REVIEW PROTOCOL

Conditions associated with the worsening of COVID-19 in children and adolescents: scoping review protocol

Larissa Silva Bergantini1, Roberta Rossa1, Bianca Machado Cruz Shibukawa1, Marcela Demitto Furtado1, Bruna Alves de Jesus Vieira1, Angélica Yukari Takemoto1, Ieda Harumi Higarashi1, Sueli Mutsumi Tsukuda Ichisato1

1 State University of Maringá, Paraná, Brazil

ABSTRACT

Objective: To map the available scientific knowledge about the conditions associated with the worsening of the COVID-19 situation in children and adolescents. Method: This is a protocol of a scoping review based on the Joanna Briggs Institute methodology. The following databases were chosen: MEDLINE via PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), LILACS via Virtual Health Library (BVS), and Google Scholar. Two independent reviewers will carry out the search. The retrieval of references will take place in three steps according to the Joanna Briggs Institute recommendations. Medical Subject Headings (MeSH) descriptors and Health Sciences Descriptors (DeCS) will be used. The mapping tool suggested by the adopted reference will be used to extract the results. The results will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR).

Descriptors: COVID-19; Child; Risk Factors.

INTRODUCTION

On March 11, 2020, the World Health Organization (WHO) announced the Coronavirus disease 2019 (COVID-19) pandemic state(1). The first cases of the hitherto unknown pathology were reported in December 2019, in the Chinese city of Wuhan, in the province of Hubei, and a new type of coronavirus was identified as the etiological agent of the infection(2). The virus that triggers pneumonia of atypical presentation observed in patients was initially titled 2019-nCoV; then, in mid-February 2020, it was renamed by the International Committee on Taxonomy of Viruses as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)(3).

The COVID-19 pandemic is one of the greatest and most serious public health challenges at a global level that has punctuated the history of humanity(4). The total number of cases accumulated in the world until this date, February 10, 2022, exceeds the mark of 400 million people infected and more than 5.7 million deaths(5).

When it comes to the pediatric population, the clinical spectrum of COVID-19 can range from asymptomatic cases to the development of severe acute respiratory syndrome(6). Furthermore, the main symptoms of the pathology observed in children include fever, cough, and nasal symptoms such as nasal congestion and diarrhea, nausea, or vomiting, among others(7).

The disease seems to be less frequent among children, and, in general, it appears to result in less severe manifestations than in adult patients(8).

Several hypotheses have been reported in the scientific literature, aiming to substantiate the reasons for the lower severity of COVID-19 among pediatric patients. Among the possible justifications are the periodic exposure of children to viral infections and the relevant role of the angiotensin-converting enzyme 2, whose receptor is the target of SARS-CoV-2 binding, allowing the entry of the virus into the cells(9).

Although the prognosis of COVID-19 in this population is more favorable, children are susceptible to the pathology(10) and to severe conditions that require hospitalization in the Intensive Care Unit (ICU), use of mechanical ventilation, and death(11).

Another highlighted aspect is that children exposed to SARS-CoV-2 can develop the so-called Pediatric Multisystem Inflammatory Syndrome (PIMS). The condition, considered rare, has clinical characteristics similar to Kawasaki disease (KD), and some common signs and symptoms include fever, mucocutaneous findings, such as rash and edema of the extremities, gastrointestinal symptoms, myocardial dysfunction, and shock(12).

A study that included 20,714 patients aged 18 years or younger affected by COVID-19 found that 11.7% required hospitalization, 3.6% were admitted to the ICU, and 0.8% received invasive mechanical ventilation(11). Another study, carried out in six pediatric hospitals in the United States, found that 14.5% of patients hospitalized due to the disease required invasive mechanical ventilation, 29.5% were treated in the ICU, and 1.5% died. Among the 915 children involved, 2.7% were diagnosed with PIMS(13).

Finally, it should be noted that the possibility of complications from COVID-19, such as PIMS and long-term COVID-19, the heightened vulnerability of children with comorbidities, the emergence of new variants of SARS-CoV-2, and other factors triggered the discussion about vaccination for these patients. Analyzes have indicated vaccines' efficacy, safety, and immunogenicity against COVID-19 in this population and, based on the results from these analyses, health authorities, at a global level, extended immunization to adolescents and, later, to children(14).

A previous search in two relevant health databases (MEDLINE via PubMed and Scopus) identified several literature reviews on COVID-19 in children. However, we found no reviews addressing the possible conditions related to the deterioration of the clinical status of children and adolescents affected by the pathology.

Thus, it is important to synthesize the existing knowledge regarding the potential factors that induced some children and adolescents to develop severe COVID-19 or critical conditions since research in this area is still incipient(15). The present research aims to map the available scientific knowledge about the conditions associated with the worsening of the COVID-19 situation in children and adolescents.

METHOD

This study is a protocol for a scoping review based on the Joanna Briggs Institute (JBI) methodology(16), and we will follow the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). The scoping review is a suitable method for mapping the evidence available in the literature, and it is also viable to investigate emerging areas of knowledge, such as COVID-19(16-17). This research protocol was registered in the Open Science Framework (OSF), with registration no. 10.17605/OSF.IO/328FR.

The research question developed to guide the review was: What scientific knowledge is available on the conditions related to the worsening of COVID-19 in children and adolescents? The mnemonic PCC (Population, Concept, and Context) was used as follows: "P": children and adolescents; "C": conditions related to the worsening of COVID-19; and "C": the COVID-19 pandemic.

Individuals up to 10 years of age were considered children, and adolescents were those aged between 10 and 19 years, in line with the WHO classification(18-19). Furthermore, due to the heterogeneity of criteria for classifying the severity of the disease available in the literature, the following indicators of COVID-19 worsening were determined: the need for hospitalization, ICU admission, and demand for ventilatory support.

The following databases were chosen: MEDLINE via PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), LILACS via Virtual Health Library (BVS), and Google Scholar. In addition, articles published from December 2019 onwards (date of the advent of COVID-19 cases) will be included, in any language, since they are available in full format and address children and adolescents with confirmed SARS-CoV-2 infection. Suppose the study simultaneously encompasses adult individuals (or other populations, such as older adults, pregnant women, etc.) besides children and adolescents. In that case, it will only be integrated into the review if the results are presented separately, allowing the differentiation of data concerning children and adolescents. In order to map the available knowledge extensively, restrictions will not be established regarding the study design as long as the research deals with the conditions associated with COVID-19 worsening. References that do not answer the research question or the proposed objective will be excluded.

Two independent reviewers will carry out the search. The retrieval of references will occur in three steps, according to the recommendations of the JBI(16). The first step concerns a limited initial search in relevant databases and the analysis of titles, abstracts, and keywords. The second phase corresponds to a search in all the chosen databases, using the descriptors and keywords identified in full. In the last step, the reference list of articles chosen for review will be used to detect additional studies.

First, the two reviewers will read the titles and abstracts of the articles for pre-selection, and then the full texts will be screened. In case of divergences, and if there is no consensus, a third reviewer will decide whether or not to select the study.

Regarding the search strategy, the Medical Subject Headings (MeSH) and the Health Sciences Descriptors (DeCS) will be used in addition to uncontrolled descriptors, helping retrieve relevant articles. The following descriptors were initially defined: "children", "adolescent", "coronavirus infections", "COVID-19", "SARS-CoV-2", "intensive care units", "hospitalization", and "artificial respiration". The Boolean operators AND and OR will be used for the advanced search. The initial search strategy that will be applied to retrieve articles from MEDLINE through PubMed is described in Figure 1. It is noteworthy that the filters for "full text" and time (studies published from 2019) are included in the strategy.

Figure 1 - Search strategy to retrieve articles from MEDLINE via PubMed. Maringá, PR, Brazil

Source: Elaborated by the authors, 2022.

The mapping tool suggested by the JBI(16) will be used to extract the results. Articles selected for review will be stored and organized using the Mendeley Desktop® reference manager. Since scoping reviews aim not to generate critically evaluated and condensed answers, the methodological limitations, and risk of bias of the incorporated articles will not be assessed(20). The results will be presented according to the guidelines of the PRISMA-ScR checklist. Finally, the study is exempt from review by an Ethics Committee since it is a literature review.

CONFLICT OF INTEREST

The authors have declared that there is no conflict of interest.

FUNDING

This study was financed in part by the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES) – Brazil – Finance Code 001.

REFERENCES

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Submission: 05/31/2021

Approved: 03/25/2022