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PONE-D-22-09133Clinical manifestations and disease severity of SARS-CoV-2 infection among infants in CanadaPLOS ONE

Dear Dr. Morris,

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PLOS ONE

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"JP reports grants to his institution from MedImmune, Merck, Sanofi Pasteur and AbbVie, and speaker fees from AbbVie and AstraZeneca, all outside of the submitted work. MS is supported via salary awards from the BC Children’s Hospital Foundation, the Canadian Child Health Clinician Scientist Program and the Michael Smith Foundation for Health Research. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments. PPPR has been co-investigator on an investigator-led project funded by Pfizer that is unrelated to this study. RP is a consultant for Verity Pharmaceuticals. SKM is co-principal investigator on an investigator-led grant from Pfizer, has served on an ad-hoc advisory boards for Pfizer and Sanofi Pasteur, and has received speaker fees from GlaxoSmithKline, all unrelated to this study. "

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

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

Reviewer #1: I Don't Know

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: This is a well written paper that provides a nice description of infants and their manifestations from COVID-19. I only have a two major thread of comments. The issue is the selection approach is not clear. The results from the selection approach are biased as well (connected to the patient selection approach), and this need to be clarified. These comments are specifically outlined below.

Abstract

1. Page 3, line 69: 37.5% admission clearly is biased if you are looking at this as all infants that acquired COVID-19. I think its important to make this clear throughout the paper. For instance on page 4, line 78, the authors state that most are mildly ill, but this doesn't compute with the 35% admission rate. The denominator of asymptomatic and not sick infants is not part of the study, so you need to be clear about this.

METHODS

2. Page 6, line 109: The CPSP needs to be clarified. Are these outpatient clinics? How does the hospital enrollment overlap or not?

3. Clarify that you did not include asymptomatic and those without significant disease from the CPSP, since it appears you did not. Or if I am not understanding this, please clarify.

4. Page 7, lines 136 - 139: It appears you have included 2800 outpatient practices and then also added 3 hospitals. Are the same participants included in both? If so, was that to obtain the outpatient + inpatient course together? Or are these separate? The three categories appears to me to be (1) CPSP, (2) either CPSP or hospital, (3) hospitals. I am not sure if this is right and it matters since it impacts your results.

RESULTS

5. Clarify the results with the selection criteria so its more clear how the results are connected (or not).

6. Page 15, lines 253 - 256 -- The criteria for hospitalization in young infants is pretty large -- fever in particular. While this is noted in the Conclusions, the results seem driven by this admission criteria and it should be pointed out sooner.

7. Page 15, line 257 -- Please also give the age in months since it seems odd to flip from one to the other.

8. Page 19, line 280: The fact that 78.7% of admitted children had mild disease shows the bias based on the selection approach and also the admission criteria, and should not be considered a finding of how sick these children are.

DISCUSSION

9. Page 23, second paragraph -- I do not believe the authors showed that COVID-19 is uncommon in children with this paper.

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Reviewer #1: No

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Clinical manifestations and disease severity of SARS-CoV-2 infection among infants in Canada

PONE-D-22-09133R1

Dear Dr. Morris,

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,

Everton Falcão de Oliveira, Ph.D

Academic Editor

PLOS ONE

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Reviewers' comments: