PONE-D-24-35787Severity of acute SARS-CoV-2 infection and risk of new-onset autoimmune disease: A RECOVER initiative study in nationwide U.S. cohortsPLOS ONE

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PLOS 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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

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:  The study "Severity of Acute SARS-CoV-2 Infection and Risk of New-Onset Autoimmune Disease" investigates how COVID-19 severity influences the risk of developing autoimmune diseases. The results indicated that severe COVID-19 cases had a significantly higher risk of new-onset autoimmune disease. In adults, diseases like inflammatory arthritis and Sjögren’s syndrome were common, while in children, conditions such as type 1 diabetes and hematological autoimmune diseases were observed. The highest severity category, "hospitalized with ventilation," was associated with a particularly elevated risk, underscoring a dose-response relationship between COVID-19 severity and autoimmune disease development.

Overall, this article well designed and written. I only have some MINOR comments:

1. Introduction Background. The introduction provides a solid foundation by discussing the potential link between viral infections and autoimmunity. To enhance this section, a brief overview of existing literature on COVID-19's role in triggering autoimmune responses would contextualize the study's significance. This addition would underscore the relevance of investigating the association between COVID-19 severity and subsequent autoimmune disease onset.

2. Justification of Disease Classification. The study defines new-onset autoimmune disease based on the presence of two new ICD codes within 30 days. While this criterion is practical, it may not fully account for transient inflammatory responses that do not culminate in chronic autoimmune conditions. Providing a rationale for this definition or acknowledging it as a limitation would strengthen the study's methodological transparency.

3. Adjustment for Covariates. The multivariable models adjust for several baseline characteristics, which is commendable. However, the discussion could be enriched by exploring whether factors such as body mass index (BMI), socioeconomic status, or ethnicity might confound the observed association between COVID-19 severity and autoimmune risk. Addressing these variables would provide a more comprehensive understanding of potential confounders.

4. Inclusion of Vaccination Status. Considering the role of COVID-19 vaccination in potentially mitigating autoimmune risk, it would be pertinent to mention whether participants' vaccination statuses were considered or excluded. This information would enhance the study's relevance to current public health considerations.

5. Discussion. Suggest adding more discussion on literatures and mechanism and cite relevant references. eg. 6. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1756-185X.14963; https://onlinelibrary.wiley.com/doi/epdf/10.1111/1756-185X.14766

Reviewer #2:  This study presents interesting findings, but there are a few concerns that need to be addressed.

1. The term COVID-19 infection is inaccurate. It is recommended to revise it to SARS-CoV-2 infection for precision.

2. Have you considered addressing reinfection in your analysis? Please clarify.

3. Regarding the phrase World Health Organization COVID-19 severity category for adults, while it is clear that you are using WHO guidelines, additional details are needed. Specifically, what codes were employed, and how was the time frame defined?

4. For the PEDSnet acute COVID-19 illness severity classification system for children, please provide more detailed information regarding its criteria and application.

5. Include the follow-up duration for each cohort used in the study.

6. The resolution of the figures is too low, rendering them uninterpretable and not informative. Kindly provide high-resolution versions of all figures.

7. It is suggested to refer to PMID: 38437702, not only for discussion but also as a reference for expressions such as SARS-CoV-2 infection.

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Reviewer #1: No

Reviewer #2: No

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Severity of acute SARS-CoV-2 infection and risk of new-onset autoimmune disease: A RECOVER initiative study in nationwide U.S. cohorts

PONE-D-24-35787R1

Dear Dr. Wuller,

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,

Dong Keon Yon, MD, FACAAI, FAAAAI

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

This is an excellent paper!

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

**********

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: All previous comments were answered.

I have no further comment. No additional comments for the author, including concerns about dual publication, research ethics, or publication ethics.

Reviewer #2: (No Response)

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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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