PONE-D-24-06176A systematic review of post COVID-19 condition in children and adolescents: Gap in evidence from low and -middle-income countries and the impact of SARS-COV-2 variantsPLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: A systematic review of post-COVID-19 symptoms in children and adolescents, focusing on low- and middle-income countries (LMICs), analyzed 40 studies with 825,849 participants. Most studies involved adolescents, with limited data on young children. Only one study from an LMIC was identified, involving 58 participants. The studies varied in their definitions and durations of post-COVID-19 conditions, complicating comparisons. Prevalence ranged from 1.8% to 70%, with notable heterogeneity and reliance on self-reported symptoms. Fatigue, headache, and respiratory symptoms were the most common. The review highlighted the need for more data from LMICs and young children.

Although this study provided interesting insights, I recommend further revisions to refine the manuscript:

Recent studies have shown the possible persistence of long COVID for 2 years in the general population (DOI: 10.1016/j.jinf.2023.12.004). However, the meta-analysis data reported in this study is only limited to the adult population. It would be important to emphasize the need for a more in-depth analysis looking at the prevalence of long COVID symptoms in the pediatric age group and how these symptoms compare with the adult population.

Kindly include a supplementary section detailing the search strategy and the outcome of the meshed search terms for every journal database used.

Please include a PICO statement as well as the PRISMA checklist.

Kindly include the rationale for why a meta-analysis was not performed in this study. You can include this statement in the methods section.

Did the studies included in the systematic review undergo quality assessment, such as using the Newcastle-Ottawa scale, QUIPS, etc.? If not, please include a quality check for all the studies to assess the risk of bias.

This systematic review lacks in-depth analysis. It is important to report the pooled demographics of the children and adolescents included in this review.

Were there control groups included in the study? For example, children or adolescents who are either healthy or those who succumbed to an acute infection but did not develop long COVID?

What were the limitations of the present study? What are the gaps that need to be addressed in long COVID research involving these age groups?

There are many theories contributing to the development of long COVID. I think it is important to highlight these studies, which include the possible persistence of SARS-CoV-2 RNA (DOI: 10.1515/cclm-2024-0036), excessive inflammatory response, and even the generation and persistence of autoantibodies (DOI: 10.3389/fimmu.2024.1428645).

It is also important to highlight the several factors that can influence the severity and risk of developing long COVID, including vaccination prior to an acute infection (DOI: 10.1016/j.eclinm.2022.101624), administration of antivirals during the acute phase of SARS-CoV-2 infection (DOI: 10.1007/s15010-023-02154-0), and demographics like sex and certain comorbidities (DOI: 10.3390/jcm11247314), as well as the infecting SARS-CoV-2 variant (DOI: 10.3390/v14122629).

Reviewer #2: The manuscript has shown a good work of a scientific article, however, I noticed that there is still room for improvement, which can be found in the file I attached in this section. Please revise the manuscript accordingly, thank you!

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PONE-D-24-06176-IR.docx

A systematic review of post COVID-19 condition in children and adolescents: Gap in evidence from low and -middle-income countries and the impact of SARS-COV-2 variants

PONE-D-24-06176R1

Dear Dr. Putri,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Muhammad Iqhrammullah, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript has been extensively revised and is now acceptable for publication. Congratulations to the authors.

Reviewer #2: Thank you for addressing my concerns! Now the manuscript has improved a lot, especially in terms of its quality and readability. I would suggest it for publication.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #2: No

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