-->PONE-D-26-10551-->-->Longitudinal full blood count dynamics in immunologically naïve individuals with mild COVID-19: a prospective community cohort study-->-->PLOS One

Dear Dr. Hakki,

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Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: 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: This is a prospective community cohort study evaluating the full blood count dynamics in immunologically naïve individuals with mild COVID-19 in the UK.

Please see my recommendations below

Abstract

1. Sentence is too long. “Over 30% of cases exhibited transient, clinically defined neutropenia (mean (95% CI): First PCR-Positive (FP) 2.47x109/L (2.26-2.68) vs convalescence 3.34 x109/L (2.98-

3.7); p=0.0013), while over 20% exhibited lymphopenia (FP 1.38x109/L (1.28-1.48) vs

convalescence 1.79x109/L (1.79-2.01); p=0.0013).’’

2. The conclusion of ‘well-characterised’ should be revised as only 30% showed neutropenia & 20% had lymphopenia

Materials & method

What were the inclusion & exclusion criteria?

Please define clinically-relevant neutropenia

Results & discussion

It would be good to separate the results & discussion parts for clearer flow of the manuscript

Line 132-135 – what were the findings of majority of the patients given only 30% had transient neutropenia & 20% lymphopenia?

Line 144-145 – what was the severity of Covid-19 infection in these patients?

Lines 152-155 – the p values are similar. Please recheck the results

Table S1

Ethnicity . to remove unknown 0 (0%)

What is the relevance of Fig S1? Are all results at all time-points lumped together?

Fig 2. Why was mean & 95% CI used in the figure? At pp interval, the number of cases are consistently less than 30? Would median be more appropriate?

Reviewer #2: The authors have made a good attempt at trying to prospectively study the Longitudinal full blood count dynamics in immunologically naïve individuals with mild COVID-19, but i have the following comments:

It is important to state clearly without any ambiguity in the methodology how the heterogeneity in the sampling timepoints were handled.It is to be noted that this has to be reported under methodology and not under results and discussion.

It is reported in the abstract that sampling started at the first PCR positivity,but later reported that prepositive samples were collected.The actual time of sampling initiation have to be reported in the abstract.

The discussion of the result focussed on FP and convalescence, no picture was given about what happened between those two periods.

The authors have to state whether the 65 individuals were removed from 93 or from 158 (93+65) during Patient recruitment.

Reviewer #3: The main concerns with the current mansucript is the aging of the dataset. This data was collected between 2020 and 2021 and is only submitted for publication in 2026. This creates a question around the current value of the mansuscript. Further to this, the relative small sample size in a proposed longitudinal study of this nature is a limitation. Further to this, in my opinion to classify the study as longitudinal, but only measuring 30 days is questionable. Counts might recover significantly in a longer follow-up time. The major concern though is referring to haematological profiling but only assessing full blood counts. It would have been recommended to assess the coagulation parameters.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Attachments

Attachment

Submitted filename: rv 1.docx

Full blood count dynamics in immunologically naïve individuals with mild COVID-19: a prospective community cohort study

PONE-D-26-10551R1

Dear Dr. Hakki,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

José Ramos-Castañeda, M.Sc., Ph.D

Academic Editor

PLOS One

Additional Editor Comments:

After giving the matter careful consideration, and bearing in mind that Reviewer 4 did not in fact raise any objections to the manuscript itself, but rather offered a general opinion on the manuscript, and, finally, given that the arguments put forward by the three reviewers of the first version have been satisfactorily addressed, I have decided not to forward Reviewer 4’s comments and to accept the manuscript for publication.

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 #2: All comments have been addressed

Reviewer #4: 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 #2: Yes

Reviewer #4: No

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

Reviewer #2: Yes

Reviewer #4: No

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-->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 #2: Yes

Reviewer #4: 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 #2: Yes

Reviewer #4: 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 #2: The authors have adequately addressed the comments made at the initial review. The comment dwelt mainly on the sampling method, which the authors have made more explicit, hence to account for heterogeneity in the day of enrolment relative to the day of acquiring detectable infection, sampling timepoints were realigned relative to the day of the first PCR-positive study sample “Pre-positive” (PP) refers to blood samples taken prior to the case testing PCR-positive, whilst “First PCR-positive” (F refers to the blood samples taken when the case first tested PCR-positive in

the study. “FP+7” and “FP+14” refers to samples taken seven- and fourteen-days post-FP respectively.

Reviewer #4: 1. Introduction: Authors could be introduce major information about pathophysiology and biological explication why could COVID affect blood counts?

2. Methodology: That is curious you evaluated patients and cell blood counts after to take of exam, but for me could be more relevant include count cell since starting symptoms, because of an information bias. Additionally you don't mention size necessary for this paper.

3. Results and conclusion: It is interesting your results but I don't understand what is clinical relevance to take of decisions with this results, how this results could be help to apply in daily practice.

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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.

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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 #2: No

Reviewer #4: No

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