02806.pdf. Accessed on April 04, 2020.
Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 Infection in children. NEJM. 2020 Mar 18. Available from: https://www.nejm.org/doi/pdf/10.1056/NEJMc2005073?articleTools=true.Accessed on April 05, 2020. [Epub ahead of print]
Cao Q, Chen Y, Chen C, Chiu C. SARS-CoV-2 Infection in children: Transmission dynamics and clinical charateristics. J Formos Med Assoc. 2020;119:670–673.
Revised Guidelines on Clinical Management of COVID -19 [Internet]. Ministry of Health and Family Welfare. Available from: https://www.mohfw.gov.in/pdf/RevisedNationalClinicalManagementGuidelineforCOVID1931032020.pdf Accessed April 01, 2020.
Advisory to start rapid antibody based blood test for COVID-19 [Internet]. Indian Council of Medical Research. Available from: https://www.mohfw.gov.in/pdf/Advisory&StrategyforUseofRapidAntibodyBasedBloodTest.pdf Accessed April 05, 2020.
Henry BM, Lippi G, Plebani M. Laboratory abnormalities in children with novel coronavirus disease 2019. CCLM. 2020 Mar 16. Available from: https://www.degruyter.com/downloadpdf/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0272/article-10.1515-cclm-2020-0272.xml. Accessed on April 05, 2020. [Epub ahead of print]
Kelvin AA, Halperin S. COVID-19 in children: the link in the transmission chain. Lancet Infect Dis. 2020 Mar 25. Available from: https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930236-X. Accessed on April 06, 2020. [Epub ahead of print]
Li B, Shen J, Li L, Yu C. Radiographic and Clinical Features of Children with 2019 Novel Coronavirus (COVID-19) Pneumonia. Indian Pediatr. 2020 Apr 07. Available from: https://www.indianpediatrics.net/CONVID29.03.2020/RP-00156.pdf Accessed on April 08, 2020. [Epub ahead of print]
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. Pediatric Pulmonology. 2020 Mar 5. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1002/ppul.24718. Accessed on April 05, 2020. [Epub ahead of print]
Mahallawi W, Khabour O, Zhang Q, Makhdoum H, Suliman B. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018;104:8–13.
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.
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 Mar 25. Available from: https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930198-5. Accessed on April 05, 2020. [Epub ahead of print]
Russel CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395:473–5.
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 invitro. Antiviral Res. 2020 Apr 03. Available from: https://www.sciencedirect.com/science/article/pii/S0166354220302011/pdfft?md5=bd2a8d1cfbe3680f2d405b4a62642a15&pid=1-s2.0-S0166354220302011-main.pdf. Accessed on April 05, 2020. [Epub ahead of print]
Chinese Clinical Trial Registry. A multicenter, randomized control trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19). 2020 Feb 13. Available from: http://www.chictr.org.cn/showprojen.aspx?proj=49409. Accessed April 05, 2020.
Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020;395:E30–E31. Available from: https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930304-4. Accessed on April 05, 2020.
Chawla D, Chirla D, Dalwai S, Deorari AK, Ganatra A, Gandhi A, et al. Perinatal-Neonatal Management of COVID-19 Infection - Guidelines of the Federation of Obstetric and Gynecological Societies of India (FOGSI), National Neonatology Forum of India (NNF), and Indian Academy of Pediatrics (IAP). Indian Pediatr. 2020 Apr 01. Available from: www.indianpediatrics.net/CONVID29.03.2020/RECOMM-00154.pdf Accessed on April 06, 2020.
Landman A, Feetham L, Stuckey D. Cancer patients in SARS-CoV-2 infection: A nationwide analysis in China. Lancet Oncol. 2020;21:335–7.
Antiga LD. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. AASLD. 2020 Mar 20. Available from: https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/lt.25756. Accessed on April 05, 2020. [Epub ahead of print]
British Paediatric Allergy Immunity and Infection Group. BPAIIG Position Statement: Sars-CoV-2 Treatment Guidance version 1.2. Available from: https://www.bpaiig.org/news-bpaiig-position-statement-sars-cov-2-treatment-guidance-version-12. Accessed April 06, 2020.
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Contributors: SB, AVR- Initiated the preparation of the manuscript;NMR: Substantial contribution to the conception and design of the work, and prepared and finalized the draft; SB, AVR, AG, MR-Substantial contributions to the acquisition, analysis, and interpretation of data for the work, SB, AVR, A G, MR-Revising it critically for important intellectual content;SB, NMR, AG, MR, AVR: Final approval of the version to be published, and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Balasubramanian, S., Rao, N.M., Goenka, A. et al. Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not. Indian Pediatr 57, 435–442 (2020). https://doi.org/10.1007/s13312-020-1819-5
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DOI: https://doi.org/10.1007/s13312-020-1819-5