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      Severe Outcomes Associated With SARS-CoV-2 Infection in Children: A Systematic Review and Meta-Analysis

      systematic-review

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          To estimate the proportion of SARS-CoV-2 infected children experiencing hospitalization, intensive care unit (ICU) admission, severe outcomes, and death.

          Data Sources

          PubMed, Embase, and MedRxiv were searched for studies published between December 1, 2019 and May 28, 2021. References of relevant systematic reviews were also screened.

          Study Selection

          We included cohort or cross-sectional studies reporting on at least one outcome measure (i.e., hospitalization, ICU admission, severe outcomes, death) for ≥100 children ≤21 years old within 28 days of SARS-CoV-2 positivity; no language restrictions were applied.

          Data Extraction and Synthesis

          Two independent reviewers performed data extraction and risk of bias assessment. Estimates were pooled using random effects models. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

          Main Outcomes and Measures

          Percentage of SARS-CoV-2 positive children experiencing hospitalization, ICU admission, severe outcome, and death.

          Results

          118 studies representing 3,324,851 SARS-CoV-2 infected children from 68 countries were included. Community-based studies ( N = 48) reported that 3.3% (95%CI: 2.7–4.0%) of children were hospitalized, 0.3% (95%CI: 0.2–0.6%) were admitted to the ICU, 0.1% (95%CI: 0.0–2.2%) experienced a “severe” outcome and 0.02% (95%CI: 0.001–0.05%) died. Hospital-based screening studies ( N = 39) reported that 23.9% (95%CI: 19.0–29.2%) of children were hospitalized, 2.9% (95%CI: 2.1–3.8%) were admitted to the ICU, 1.3% (95%CI: 0.5–2.3%) experienced a severe outcome, and 0.2% (95%CI: 0.02–0.5%) died. Studies of hospitalized children ( N = 31) reported that 10.1% (95%CI: 6.1–14.9%) of children required ICU admission, 4.2% (95%CI: 0.0–13.8%) had a severe outcome and 1.1% (95%CI: 0.2–2.3%) died. Low risk of bias studies, those from high-income countries, and those reporting outcomes later in the pandemic presented lower estimates. However, studies reporting outcomes after May 31, 2020, compared to earlier publications, had higher proportions of hospitalized patients requiring ICU admission and experiencing severe outcomes.

          Conclusion and Relevance

          Among children tested positive for SARS-CoV-2, 3.3% were hospitalized, with rates being higher early in the pandemic. Severe outcomes, ICU admission and death were uncommon, however estimates vary by study population, pandemic timing, study risk of bias, and economic status of the country.

          Systematic Review Registration

          PROSPERO, identifier [CRD42021260164].

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          Most cited references44

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          A basic introduction to fixed-effect and random-effects models for meta-analysis.

          Michael R. Borenstein, Larry Hedges, Julian P.T. Higgins … (2010)
          There are two popular statistical models for meta-analysis, the fixed-effect model and the random-effects model. The fact that these two models employ similar sets of formulas to compute statistics, and sometimes yield similar estimates for the various parameters, may lead people to believe that the models are interchangeable. In fact, though, the models represent fundamentally different assumptions about the data. The selection of the appropriate model is important to ensure that the various statistics are estimated correctly. Additionally, and more fundamentally, the model serves to place the analysis in context. It provides a framework for the goals of the analysis as well as for the interpretation of the statistics. In this paper we explain the key assumptions of each model, and then outline the differences between the models. We conclude with a discussion of factors to consider when choosing between the two models. Copyright © 2010 John Wiley & Sons, Ltd. Copyright © 2010 John Wiley & Sons, Ltd.
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            The PRISMA 2020 statement: An updated guideline for reporting systematic reviews

            Matthew J L Page, Joanne E. Mckenzie, Patrick Bossuyt … (2021)
            Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.
            Article 0 comments Cited 1357 times – based on 0 reviews     Review now
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              Meta-analysis in clinical trials.

              R DerSimonian, N Laird (1986)
              This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
              Article 0 comments Cited 1068 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Pediatr
                Journal ID (iso-abbrev): Front Pediatr
                Journal ID (publisher-id): Front. Pediatr.
                Title: Frontiers in Pediatrics
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-2360
                Publication date (Electronic): 09 June 2022
                Publication date Collection: 2022
                Publication date PMC-release: 09 June 2022
                Volume: 10
                Electronic Location Identifier: 916655
                Affiliations
                [1] 1Schulich School of Medicine and Dentistry, Western University , London, ON, Canada
                [2] 2Section of Pediatric Emergency Medicine, Department of Pediatrics, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada
                [3] 3Department of Biological Sciences, University of Calgary , Calgary, AB, Canada
                [4] 4Health Sciences Library and Department of Community Health Sciences, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada
                [5] 5Sections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Cumming School of Medicine, University of Calgary , Calgary, AB, Canada
                Author notes

                Edited by: Silvia Bressan, University of Padua, Italy

                Reviewed by: Naïm Ouldali, Hôpital Robert Debré, France; Stephen Aronoff, Temple University, United States

                *Correspondence: Stephen B. Freedman, stephen.freedman@ 123456albertahealthservices.ca

                †These authors share senior authorship

                This article was submitted to General Pediatrics and Pediatric Emergency Care, a section of the journal Frontiers in Pediatrics

                Article
                DOI: 10.3389/fped.2022.916655
                PMC ID: 9218576
                PubMed ID: 35757137
                SO-VID: 57b2074c-9a49-459d-aa00-5b607ee71b91
                Copyright © Copyright © 2022 Sumner, Kanngiesser, Lotfali-Khani, Lodha, Lorenzetti, Funk and Freedman.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 09 April 2022
                Date accepted : 18 May 2022
                Page count
                Figures: 8, Tables: 2, Equations: 0, References: 49, Pages: 14, Words: 6476
                Categories
                Subject: Pediatrics
                Subject: Systematic Review

                Keywords: covid-19,meta-analysis,sars-cov-2,severity,outcomes,children
                Data availability:
                Keywords: covid-19, meta-analysis, sars-cov-2, severity, outcomes, children

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