PONE-D-22-12572Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19 infection: a cohort studyPLOS ONE

Dear Dr. Stavem,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

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Tai-Heng Chen, M.D.

Academic Editor

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: No

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 authors investigated the cognitive function for non-hospitalized patients with PCR-confirmed COVID-19 patients. They longitudinally followed them.

At median 11 (range 8–13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001).

At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

I will raise some concerns before publication.

Major

#1

Why did not the authors perform cognitive testing for dyspnea group? The authors hypothesized that the cognitive sequelae were associated with hypoxia. Then, dyspnea group should be conducted cognitive testing.

Could you elaborate on “Because of risk of attrition”?

#2

As the authors pointed out, the repone rate was low. Selection bias should be considered.

Are there any differences between response and non-response to questionnaire of survey 1?

If any, discuss it. And are there any differences between response and non-response to CANTAB of survey 2? If any, discuss it.

Minor

#3

In Result, Sample

“191 of these patients refused further follow-up” should be “19 of these patients refused further follow-up”.

#4

Please mention the COVID-19 infectious situation, such as local infections prevalence and mutation of prevalent SARS-CoV-2.

Over all, the paragraph division is bad and it is difficult to read.

Reviewer #2: Overall statement

This study aims to evaluate the effect of Covid-19 infection on cognitive function in non-hospitalized patients. The researchers found that late after a Covid-19 infection, non-hospitalized patients showed only slightly lower cognitive test scores. The research question is clearly outlined. The authors used a detailed cognitive test battery. The results seem to be valid and reliable. In my opinion the sample size is limited for a population based study.

Strengths and impact

This is a longitudinal study that includes evaluations with a good quality cognitive test battery (CANTAB). This battery evaluates many cognitive domains, especially executive functions. The title of the study is informative. The study aim is interesting since they measured the cognitive effects after a Covid-19 infection in a non-hospitalized group with low comorbidity scores. The references at the end of the text are up to date. The current knowledge about the topic are given in detail. Statistical methodology seems to be nice (using Z scores). The manuscript is generally well written (especially discussion).

Minor weaknesses

1. Even if they designed a longitudinal study, the reserchers very found mild differences in cognitive scores (%4-14). Since this is a cognitive study. The results must be discussed further in relation to participant age, educational status and comorbid conditions. It may be possible to find significant cognitive differences in an elderly population with a larger sample size.

2. The introduction is well written. The author wrote that they aimed to determine the prevalence of cognitive deficits 8-13 months after Covid-19 infection. The author must explain the importance/meaning of this time interval (8-13 months) since they wrote it in the study aim and the title.

3. Did any of the patients have CT documented pulmonary Covid disease? The Figure legends are missing.

4. The researcher divided the patients with a Covid-19 history into 3 groups according to their symptoms (fatigue, dyspnea & fatigue, no dyspnea or fatigue). I think that this classification makes the study a little bit confusing. If I were to do a patient classification for non-hospitalized Covid-19 patients I would divide them into 2 groups such as; asymptomatic/mild symptomatic and symptomatic (including dyspnea and apparent fever). Maybe if they made 2 patient groups with a different methodology, they could have included dyspnea only patients and the remaining asymptomatic patients to increase the sample size.

5. Table 1. is informative. Table 3. is easy to understand and definitive. The regression analysis did not reveal any significance except patient age (Table 5.). The author may want to make a subgroup analysis in older participants to see which cognitive domains were effected after an acute Covid-19 infection.

6. In the results/sample section the number of patients participated in CANTAB was given as 233. In Table 2. the number seems to be 234?

7. Even if the author made adjustments for possible confounders, there may be other confounders not taken into account. There is no control group as the author mentioned. Therefore, it would be better if the author writes some more possible limitations.

Major weaknesses

1. In my opinion the sample size is limited for a population based study.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-22-12572R1Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19 infection: a cohort studyPLOS ONE

Dear Dr. Stavem,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 26 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Tai-Heng Chen, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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: N/A

**********

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: No

Reviewer #2: Yes

**********

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: The manuscripts were well revised.

All my concerne were satisfied.

I raise one addition comments.

Minor

The title should be revised,

Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19

infection: a cohort study

===>

Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19

infection: a cohort study in Norway.

Reviewer #2: This is the revised manuscript of a study that aimed to evaluate the effect of Covid-19 infection on cognitive function in non-hospitalized patients. In my opinion the revisions are OK. Author responses are satisfactory.

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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

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19 infection: a cohort study in Norway

PONE-D-22-12572R2

Dear Dr. Stavem,

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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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Tai-Heng Chen, M.D.

Academic Editor

PLOS ONE

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

**********

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

**********

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

Reviewer #1: 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

**********

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

**********

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 title has been changed as a comment.

All my concerns were satisfied.

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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

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