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Clinical overview for pediatric population with SARS-CoV-2 and care: review

Cuadro clínico para población pediátrica con SARS-CoV-2 cuidado: revisión

ABSTRACT

Objective:

To identify in the scientific literature the clinical overview of the pediatric population that tested positive for SARS-CoV-2 and care recommendations and recommendations among children who tested positive for SARS-CoV-2 in the scientific literature.

Method:

Rapid review based on the guidelines of the Joana Briggs Institute: elaboration of the research question, structured search of the literature in April 2020, in nine databases, selection and critical analysis of the eighteen primary studies (using two instruments to assess methodological quality), elaboration of the synthesis, incorporation of suggestions and dissemination.

Result:

The most frequent clinical overview was respiratory, gastrointestinal symptoms and fever. The images showed irregular frosted glass opacification. It is recommended to screen the pediatric population and family members who show signs and symptoms and to adopt isolation for more than fourteen days.

Conclusion:

The clinical overview in pediatric population is varied, not exclusively with respiratory symptoms, and a significant number of asymptomatic patients. The importance of new investigations is highlighted, such as randomized clinical trial or cohort studies, identifying their participation in the transmission of COVID-19.

Keywords:
Child; Coronavirus infections; Signs and symptoms; Respiratory tract diseases

RESUMEN

Objetivo:

Identificar en la literatura científica el estado clínico de la población pediátrica que probó positivo para el SARS-CoV-2 y las recomendaciones de atención.

Método:

Revisión rápida basada en las directrices del Instituto Joana Briggs: elaboración de la pregunta de investigación, búsqueda estructurada de la literatura en abril de 2020, en nueve bases de datos, selección y análisis crítico de los dieciocho estudios primarios (utilizando dos instrumentos para evaluar la calidad metodológica), elaboración de la síntesis, incorporación de sugerencias y difusión.

Resultado:

El cuadro clínico más frecuente fue respiratorio, síntomas gastrointestinales y fiebre. Las imágenes mostraron opacificación irregular de vidrio esmerilado. Se recomienda evaluar a población pediátrica y familiares que muestran signos y síntomas y adoptar aislamiento durante más de catorce días.

Conclusiones:

El cuadro clínico en la población pediátrica es variado, no exclusivamente con síntomas respiratorios, y un número importante de pacientes asintomáticos. Se destaca la importancia de nuevas investigaciones, como ensayos clínicos aleatorizados o estudios de cohorte, identificando su participación en la transmisión del COVID-19.

Palabras clave:
Niño; Infecciones por coronavirus; Signos y síntomas; Enfermedades respiratorias

RESUMO

Objetivo:

Identificar, na literatura científica, o quadro clínico da população pediátrica que testou positivo para SARS-CoV-2 e recomendações de cuidados.

Método:

Revisão rápida baseada nas diretrizes da Joana Briggs Institute: elaboração da pergunta de investigação, busca estruturada da literatura no mês de abril de 2020, em nove bases de dados, seleção e análise crítica dos dezoito estudos primários (utilizando dois instrumentos para avaliação da qualidade metodológica), elaboração da síntese, incorporação das sugestões e divulgação.

Resultado:

O quadro clínico mais frequente foi sintomas respiratórios, gastrointestinais e febre. As imagens demonstraram opacificação irregular de vidro fosco. Recomenda-se triagem da população pediátrica e familiares que apresentam sinais e sintomas e adotar isolamento por período superior a quatorze dias.

Conclusão:

Quadro clínico na população pediátrica é variado, não exclusivamente com sintomas respiratórios, e número significativo de assintomáticos. Destaca-se importância de novas investigações, como ensaios clínicos randomizados ou estudos de coorte, identificando a participação dessas na transmissão da COVID-19.

Palavras-chave:
Criança; Infecções por coronavirus; Sinais e sintomas; Doenças respiratórias

INTRODUCTION

In December 2019, the World Health Organization (WHO) was alerted to several cases of pneumonia in the city of Wuhan, province of Hubei, People's Republic of China. The following month, Chinese authorities confirmed that they had identified a new type of coronavirus named SARS-CoV-2, which causes the COVID-19 disease1Organização Panamericana da Saúde [Internet]. Brasília, DF: OPAS; c2020-2021 [cited 2020 Apr 30]. Histórico da pandemia de COVID-19; [about 1 screen]. Available from: Available from: https://www.paho.org/pt/covid19/historico-da-pandemia-covid-19
https://www.paho.org/pt/covid19/historic...
.

On March 11, 2020, the WHO, after assessing the spread of the virus, issued situation report 51 and declared that COVID-19 can be characterized as a pandemic2World Health Organization (CH). Coronavirus disease 2019 (COVID-19): situation report - 51 [Internet]. Geneva: WHO;2020 [cited 2020 May 10]. Available from: Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200311-sitrep-51-covid-19.pdf?sfvrsn=1ba62e57_10
https://www.who.int/docs/default-source/...
. Since then, it can be stated that “the COVID-19 pandemic represents one of the greatest global health challenges of this century”3Barreto ML, Barros AJD, Carvalho MS, Codeço CT, Hallal PRC, Medronho RA, et al. O que é urgente e necessário para subsidiar as políticas de enfrentamento da pandemia de COVID-19 no Brasil? Rev Bras Epidemiol. 2020;23:e200032. doi: https://doi.org/10.1590/1980-549720200032
https://doi.org/10.1590/1980-54972020003...
.

SARS-CoV-2 is an emerging contagious pathogen that causes a high incidence of pneumonia in infected individuals. Thus, it is critical to learn more about the clinical characteristics in pediatric patients to diagnose and effectively treat this disease in this population4Qiu 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;20(6):689-96. doi: https://doi.org/10.1016/S1473-3099(20)30198-5
https://doi.org/10.1016/S1473-3099(20)30...
.

Recent epidemiological data consistently suggest that children and adolescents are the minority of diagnosed COVID-19 cases. The WHO defines children as individuals between 0 and 9 years of age and adolescents as individuals between 10 and 19 years of age. However, the WHO also states that most adolescents are included as “child” based on the age adopted by the Convention on the Rights of the Child5World Health Organization (CH). Health for the world’s adolescentes: a second chance in the second decade. Geneva: WHO; 2014 [cited 2020 May 10]. Available from: Available from: https://apps.who.int/iris/bitstream/handle/10665/112750/WHO_FWC_MCA_14.05_eng.pdf?sequence=1&isAllowed=y
https://apps.who.int/iris/bitstream/hand...
. Thus, considering that the publications on this population in the SARS-CoV-2 pandemic do not distinguish by age classification, the terminology “pediatric population” was adopted to classify children and adolescents affected by COVID-19.

A study6Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. 2020;109(6):1088-95. doi: https://doi.org/10.1111/apa.15270
https://doi.org/10.1111/apa.15270 ...
found that children account for 1% to 5% of confirmed cases. In Canada, on April 25, children under the age of 19 accounted for 4.7% of confirmed cases7Public Health Agency of Canada. Coronavirus Disease 2019 (COVID-19): Daily Epidemiology Update: updated April 25. Ottawa; 2020. . In the United States of America (USA), children accounted for only 1.7% of all cases8CDC COVID-19 Response Team. Coronavirus disease 2019 in children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-6. doi: https://doi.org/10.15585/mmwr.mm6914e4
https://doi.org/10.15585/mmwr.mm6914e4...
. On April 15, the Korea Disease Control and Prevention Agency tested a fairly representative population. Of all the individuals that tested positive for COVID-19, 6.49% were children under 19 years old (1.25% aged 0-9 years and 5.37% aged 10-19)9Korean Center for Disease and Control and Prevention [Internet]. Cheongju: KDCA; c2020-2021 [cited 2020 May 10]. Press release; [about 80 screens]. Available from: Available from: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030
https://www.cdc.go.kr/board/board.es?mid...
. Data from Latin American countries are not yet widely available. In Brazil, among the confirmed COVID-19 deaths, 0.7% were individuals under 19 years of age, on April 26, according to data of the epidemiological bulletin of the Secretariat of Health Inspection10Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Bol Epidemiol Esp. 2020 [cited 2020 Jun 10];(14):1-48. Available from: Available from: https://portalarquivos.saude.gov.br/images/pdf/2020/April/27/2020-04-27-18-05h-BEE14-Boletim-do-COE.pdf
https://portalarquivos.saude.gov.br/imag...
.

In a case series involving 1,391 children at the Wuhan Children's Hospital, 171 (12.3%) were diagnosed with SARS-CoV-2 and mostly presented with fever, cough, and pharyngeal erythema; moreover, the most frequent radiological finding among these confirmed cases was bilateral ground-glass opacity (32.7%)11Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. New Engl J Med. 2020;382(17):663-5. doi: https://doi.org/10.1056/NEJMc2005073
https://doi.org/10.1056/NEJMc2005073...
. In another study conducted in the Zhejiang province of China, the main clinical characteristics of COVID-19 in children were fever, dry cough, and pneumonia4Qiu 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;20(6):689-96. doi: https://doi.org/10.1016/S1473-3099(20)30198-5
https://doi.org/10.1016/S1473-3099(20)30...
.

Although the pediatric population is not the highest risk group for COVID-19, the physical consequences and those arising from preventive measures such as social distancing and isolation have directly affected their mental health and access to preventive actions, such as immunization, thus making this group more vulnerable12Aydogdu ALF. Saúde mental das crianças durante a pandemia causada pelo novo coronavírus: revisão integrativa. J Health NPEPS. 2020 [cited 2020 Apr 30];5(2). Available from: Available from: https://periodicos.unemat.br/index.php/jhnpeps/article/view/4891/3779
https://periodicos.unemat.br/index.php/j...
-13Toso BRGO, Viera CS, Furtado MCC, Bonati PCR. Ações de Enfermagem no cuidado à criança na atenção primária durante a pandemia de COVID-19. Rev Soc Bras Enferm Pediatr. 2020;20(spe):6-15. doi: https://doi.org/10.31508/1676-3793202000000122
https://doi.org/10.31508/1676-3793202000...
. Given the challenges involved in reaching the Global Sustainable Development Goals 2015-2030 established by the United Nations Organization, the achievement of goal 3 (ensuring a healthy life and well-being for all, at all ages)14United Nations (US). Resolution adopted by the General Assembly on 25 September 2015: Transforming our world: the 2030 Agenda for Sustainable Development [Internet]. Nuw York: UM; 2015 [cited 2020 Apr 27]. Available from: Available from: https://www.un.org/ga/search/view_doc.asp?symbol=A/RES/70/1⟪=E
https://www.un.org/ga/search/view_doc.as...
demands further studies and the systemization of available data to guide health actions and, in particular, the practices of nursing professionals.

A large-scale national study with 115 pediatric cases concluded that "knowledge of the particular characteristics of clinical manifestations in children can contribute to the diagnosis and management of COVID-19 cases in children and adolescents”15Rabha AC, Oliveira Junior FI, Oliveira TA, Cesar RG, Fongaro G, Mariano RF, et al. Clinical manifestations of children and adolescents with COVID-19: report of the first 115 cases from Sabará Hospital Infantile. Rev Paul Pediatr. 2021;39. doi: https://doi.org/10.1590/1984-0462/2021/39/2020305
https://doi.org/10.1590/1984-0462/2021/3...
.

A multicenter research trial conducted with 409 children from Latin American countries revealed a generally more severe form of COVID-19 and a high rate of multisystem inflammatory syndrome compared to other regions of the world, thus highlighting the urgency of more studies on the subject16Antúnez-Montes OY, Escamilla MI, Figueroa-Uribe AF, Arteaga-Menchaca E, Lavariega-Saráchaga M, Salcedo-Lozada P, et al. COVID-19 and multisystem inflammatory syndrome in Latin American children: a multinational study. Pediatr Infect Dis J. 2021 Jan;40(1):e1-6. doi: https://doi.org/10.1097/INF.0000000000002949
https://doi.org/10.1097/INF.000000000000...
.

The current scenario justifies the need for this review to synthesize the clinical manifestations of COVID-19 in the pediatric population with the aim of guiding the clinical practice of health professionals during this pandemic and contributing to the establishment of health care. In this regard, the following guiding questions were observed: what is the clinical status of the pediatric population attended in health care facilities that led to RT-PCR testing and possible detection of SARS-CoV-2 RNA? What are the care recommendations for this group? The aim was to identify, in the scientific literature, the clinical status of the pediatric population that tested positive for SARS-CoV-2 and recommendations for care.

Given the above, in the current context of the pandemic triggered by the novel coronavirus, the systematization of information for the construction of scientific evidence is essential for decision-making, recommendations, elaboration and execution of health education actions, and professional health care training.

METHOD

This is a rapid review based on bibliographic database searches17Munn Z, Lockwood C, Moola S. The Development and use of evidence summaries for point of care information systems: a streamlined rapid review approach. Worldviews Evid Based Nurs. 2015;12(3):131-8. doi: https://doi.org/10.1111/wvn.12094
https://doi.org/10.1111/wvn.12094 ...
-18Featherstone RM, Dryden DM, Foisy M, Guise JM, Mitchell MD, Paynter RA, et al. Advancing knowledge of rapid reviews: an analysis of results, conclusions and recommendations from published review articles examining rapid reviews. Syst Rev. 2015;4:50. doi: https://doi.org/10.1186/s13643-015-0040-4
https://doi.org/10.1186/s13643-015-0040-...
. A rapid review is characterized as an efficient methodological proposal for government, clinical, and/or emergency decision-making and currently considered useful to organize information on the manifestation of COVID-19 in the pediatric population.

The databases of the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Medical Literature Analysis and Retrieval System Online (MEDLINE) were consulted and no systematic reviews were found on the general clinical status of children with COVID-19; moreover, a protocol for a systematic review registered in the archives of the Joanna Briggs Institute (JBI) and in the international database of prospectively registered systematic reviews (PROSPERO) was absent.

Thus, the proposal of the six methodological guidelines for rapid review (RR) was adopted, created by the Joanna Briggs Institute (JBI)19Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, Currie M, Lisy K, Qureshi R, Mattis P, Mu P. Systematic reviews of etiology and risk. In: Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide: JBI; 2020. Chapter 7. doi: https://doi.org/10.46658/JBIMES-20-08
https://doi.org/10.46658/JBIMES-20-08...
, which consists of setting the research question, specifying literature selection methods, detailing the data extraction procedure, evaluating the results according to their pertinence and validity, critical analysis, and synthesis of the conclusions. For the first guideline, the research question was based on the PICO strategy20Stone PW. Popping the (PICO) question in research and evidence-based practice. Appl Nurs Res. 2002;15(3):197-8. doi: https://doi.org/10.1053/apnr.2002.34181
https://doi.org/10.1053/apnr.2002.34181 ...
, in which P (patient population) refers to the pediatric population submitted to RT-PCR (reverse-transcriptase polymerase chain reaction) testing, leading to detection of SARS-CoV-2 RNA; I (intervention) refers to the clinical status of the pediatric population and recommendations for care; C (comparison) not applicable; and O (outcomes) refers to established conduct and interventions. Therefore, the following guiding questions were elaborated for the present study: what is the clinical status of the pediatric population attended in health care facilities, which led to RT-PCR testing, and was SARS-CoV-2 RNA detected? What are the care recommendations for this group?

Then, the search strategies were established, according to the specific characteristics of each database, in order to obtain the largest possible number of primary studies of interest. The inclusion criteria were scientific articles on the clinical status of the pediatric population attended in health care facilities who tested positive (RT-PCR) for the novel coronavirus; participants of the investigated studies under the age of 19 years, with or without pre-existing comorbidities; reports of primary cases and case series published from 2019 to 2020, without language restriction, and studies with human participants. Systematic reviews and grey literature were excluded.

The search terms were words or expressions that comprised health-based descriptors (controlled words), which served as a reference for the database searches, leading to replacement of the keyword “pediatric population” with “Infant, Newborn” or “Infant” or “Child, Preschool” since production on the subject does not differentiate results by age groups. Each database search involved a different strategy that allowed the largest collection of articles and included the Boolean operators AND and OR for combination. The searched databases were Virtual Health Library ("BVS"), Latin America and the Caribbean Literature on Health Sciences ("LILACS") via BVS, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PUBMED, Web of Science, Scientific Electronic Library Online (SCIELO), EMBASE, Medline via Pubmed, and IBECS via BVS (Chart 1).

Chart 1 -
Strategies used to search the bibliographic databases and frequency of references

The guideline that corresponds to the selection and critical analysis of the studies was subdivided into stages. Searching and selection were performed by one of the authors, a neonatology nurse, initially on April 20, followed by May 02, 2020, with application of the inclusion criteria and use of the flow diagram PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)21Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009;6(7):e1000097. doi: https://doi.org/10.1371/journal.pmed.1000097
https://doi.org/10.1371/journal.pmed.100...
(Figure 1). All selected references were entered into Mendeley® software to identify duplicate articles.

The methodological quality of the studies was assessed by the authors with expertise in epidemiology using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for case reports19Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, Currie M, Lisy K, Qureshi R, Mattis P, Mu P. Systematic reviews of etiology and risk. In: Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. Adelaide: JBI; 2020. Chapter 7. doi: https://doi.org/10.46658/JBIMES-20-08
https://doi.org/10.46658/JBIMES-20-08...
and the Institute of Health Economics (IHE) quality appraisal checklist for assessing case series22Guo B, Moga C, Harstall C, Schopflocher D. A principal component analysis is conducted for a case series quality appraisal checklist. J Clin Epidemiol. 2016;69:199-207.e2. doi: https://doi.org/10.1016/j.jclinepi.2015.07.010
https://doi.org/10.1016/j.jclinepi.2015....
. The first tool evaluates the methodological quality of case reports and the second tool evaluates the methodological quality of case series. The quality of the studies was classified using the following categories: low (score up to 49.0%), moderate (score between 50.0% and 70.0%), and high (score above 70.0%)23Azevedo YJ de, Ledesma ALL, Pereira LV, Oliveira CA, Bahmad Junior F, Azevedo YJ de, et al. Vestibular implant: does it really work? a systematic review. Braz J Otorhinolaryngol. 2019;85(6):788-98. doi: https://doi.org/10.1016/j.bjorl.2019.07.011
https://doi.org/10.1016/j.bjorl.2019.07....
.

Figure 1 -
Identification, selection, and inclusion of studies in the review of the primary study selection process

The selected articles were critically analyzed through data extraction using an instrument built by the team with the following information: reference, country, objective, methodological factors (type of study, participants, locus, collection instruments, ethical aspects, and analysis proposal), results (profile of participants, clinical manifestations, type and results of diagnostic tests, interventions, and outcome), and recommendations or implications.

The data synthesis for the primary studies was prepared from the complete and impartial interpretation of these studies. The presentation comprised a quantitative description of the identified findings, justification of exclusions after reading the title, abstract and full text, and final sample. Then, the charts, figure, and table of results were created and presented. Finally, the methodological limitations of the rapid review were reported.

The ethical aspects were observed by duly registering the references with year of publication of the study and by maintaining the ideas of the authors of the publications used in the development of this study.

RESULTS

In the rapid review, 228 articles were identified on April 20, and 232 articles were identified on May 02, 2020, from the systematic search on the established databases. In the investigated period, the following number of articles were found: 20 in PUBMED, 0 in SCIELO, 22 in LILACS via Virtual Health Library ("BVS"), 20 in CINAHL, 370 Medline, 11 in IBECS via BVS, 2 in EMBASE, and 15 in Web of Science. Among these studies, 29 articles were excluded due to duplication and 386 were excluded because the title did not match the keywords of the research strategy, resulting in 45 articles in this stage. After reading the abstracts, 20 articles were excluded and after reading the full text, 7 articles were eliminated, based on the inclusion and exclusion criteria.

The studies included after application of all the criteria totaled 18. Of these articles, 9 were case reports24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-32Zhang YH, Lin DJ, Xiao MF, Wang JC, Wei Y, Lei ZX, et al. 2019-novel coronavirus infection in a three-month-old baby. Zhonghua Er Ke Za Zhi. 2020;58(3):182-4. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.03.004
https://doi.org/10.3760/cma.j.issn.0578-...
and 9 were case series33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
and they were all based on methodologies with descriptive quantitative approaches. The studies were conducted in China (13), Korea (1), Italy (1), Lebanon (1), Iran (1), and Spain (1). Most of the studies were written in English (14), 3 in Mandarin, and 1 in Spanish. The locus of all the studies were hospitals and the data collection instruments were observation and case records. Regarding the ethical aspects, 7 articles28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
,33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
-36Shi Y, Wang X, Liu G, Zhu Q, Wang J, Yu H, et al. A quickly, effectively screening process of novel corona virus disease 2019 (COVID-19) in children in Shanghai, China. Ann Transl Med. 2020;8(5):241. doi: https://doi.org/10.21037/atm.2020.03.22
https://doi.org/10.21037/atm.2020.03.22...
,39Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World J Pediatr. 2020;16(3):251-9. doi: https://doi.org/10.1007/s12519-020-00354-4
https://doi.org/10.1007/s12519-020-00354...
-40Xia 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;55(5):1169-74. doi: https://doi.org/10.1002/ppul.24718
https://doi.org/10.1002/ppul.24718...
included information on the protocols, while 11 did not report any procedures24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-27Lin J, Duan J, Tan T, Fu Z, Dai J. The isolation period should be longer: lesson from a child infected with SARS-CoV-2 in Chongqing, China. Pediatr Pulmonol. 2020;55(6):E6-E9. doi: https://doi.org/10.1002/ppul.24763
https://doi.org/10.1002/ppul.24763...
,29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
-32Zhang YH, Lin DJ, Xiao MF, Wang JC, Wei Y, Lei ZX, et al. 2019-novel coronavirus infection in a three-month-old baby. Zhonghua Er Ke Za Zhi. 2020;58(3):182-4. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.03.004
https://doi.org/10.3760/cma.j.issn.0578-...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
-38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
,41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
. The data of 208 children, aged from 1 day to 15 years, were analyzed, as shown in Table 1.

Table 1 -
Strategies used to search the bibliographic database and frequency of references

In the methodological quality assessment, only one study presented low methodological quality, with a score of 28.6%30Li Y, Guo FF, Cao Y, Li LF, Guo YJ. Insight into COVID-2019 for pediatricians. Pediatr Pulmonol. 2020;55(5):E1-E4. doi: https://doi.org/10.1002/ppul.24734
https://doi.org/10.1002/ppul.24734...
. In all, 17 studies showed high methodological quality: 3 reached 100.0%27Lin J, Duan J, Tan T, Fu Z, Dai J. The isolation period should be longer: lesson from a child infected with SARS-CoV-2 in Chongqing, China. Pediatr Pulmonol. 2020;55(6):E6-E9. doi: https://doi.org/10.1002/ppul.24763
https://doi.org/10.1002/ppul.24763...
-28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
,31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
, 1 reached 90.0%39Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World J Pediatr. 2020;16(3):251-9. doi: https://doi.org/10.1007/s12519-020-00354-4
https://doi.org/10.1007/s12519-020-00354...
, 2 reached 85.7%26Alonso Díaz C, López Maestro M, Moral Pumarega MT, Flores Antón B, Pallás Alonso C. Primer caso de infección neonatal por SARS-CoV-2 en España [letter]. An Pediatr (Barc). 2020;92(4):237-8. doi: https://doi.org/10.1016/j.anpedi.2020.03.002
https://doi.org/10.1016/j.anpedi.2020.03...
.29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
, 2 reached 82.5%35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
.37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
, 2 reached 80.0%36Shi Y, Wang X, Liu G, Zhu Q, Wang J, Yu H, et al. A quickly, effectively screening process of novel corona virus disease 2019 (COVID-19) in children in Shanghai, China. Ann Transl Med. 2020;8(5):241. doi: https://doi.org/10.21037/atm.2020.03.22
https://doi.org/10.21037/atm.2020.03.22...
.38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
, 1 totaled 77.5%34Li W, Cui H, Li K, Fang Y, Li S. Chest computed tomography in children with COVID-19 respiratory infection. Pediatr Radiol. 2020;50(6):796-9. doi: https://doi.org/10.1007/s00247-020-04656-7
https://doi.org/10.1007/s00247-020-04656...
, 1 reached 75.0%33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
, 1 obtained 72.5%40Xia 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;55(5):1169-74. doi: https://doi.org/10.1002/ppul.24718
https://doi.org/10.1002/ppul.24718...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
, and 2 reached 71.4%24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-25Canarutto D, Priolo A, Russo G, Pitea M, Vigone MC, Barera G. COVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings. Pediatr Pulmonol. 2020;55(6):E4-E5. doi: https://doi.org/10.1002/ppul.24754
https://doi.org/10.1002/ppul.24754...
(Chart 2).

Chart 2 -
Methodological quality assessment

Of the analyzed articles, the children mostly presented with the following clinical manifestations: respiratory symptoms (cough, runny nose, nasal congestion, rhinitis, polypnea, and rumbling auscultation) 114/208, followed by fever 72/208; gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation) 24/208; sore throat 5/208; chest pain 2/208; headache 1/208; lethargy 1/208; and skin spots 1/208. There were 94 asymptomatic children (Chart 3).

Chart 3 -
Imaging, clinical status, and recommendations addressed in the studies

Among the primary case series, the clinical signs presented were respiratory symptoms such as cough, runny nose, nasal congestion, allergic rhinitis, sputum, respiratory distress, polypnea, rumbling auscultation33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
,35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
; and fever33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
,35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
, as well as gastrointestinal symptoms such as nausea, vomiting, diarrhea, constipation35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
,38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
; sore throat40Xia 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;55(5):1169-74. doi: https://doi.org/10.1002/ppul.24718
https://doi.org/10.1002/ppul.24718...
; chest pain41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
; headache39Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World J Pediatr. 2020;16(3):251-9. doi: https://doi.org/10.1007/s12519-020-00354-4
https://doi.org/10.1007/s12519-020-00354...
; and cases of asymptomatic children33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
-34Li W, Cui H, Li K, Fang Y, Li S. Chest computed tomography in children with COVID-19 respiratory infection. Pediatr Radiol. 2020;50(6):796-9. doi: https://doi.org/10.1007/s00247-020-04656-7
https://doi.org/10.1007/s00247-020-04656...
,38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
,41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
.

With regard to the case reports with at least two children, respiratory symptoms such as cough, rhinitis, sputum, respiratory distress, difficulty breathing, without coughing or sneezing24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-25Canarutto D, Priolo A, Russo G, Pitea M, Vigone MC, Barera G. COVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings. Pediatr Pulmonol. 2020;55(6):E4-E5. doi: https://doi.org/10.1002/ppul.24754
https://doi.org/10.1002/ppul.24754...
,27Lin J, Duan J, Tan T, Fu Z, Dai J. The isolation period should be longer: lesson from a child infected with SARS-CoV-2 in Chongqing, China. Pediatr Pulmonol. 2020;55(6):E6-E9. doi: https://doi.org/10.1002/ppul.24763
https://doi.org/10.1002/ppul.24763...
-28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
,30Li Y, Guo FF, Cao Y, Li LF, Guo YJ. Insight into COVID-2019 for pediatricians. Pediatr Pulmonol. 2020;55(5):E1-E4. doi: https://doi.org/10.1002/ppul.24734
https://doi.org/10.1002/ppul.24734...
-31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
were listed, and polypnea occurred on the ninth day of a new-born26Alonso Díaz C, López Maestro M, Moral Pumarega MT, Flores Antón B, Pallás Alonso C. Primer caso de infección neonatal por SARS-CoV-2 en España [letter]. An Pediatr (Barc). 2020;92(4):237-8. doi: https://doi.org/10.1016/j.anpedi.2020.03.002
https://doi.org/10.1016/j.anpedi.2020.03...
. Other symptoms included fever25Canarutto D, Priolo A, Russo G, Pitea M, Vigone MC, Barera G. COVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings. Pediatr Pulmonol. 2020;55(6):E4-E5. doi: https://doi.org/10.1002/ppul.24754
https://doi.org/10.1002/ppul.24754...
,28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
-31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
, gastrointestinal symptoms such as diarrhea29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
, lethargy31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
, and skin spots24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
,31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
, and some cases of asymptomatic children27Lin J, Duan J, Tan T, Fu Z, Dai J. The isolation period should be longer: lesson from a child infected with SARS-CoV-2 in Chongqing, China. Pediatr Pulmonol. 2020;55(6):E6-E9. doi: https://doi.org/10.1002/ppul.24763
https://doi.org/10.1002/ppul.24763...
,30Li Y, Guo FF, Cao Y, Li LF, Guo YJ. Insight into COVID-2019 for pediatricians. Pediatr Pulmonol. 2020;55(5):E1-E4. doi: https://doi.org/10.1002/ppul.24734
https://doi.org/10.1002/ppul.24734...
.

The results of the laboratory tests showed alterations in the leukogram. Cultures of nasopharynx24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
,35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
, blood25Canarutto D, Priolo A, Russo G, Pitea M, Vigone MC, Barera G. COVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings. Pediatr Pulmonol. 2020;55(6):E4-E5. doi: https://doi.org/10.1002/ppul.24754
https://doi.org/10.1002/ppul.24754...
,28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
-29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
,31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
-32Zhang YH, Lin DJ, Xiao MF, Wang JC, Wei Y, Lei ZX, et al. 2019-novel coronavirus infection in a three-month-old baby. Zhonghua Er Ke Za Zhi. 2020;58(3):182-4. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.03.004
https://doi.org/10.3760/cma.j.issn.0578-...
,38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
,41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
, urine25Canarutto D, Priolo A, Russo G, Pitea M, Vigone MC, Barera G. COVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings. Pediatr Pulmonol. 2020;55(6):E4-E5. doi: https://doi.org/10.1002/ppul.24754
https://doi.org/10.1002/ppul.24754...
,27Lin J, Duan J, Tan T, Fu Z, Dai J. The isolation period should be longer: lesson from a child infected with SARS-CoV-2 in Chongqing, China. Pediatr Pulmonol. 2020;55(6):E6-E9. doi: https://doi.org/10.1002/ppul.24763
https://doi.org/10.1002/ppul.24763...
-29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
,31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
-32Zhang YH, Lin DJ, Xiao MF, Wang JC, Wei Y, Lei ZX, et al. 2019-novel coronavirus infection in a three-month-old baby. Zhonghua Er Ke Za Zhi. 2020;58(3):182-4. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.03.004
https://doi.org/10.3760/cma.j.issn.0578-...
,38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
, and feces28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
-29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
,31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
,32Zhang YH, Lin DJ, Xiao MF, Wang JC, Wei Y, Lei ZX, et al. 2019-novel coronavirus infection in a three-month-old baby. Zhonghua Er Ke Za Zhi. 2020;58(3):182-4. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.03.004
https://doi.org/10.3760/cma.j.issn.0578-...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
-38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
were also performed. In some cultures, the presence of the virus was detected in the nasopharynx24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-26Alonso Díaz C, López Maestro M, Moral Pumarega MT, Flores Antón B, Pallás Alonso C. Primer caso de infección neonatal por SARS-CoV-2 en España [letter]. An Pediatr (Barc). 2020;92(4):237-8. doi: https://doi.org/10.1016/j.anpedi.2020.03.002
https://doi.org/10.1016/j.anpedi.2020.03...
,28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
,31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
-33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
,35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
and in the feces28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
-30Li Y, Guo FF, Cao Y, Li LF, Guo YJ. Insight into COVID-2019 for pediatricians. Pediatr Pulmonol. 2020;55(5):E1-E4. doi: https://doi.org/10.1002/ppul.24734
https://doi.org/10.1002/ppul.24734...
,32Zhang YH, Lin DJ, Xiao MF, Wang JC, Wei Y, Lei ZX, et al. 2019-novel coronavirus infection in a three-month-old baby. Zhonghua Er Ke Za Zhi. 2020;58(3):182-4. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.03.004
https://doi.org/10.3760/cma.j.issn.0578-...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
-38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
.

Regarding alterations identified in computed tomography, the images showed irregular ground-glass opacity in 80 children29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
,34Li W, Cui H, Li K, Fang Y, Li S. Chest computed tomography in children with COVID-19 respiratory infection. Pediatr Radiol. 2020;50(6):796-9. doi: https://doi.org/10.1007/s00247-020-04656-7
https://doi.org/10.1007/s00247-020-04656...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
.

The established interventions were hospitalization of the child in isolation ward24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-25Canarutto D, Priolo A, Russo G, Pitea M, Vigone MC, Barera G. COVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings. Pediatr Pulmonol. 2020;55(6):E4-E5. doi: https://doi.org/10.1002/ppul.24754
https://doi.org/10.1002/ppul.24754...
,27Lin J, Duan J, Tan T, Fu Z, Dai J. The isolation period should be longer: lesson from a child infected with SARS-CoV-2 in Chongqing, China. Pediatr Pulmonol. 2020;55(6):E6-E9. doi: https://doi.org/10.1002/ppul.24763
https://doi.org/10.1002/ppul.24763...
-28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
,30Li Y, Guo FF, Cao Y, Li LF, Guo YJ. Insight into COVID-2019 for pediatricians. Pediatr Pulmonol. 2020;55(5):E1-E4. doi: https://doi.org/10.1002/ppul.24734
https://doi.org/10.1002/ppul.24734...
-31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
,33Feng K, Yun Y, Wang X, Yang G, Zheng Y, Lin C, et al. [Analysis of CT features of 15 Children with 2019 novel coronavirus infection]. Zhonghua Er Ke Za Zhi. 2020;58:E007. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.0007
https://doi.org/10.3760/cma.j.issn.0578-...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
or neonatal/pediatric intensive care unit26Alonso Díaz C, López Maestro M, Moral Pumarega MT, Flores Antón B, Pallás Alonso C. Primer caso de infección neonatal por SARS-CoV-2 en España [letter]. An Pediatr (Barc). 2020;92(4):237-8. doi: https://doi.org/10.1016/j.anpedi.2020.03.002
https://doi.org/10.1016/j.anpedi.2020.03...
,29Zeng LK, Tao XW, Yuan WH, Wang J, Liu X, Liu ZS. [First case of neonate with COVID-19 in China]. Zhonghua Er Ke Za Zhi. 2020;58(4):279-80. Chinese. doi: https://doi.org/10.3760/cma.j.cn112140-20200212-00081
https://doi.org/10.3760/cma.j.cn112140-2...
,35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
,39Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World J Pediatr. 2020;16(3):251-9. doi: https://doi.org/10.1007/s12519-020-00354-4
https://doi.org/10.1007/s12519-020-00354...
,41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
, depending on the clinical status. In cases in which the family tested positive for COVID-19, the child remained hospitalized and the family remained in monitored home isolation31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
; the child was discharged after a period of hospitalization and remained in home isolation with the family for 14 days24Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. doi: https://doi.org/10.1080/23744235.2020.1747634
https://doi.org/10.1080/23744235.2020.17...
-25Canarutto D, Priolo A, Russo G, Pitea M, Vigone MC, Barera G. COVID-19 infection in a paucisymptomatic infant: raising the index of suspicion in epidemic settings. Pediatr Pulmonol. 2020;55(6):E4-E5. doi: https://doi.org/10.1002/ppul.24754
https://doi.org/10.1002/ppul.24754...
,27Lin J, Duan J, Tan T, Fu Z, Dai J. The isolation period should be longer: lesson from a child infected with SARS-CoV-2 in Chongqing, China. Pediatr Pulmonol. 2020;55(6):E6-E9. doi: https://doi.org/10.1002/ppul.24763
https://doi.org/10.1002/ppul.24763...
,36Shi Y, Wang X, Liu G, Zhu Q, Wang J, Yu H, et al. A quickly, effectively screening process of novel corona virus disease 2019 (COVID-19) in children in Shanghai, China. Ann Transl Med. 2020;8(5):241. doi: https://doi.org/10.21037/atm.2020.03.22
https://doi.org/10.21037/atm.2020.03.22...
; or the entire family was admitted to hospital26Alonso Díaz C, López Maestro M, Moral Pumarega MT, Flores Antón B, Pallás Alonso C. Primer caso de infección neonatal por SARS-CoV-2 en España [letter]. An Pediatr (Barc). 2020;92(4):237-8. doi: https://doi.org/10.1016/j.anpedi.2020.03.002
https://doi.org/10.1016/j.anpedi.2020.03...
,28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
,37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
.

The outcome of 201 cases was recovery and hospital discharge; however, 5 children were hospitalized again37Su L, Ma X, Yu H, Zhang Z, Bian P, Han Y, et al. The different clinical characteristics of corona virus disease cases between children and their families in China: the character of children with COVID-19. Emerg Microbes Infect. 2020;9(1):707-13. doi: https://doi.org/10.1080/22221751.2020.1744483
https://doi.org/10.1080/22221751.2020.17...
and 2 remained hospitalized for longer than the conclusion of the study41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
.

DISCUSSION

Most of the pediatric population that tested positive for SARS-CoV-2 identified in this review presented with respiratory symptoms, fever, and gastrointestinal symptoms. Similar results were found in other studies4Qiu 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;20(6):689-96. doi: https://doi.org/10.1016/S1473-3099(20)30198-5
https://doi.org/10.1016/S1473-3099(20)30...
,8CDC COVID-19 Response Team. Coronavirus disease 2019 in children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-6. doi: https://doi.org/10.15585/mmwr.mm6914e4
https://doi.org/10.15585/mmwr.mm6914e4...
,11Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. New Engl J Med. 2020;382(17):663-5. doi: https://doi.org/10.1056/NEJMc2005073
https://doi.org/10.1056/NEJMc2005073...
. According to a meta-analysis, COVID-19 manifests itself with a rapid and progressive course of fever, cough, and dyspnea, with similarities to other viral respiratory pathogens42Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Vol. 34, Travel Med Infect Dis. 2020;34:101623. doi: https://doi.org/10.1016/j.tmaid.2020.101623
https://doi.org/10.1016/j.tmaid.2020.101...
. Regarding respiratory symptoms, the centers for disease control and prevention8CDC COVID-19 Response Team. Coronavirus disease 2019 in children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-6. doi: https://doi.org/10.15585/mmwr.mm6914e4
https://doi.org/10.15585/mmwr.mm6914e4...
reported cough in 54% and shortness of breath in 13% of pediatric patients. In a study conducted in China with 171 children, cough was identified in 48.5% and pharyngeal erythema in 46.2% of pediatric patients, together with other symptoms11Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. New Engl J Med. 2020;382(17):663-5. doi: https://doi.org/10.1056/NEJMc2005073
https://doi.org/10.1056/NEJMc2005073...
.

With regard to fever, it was observed that the defining parameters of hyperthermia were heterogeneous. According to one study conducted in China, of the 41.5% of the pediatric patients who presented with fever, 58.5% had a temperature below 37.5°C11Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. New Engl J Med. 2020;382(17):663-5. doi: https://doi.org/10.1056/NEJMc2005073
https://doi.org/10.1056/NEJMc2005073...
. A second study also conducted in China found that 36% of children presented with fever based on a reference temperature above 37°C4Qiu 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;20(6):689-96. doi: https://doi.org/10.1016/S1473-3099(20)30198-5
https://doi.org/10.1016/S1473-3099(20)30...
. It is observed that the parameters established for fever do not comply with the WHO reference, in which fever in children is established with a body temperature equal to or greater than 37.5ºC43World Health Organization (CH). Thermal protection of the newborn: a practical guide. Geneva: WHO;1997 [cited 2020 May 10] Available from: Available from: https://apps.who.int/iris/bitstream/handle/10665/63986/WHO_RHT_MSM_97.2.pdf?sequence=1
https://apps.who.int/iris/bitstream/hand...
.

Gastrointestinal symptoms were also identified in other studies4Qiu 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;20(6):689-96. doi: https://doi.org/10.1016/S1473-3099(20)30198-5
https://doi.org/10.1016/S1473-3099(20)30...
,11Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. New Engl J Med. 2020;382(17):663-5. doi: https://doi.org/10.1056/NEJMc2005073
https://doi.org/10.1056/NEJMc2005073...
. Such symptoms should be further investigated, as they are common in other viral infections of the respiratory tract such as respiratory syncytial virus44Ferolla FM, Soffe J, Mistchenko A, Contrini MM, López EL. Impacto clínico-epidemiológico del virus sincicial respiratorio e identificación de factores de riesgo de enfermedad grave en niños hospitalizados por infección respiratoria aguda. Arch Argent Pediatr. 2019;117(4):216-23. doi: https://doi.org/10.5546/aap.2019.eng.216
https://doi.org/10.5546/aap.2019.eng.216...
.

A study comparing infections in children by SARS-CoV, MERS-CoV, and SARS-CoV-2 concluded that the clinical, laboratory and radiological characteristics are similar for all referred coronaviruses45Zimmermann P, Curtis N. Coronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatric Infect Dis J. 2020;39(5):355-68. doi: https://doi.org/10.1097/INF.0000000000002660
https://doi.org/10.1097/INF.000000000000...
. This finding can serve as a guideline for the interventions of health workers in the care of the pediatric population with COVID-19.

It is still not clearly understood why most of the pediatric population presents with a mild clinical status, but it is known that there are numerous mechanisms associated with the fields of immunology, anatomy, and virology46Brodin P. Why is COVID-19 so mild in children? [editorial]. Acta Paediatr. 2020;109(6):102-3. doi: https://doi.org/10.1111/apa.15271https://doi.org/10.1111/apa.15271
https://doi.org/10.1111/apa.15271https:/...
-47Shen KL, Yang YH. Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue. World J Pediatr. 2020;16(3):219-21. doi: https://doi.org/10.1007/s12519-020-00344-6
https://doi.org/10.1007/s12519-020-00344...
. According to some hypotheses, the innate immune response, which is an early immune response of the organism against microorganisms, is more active in children, so they can fight the virus more quickly, even before presenting any symptoms28Park JY, Han MS, Park KU, Kim JY, Choi EH. First pediatric case of coronavirus disease 2019 in Korea. J Korean Med Sci. 2020;35(11):e124. doi: https://doi.org/10.3346/jkms.2020.35.e124
https://doi.org/10.3346/jkms.2020.35.e12...
. Moreover, other scholars have found that SARS-CoV-2 enters cells through specific receptors that are distributed differently by the organism of different populations and, especially in children, the amount and function of these receptors are poorly developed48Hoffmann M, Kleine-Weber H, Krueger N, Mueller MA, Drosten C, Poehlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. Cell. 2020;181(2):271-80.E2. doi: https://doi.org/10.1016/j.cell.2020.02.052
https://doi.org/10.1016/j.cell.2020.02.0...
.

A study concluded that critical pediatric patients with COVID-19 are still rare, but it also stresses the need for early planning considering an increase in pediatric cases49Ong JSM, BChir MB, Tosoni A, Kim YJ, Kissoon N, Murthy S. Coronavirus Disease 2019 in critically ill children: a narrative review of the literature. Pediatr Crit Care Med. 2020;21(7):662-6. doi: https://doi.org/10.1097/PCC.0000000000002376
https://doi.org/10.1097/PCC.000000000000...
.

However, as the pandemic continues to spread, studies reveal greater severity of COVID-19 in the pediatric population, which is now being affected with the most severe form of the disease15Rabha AC, Oliveira Junior FI, Oliveira TA, Cesar RG, Fongaro G, Mariano RF, et al. Clinical manifestations of children and adolescents with COVID-19: report of the first 115 cases from Sabará Hospital Infantile. Rev Paul Pediatr. 2021;39. doi: https://doi.org/10.1590/1984-0462/2021/39/2020305
https://doi.org/10.1590/1984-0462/2021/3...
-16Antúnez-Montes OY, Escamilla MI, Figueroa-Uribe AF, Arteaga-Menchaca E, Lavariega-Saráchaga M, Salcedo-Lozada P, et al. COVID-19 and multisystem inflammatory syndrome in Latin American children: a multinational study. Pediatr Infect Dis J. 2021 Jan;40(1):e1-6. doi: https://doi.org/10.1097/INF.0000000000002949
https://doi.org/10.1097/INF.000000000000...
, correlated with multisystem inflammatory syndrome.

This rapid review showed that 94 asymptomatic children tested positive for COVID-19, which indicates the need to test this population when these children live with or have contact with symptomatic family members. In a study conducted in Singapore, the case of an asymptomatic infant with a positive nasopharyngeal swab was monitored until the sixteenth day of admission, thus demonstrating the complexity of defining incidence of the disease since asymptomatic people can excrete the virus50Kam KQ, Yung CF, Cui L, Lin RTP, Mak TM, Maiwald M, et al. A well infant with Coronavirus Disease 2019 (COVID-19) with high viral load. Clin Infect Dis. 2020;71(15):847-9. doi: https://doi.org/10.1093/cid/ciaa201
https://doi.org/10.1093/cid/ciaa201...
. In this regard, it is important to fully record symptoms in medical forms to prevent any incompleteness of data that may cause cases to be classified as asymptomatic8CDC COVID-19 Response Team. Coronavirus disease 2019 in children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-6. doi: https://doi.org/10.15585/mmwr.mm6914e4
https://doi.org/10.15585/mmwr.mm6914e4...
.

Other findings in the studies of this review result from alterations in the leukogram, positive swabs for oropharynx, and feces. On March 19, 2020, the WHO issued a guideline for laboratory tests that should be requested for people suspected of COVID-19 infection51World Health Organization. Laboratory testing for coronavirus disease 2019 (‎COVID-19)‎ in suspected human cases: interim guidance, 2 March 2020. Geneva: WHO; 2020 [cited 2020 May 15]. Available from: Available from: https://apps.who.int/iris/bitstream/handle/10665/331329/WHO-COVID-19-laboratory-2020.4-eng.pdf?sequence=1&isAllowed=y
https://apps.who.int/iris/bitstream/hand...
. However, the use of different tests in the various countries experiencing the pandemic may make it difficult to compare diagnostic methods. Regarding the rectal swab, a study38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
reported positive test results in eight infected children even after a negative nasopharyngeal swab, which indicates possible fecal-oral transmission46Brodin P. Why is COVID-19 so mild in children? [editorial]. Acta Paediatr. 2020;109(6):102-3. doi: https://doi.org/10.1111/apa.15271https://doi.org/10.1111/apa.15271
https://doi.org/10.1111/apa.15271https:/...
.

Regarding imaging in all the analyzed studies, chest X-ray and CT scans were the most frequently used methods and provided additional information to define the clinical status of COVID-19 in children and the diagnosis. According to some studies, the clinical manifestations viewed on computed tomography in patients diagnosed with COVID-19 reveal abnormalities, even in asymptomatic patients, with rapid evolution of bilateral and/or unilateral ground-glass opacity36Shi Y, Wang X, Liu G, Zhu Q, Wang J, Yu H, et al. A quickly, effectively screening process of novel corona virus disease 2019 (COVID-19) in children in Shanghai, China. Ann Transl Med. 2020;8(5):241. doi: https://doi.org/10.21037/atm.2020.03.22
https://doi.org/10.21037/atm.2020.03.22...
,52Ng M-Y, Lee EYP, Yang J, Yang F, Li X, Wang H, et al. Imaging profile of the COVID-19 infection: radiologic findings and literature review. Radiol Cardiothorac Imaging. 2020;2(1):e200034. doi: https://doi.org/10.1148/ryct.2020200034
https://doi.org/10.1148/ryct.2020200034...
.

Regarding sex, it was not possible to establish whether most of the cases were male or female patients or possible justifications since three articles32Zhang YH, Lin DJ, Xiao MF, Wang JC, Wei Y, Lei ZX, et al. 2019-novel coronavirus infection in a three-month-old baby. Zhonghua Er Ke Za Zhi. 2020;58(3):182-4. Chinese. doi: https://doi.org/10.3760/cma.j.issn.0578-1310.2020.03.004
https://doi.org/10.3760/cma.j.issn.0578-...
,40Xia 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;55(5):1169-74. doi: https://doi.org/10.1002/ppul.24718
https://doi.org/10.1002/ppul.24718...
-41Ma Y-L, Xia S-Y, Wang M, Zhang S-M, DU W-H, Chen Q. [Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):290-3. doi: https://doi.org/10.7499/j.issn.1008-8830.2003016
https://doi.org/10.7499/j.issn.1008-8830...
did not specify the sex of patients. This information is important to better determine the characteristics of vulnerable groups.

The pediatric population participating in the studies mostly presented with the mild form of the disease and evolved to hospital discharge. This finding corroborates the statements of experts on the evolution of the pathology46Brodin P. Why is COVID-19 so mild in children? [editorial]. Acta Paediatr. 2020;109(6):102-3. doi: https://doi.org/10.1111/apa.15271https://doi.org/10.1111/apa.15271
https://doi.org/10.1111/apa.15271https:/...
. A study conducted with French children who presented with signs of severe infection by COVID-19 showed that this population responds positively and quickly against the disease53Nathan N, Prevost B, Corvol H. Atypical presentation of COVID-19 in young infants [corrspondence]. Lancet. 2020;395(10235):1481. doi: https://doi.org/10.1016/S0140-6736(20)30980-6
https://doi.org/10.1016/S0140-6736(20)30...
.

Although children present with asymptomatic or mild forms of the disease, “they represent a substantial source of infection in the community and may play an important role in viral transmission”54Safadi MAP. The intriguing features of COVID-19 in children and its impact on the pandemic. J Pediatr (Rio J). 2020;96(3):265-8. doi: https://doi.org/10.1016/j.jped.2020.04.001
https://doi.org/10.1016/j.jped.2020.04.0...
. This finding could support strategies to control the transmission chain of SARS-CoV-211Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. New Engl J Med. 2020;382(17):663-5. doi: https://doi.org/10.1056/NEJMc2005073
https://doi.org/10.1056/NEJMc2005073...
.

The care interventions for the pediatric population with COVID-19 were hospital admission (in isolation ward, neonatal and pediatric intensive care unit) and home isolation with the family for 14 days. Considering the rapid spread of SARS-CoV-2, isolating children and their families or quarantine are basic public health actions to contain this emerging epidemic50Kam KQ, Yung CF, Cui L, Lin RTP, Mak TM, Maiwald M, et al. A well infant with Coronavirus Disease 2019 (COVID-19) with high viral load. Clin Infect Dis. 2020;71(15):847-9. doi: https://doi.org/10.1093/cid/ciaa201
https://doi.org/10.1093/cid/ciaa201...
, prevent overcrowding in health units, and protect risk groups8CDC COVID-19 Response Team. Coronavirus disease 2019 in children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422-6. doi: https://doi.org/10.15585/mmwr.mm6914e4
https://doi.org/10.15585/mmwr.mm6914e4...
. Moreover, these interventions reduce the speed of transmission and contamination by the virus until more effective preventive and therapeutic measures are developed.

The recommendations identified in the studies of this rapid review can be synthesized in terms of practice and research, as follows: (i) give priority to the early identification of characteristics that are specific to the pediatric population and timely treatment to prevent damage to the lungs in the long-term and serious health-related complications; (ii) track cases of infection in the family disease history; (iii) test for SARS-CoV-2 using RT-PCR in the pediatric population with a family member who presents symptoms and signs, as children can be asymptomatic; (iv) isolate the pediatric population and their families for more than fourteen days; (v) test of sputum, pus or oropharynx, and feces samples during the course of the disease until all three tests are negative; and (vi) assess the risk of radiation exposure in children when computed tomography is indicated.

It should be noted that five articles31Mansour A, Atoui R, Kanso K, Mohsen R, Fares Y, Fares J. First case of an infant with COVID-19 in the Middle East. Cureus. 2020;12(4):e7520. doi: https://doi.org/10.7759/cureus.7520
https://doi.org/10.7759/cureus.7520...
,35Liu 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 [correspondence]. New Engl J Med. 2020;382(14):1370-1. doi: https://doi.org/10.1056/NEJMc2003717
https://doi.org/10.1056/NEJMc2003717 ...
-38Xu 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;26(4):502-5. doi: https://doi.org/10.1038/s41591-020-0817-4
https://doi.org/10.1038/s41591-020-0817-...
did not specify recommendations, which is considered a limitation of these studies.

The description of ethical standards was limited to a few studies of the review. In this regard, each country is regulated by its own guidelines; however, it is essential to notify precautions that ensure the dignity and integrity of participants, especially in the context of infectious disease outbreaks55World Health Organization (CH). New guidance on managing ethical issues in infectious disease outbreaks. Geneva: WHO; 2016 [cited 2020 May 15]. Available from: Available from: https://apps.who.int/iris/bitstream/handle/10665/250580/9789241549837-eng.pdf?sequence=1&isAllowed=y
https://apps.who.int/iris/bitstream/hand...
.

Precautions should be taken during breastfeeding, for example, to increase protection against infection, as there is no scientific evidence on the route of transmission to newborns.

Government agencies, health workers, and, in particular, nursing teams should pay extra attention to children in conditions of vulnerability since these conditions, associated with the COVID-19 pandemic, increase the care needs of this population.

In this regard, child primary care should be restructured so as not to suspend assistance provided by children's programs since a study56Roberton T, Carter ED, Chou VB, et al. Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study. Lancet Glob Heal. 2020;8(7):e901-e908. doi: https://doi.org/10.1016/s2214-109x(20)30229-1
https://doi.org/10.1016/s2214-109x(20)30...
indicates that the non-provision of these services may increase the prevalence of additional deaths by 18% to 23%.

This study contributes to knowledge in the area of child health by identifying the clinical status and recommendations adopted in the international literature for the pediatric population with COVID-19 and, therefore, reveals the initial panorama of the pandemic in this group. Moreover, it provides information that can help health workers and managers establish and implement care protocols for the pediatric population and their families.

CONCLUSION

The most frequently identified clinical status of the pediatric population that tested positive for SARS-CoV-2 included respiratory signs and symptoms, gastrointestinal symptoms and fever, and a significant number of asymptomatic patients.

Among the recommendations, identification activities, screening, and early treatment based on the epidemiological history of the pediatric population and family members, as well as isolation for more than fourteen days are highlighted.

This rapid review has some limitations. First, the a possible bias in the article selection process since consensus could not be established regarding collection carried out by a single researcher, although this fact characterizes the method. Second, the data limitations made it impossible to differentiate clinical manifestations in the different age groups of the pediatric population.

Further studies, such as randomized clinical trials or cohort studies, should be conducted to identify participation of the pediatric population in the transmission chain of COVID-19, especially regarding fecal-oral transmission of SARS-CoV-2, descriptions of clinical manifestations by pediatric age group, and routes of contamination in newborns and infants, with emphasis on vertical transmission and contamination by breast milk.

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Edited by

Associate editor:

Dagmar Elaine Kaiser

Editor-in-chief:

Maria da Graça Oliveira Crossetti

Publication Dates

  • Publication in this collection
    13 Sept 2021
  • Date of issue
    2021

History

  • Received
    03 June 2020
  • Accepted
    26 Feb 2021
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