Peer Review History

Original SubmissionSeptember 22, 2020
Decision Letter - Wen-Jun Tu, Editor

PONE-D-20-29228

Impact of COVID-19 on Hospital Admission of Acute Stroke patients in Bangladesh

PLOS ONE

Dear Dr. Hasan,

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 Dec 04 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Wen-Jun Tu

Academic Editor

PLOS ONE

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[The author(s) received no specific funding for this work.].   

We note that one or more of the authors are employed by a commercial company: BioTED

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If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement.

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3. Please include a separate caption for each figure in your manuscript.

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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

Reviewer #3: No

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

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

Reviewer #3: Yes

**********

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: No

Reviewer #3: Yes

**********

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: 1. Need to have the manuscript reviewed by a science/technical writer would be useful as the discussion section has a lot of verbiage.

2. There are typographical errors which can be addressed by spell check

Reviewer #2: The manuscript requires some grammatical assistance.

The overall information regarding stroke admissions pre and during COVID is of value and interest to the scientific and medical community. Although limited application as only one country- still important.

Would like the authors to comment whether these individuals who didn't come to hospital- what do the authors anticipate the long term effects of people not coming to the hospital with stroke? Was there a rise in stroke related deaths? Do the authors know this?

Reviewer #3: While the concept is interesting, the epidemiology methods are not rigorous and the study has not been performed in a manner that will actually answer the question. Currently, total infection rates are not known, comparisons across different time periods may not be valid as SARS-CoV-2 could have been present well before March, and the pathophysiology of COVID-19 related stroke is not well known yet, so it's not clear how long after an infection that a stroke may develop.

**********

6. 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

Reviewer #3: 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.

Revision 1
Decision Letter - Wen-Jun Tu, Editor

PONE-D-20-29228R1

Impact of COVID-19 on hospital admission of acute stroke patients in Bangladesh

PLOS ONE

Dear Dr. Hasan,

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.

==============================

ACADEMIC EDITOR:

1. In order to provide a more complete information to our readers on the topic, we would like to emphasize the importance to cross referencing very recent material on the same topic published in "PLoS ONE ".

2. Added “Cao, J., Tu, W. J., Cheng, W., Yu, L., Liu, Y. K., Hu, X., & Liu, Q. (2020). Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China. Clinical Infectious Diseases.”in revision text. 

==============================

Please submit your revised manuscript by Jan 29 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Wen-Jun Tu

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

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

Reviewer #3: (No Response)

**********

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: (No Response)

Reviewer #3: (No Response)

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

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

Reviewer #3: (No Response)

**********

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

Reviewer #3: (No Response)

**********

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: They have tried to improve the submitted manuscript grammatically, in my humble opinion it could have improved further.

Reviewer #2: No further comments for the authors of this manuscript. They addressed all of my concerns in the revised document.

Reviewer #3: Thank you for your attention to all the reviewers's comments and questions. I believe that the authors have addressed all comments to their abilities.

**********

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

Reviewer #3: 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.

Response to Reviewers

Reviewer #1:

Comment 1: Need to have the manuscript reviewed by a science/technical writer would be useful as the discussion section has a lot of verbiage.

Authors’ response: We thank the reviewer for his/her advice. We have now rewritten the discussion section to remove the verbiage as much as possible and have the manuscript reviewed by a professional technical writer.

Comment 2: There are typographical errors which can be addressed by spell check

Authors’ response: We apologize for overlooking the errors. We have now corrected the typographical errors we have identified.

Reviewer #2:

Comments: The manuscript requires some grammatical assistance.

The overall information regarding stroke admissions pre and during COVID is of value and interest to the scientific and medical community. Although limited application as only one country- still important. Would like the authors to comment whether these individuals who didn't come to hospital- what do the authors anticipate the long-term effects of people not coming to the hospital with stroke? Was there a rise in stroke related deaths? Do the authors know this?

Authors’ response: We thank the reviewer for this important suggestion. We have identified and corrected some grammatical mistakes after careful revision of the manuscript, and further had it reviewed by a professional proof reader.

Like the reviewer we were also curious about the fate of the individuals who possibly failed to turn up into hospitals for stroke treatment during the pandemic. To our knowledge, no records of these individual were available nor any information on them including mortality were collected. Unfortunately, therefore, we are not in a position to confirm any definitive consequence of missing timely hospital treatment. However, we speculate fatalities or detrimental long-term effects including impaired speech and paralysis for these individuals.

We have now included the following statement in the Discussion section:

“While deaths and detrimental long-term effects including impaired speech, paralysis of limbs and restricted physical abilities were speculated for missing timely hospital treatment, the extent of such consequences could not be confirmed due to unavailability of required data.”

Reviewer #3:

Comments: While the concept is interesting, the epidemiology methods are not rigorous and the study has not been performed in a manner that will actually answer the question. Currently, total infection rates are not known, comparisons across different time periods may not be valid as SARS-CoV-2 could have been present well before March, and the pathophysiology of COVID-19 related stroke is not well known yet, so it's not clear how long after an infection that a stroke may develop.

Authors’ response: We thank the reviewer for the careful observation and comment.

In response, we first we want to make it clear that the only question investigated in this paper is whether the stroke admission data supported the general fear that there was a rise in stroke cases during the time (after March 2020), which saw a surge in COVID-19 infections in Bangladesh. The fact that an incidence of stroke requires special medical treatment available only at stroke caring facilities/hospitals it is reasonable to expect that admission data will fairly reflect major changes in the number of new stroke cases. It is evident from the data and analysis that, contrary to the fear, there is a significant drop in stroke admissions during the wide-spread outbreak of the virus compared to the earlier period.

We understand the reviewer’s concern regarding the validity of the study design for answering the research question. While we know that a prospective study following hospital admitted COVID-19 patients up to the development of any stroke would be a much better design, retrospective studies have been used to investigate similar questions (e.g., Hoyer et al., 2020). We, however, cited comparing just six months of the same year 2020 as a possible limitation of our study. We also acknowledged that comparison across the same periods of the COVID-19-year of 2020 and an earlier year, as conducted in Hoyer et al. (2020), would have been a fairer comparison. Nonetheless, we could not pursue this due to the unavailability of the required longer time series from a relatively young stroke unit and clearly pointed out this limitation in the manuscript.

We want to further argue that the retrospective comparison of admissions before and including March (our pre-COVID period) and the period thereafter (our COVID period) is a reasonable, if not ideal, comparison. First, while the reviewer is correct in pointing out the possibility of the presence of SARS-COV-2 in Bangladesh before March, we have strong reasons to believe that the total number of infections prior to March was much lower than that after March since when official statistics reported a rapid increase in the number of infections in the country.

Second, while it is true that the pathophysiology of COVID-19 related stroke is still not perfectly known, we found a fair amount of evidence (as cited in the paper) which links COVID-19 to coagulopathy causing venous and arterial thrombosis (Oxley et al., 2020, Beyrouti et al., 2020) which are major risk factors for stroke. A recent study further found significant association between the severity of COVID-19 and increased risk of acute stroke (Siepman et al., 2020).

Most importantly, although the exact duration of development of stroke in COVID-19 patients may not be definitely known, the study by Beyrouti et al. (2020) found that five out of six patients admitted with both COVID-19 and stroke actually developed ischaemic stroke within 8-24 days after COVID-19 symptom onset. Since we compared 3-month (90-day) average admissions before and after March we reasonably expected a significant number of new developments of stroke to occur during the latter period of higher rates of infection and get reflected accordingly in the admission data during that period. This made us believe that the comparisons we made are fair for testing our hypothesis. The fact that the empirical evidence goes in the opposite direction of the hypothesis only made it even more interesting.

We have already cited the references used in making our arguments in the original manuscript and included further evidence.

References:

1. Hoyer, C., Ebert, A., Huttner, H.B., Puetz, V., Kallmünzer, B., Barlinn, K., Haverkamp, C., Harloff, A., Brich, J., Platten, M. and Szabo, K., 2020. Acute Stroke in Times of the COVID-19 Pandemic: A Multicenter Study. Stroke, pp.STROKEAHA-120.

2. Oxley, T.J., Mocco, J., Majidi, S., Kellner, C.P., Shoirah, H., Singh, I.P., De Leacy, R.A., Shigematsu, T., Ladner, T.R., Yaeger, K.A. and Skliut, M., 2020. Large-vessel stroke as a presenting feature of Covid-19 in the young. New England Journal of Medicine, 382(20), p.e60.

3. Beyrouti, R., Adams, M.E., Benjamin, L., Cohen, H., Farmer, S.F., Goh, Y.Y., Humphries, F., Jäger, H.R., Losseff, N.A., Perry, R.J. and Shah, S., 2020. Characteristics of ischaemic stroke associated with COVID-19. Journal of Neurology, Neurosurgery & Psychiatry.

4. Siepmann, T., Sedghi, A., Simon, E., Winzer, S., Barlinn, J., de With, K., Mirow, L., Wolz, M., Gruenewald, T., Schroettner, P. and von Bonin, S., 2020. Increased risk of acute stroke among patients with severe COVID‐19: a multicenter study and meta‐analysis. European Journal of Neurology.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Revision 2
Decision Letter - Wen-Jun Tu, Editor

Impact of COVID-19 on hospital admission of acute stroke patients in Bangladesh

PONE-D-20-29228R2

Dear Dr. Hasan,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Wen-Jun Tu

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Response to the Academic Editor:

Comment 1: In order to provide a more complete information to our readers on the topic, we would like to emphasize the importance to cross referencing very recent material on the same topic published in "PLoS ONE ".

Authors’ response: We would like to thank the academic editor for the comment. We have added relevant points in the “Introduction and Discussion” section from the following three related articles published very recently in PLos ONE. The articles are cited in text and listed in the reference according to the following serial numbers:

2. Campiglio L, Priori A. Neurological symptom in acute COVID-19 infected patients: A survey among Italian physicians. PLoS One. 2020 Sep; 15 (9): e0238159.

5. Jillella DV, Janocko NJ, Nahab F, Benameur K, Greene JG, Write WL, et al. Ischemic stroke in COVID 19: An urgent need for identification and management. PLoS One. 2020 Sep; 15 (9): e0239443.

23. Stöhr E, Aksoy A, Campbell M, Al Zaidi M, Öztürk C, Vorloeper J, et al. Hospital admissions during COVID-19 lock-down in Germany: Differences in discretionary and unavoidable cardiovascular events. PLoS One. 2020; 15 (11): e0242653.

Comment 2: Added “Cao, J., Tu, W. J., Cheng, W., Yu, L., Liu, Y. K., Hu, X., & Liu, Q. (2020). Clinical features and short-term outcomes of 102 patients with corona virus disease 2019 in Wuhan, China. Clinical Infectious Diseases.” in revision text.

Authors’ response: We would like to thank the academic editor for suggesting this important and timely article on clinical presentation and outcome of COVID patients. We have added a few more words in the introduction and cited the article as a reference in the revised text.

Comment 3: Resubmit figures.

Authors’ response: We have uploaded the files to PACE digital diagnostic tool to covert to appropriate tif format and made the adjustments as per the requirement of the journal.

Response to the Reviewers’ comments:

Reviewer 1:

Comment: They have tried to improve the submitted manuscript grammatically, in my humble opinion it could have improved further.

Authors’ response: We would like to thank the reviewer for the comment. We can ensure that we have tried to improve the grammar of the manuscript to the best of our abilities. We are hopeful that it now meets the required standard of the journal.

Reviewer 2:

Comment: No further comments for the authors of this manuscript. They addressed all of my concerns in the revised document.

Authors’ response: We thank the reviewer for his/her important comments raised previously and we are happy to learn that we managed to address all his/her concerns.

Reviewer 3:

Comment: Thank you for your attention to all the reviewers' comments and questions. I believe that the authors have addressed all comments to their abilities.

Authors’ response: We thank all the reviewers for their comments on the original manuscript. We would like to ensure that we tried to address each comment to the best of our abilities. We believe that the comments helped us greatly to improve the manuscript.

Attachments
Attachment
Submitted filename: Response to Reviewers 21.12.2020.docx
Formally Accepted
Acceptance Letter - Wen-Jun Tu, Editor

PONE-D-20-29228R2

Impact of COVID-19 on hospital admission of acute stroke patients in Bangladesh

Dear Dr. Hasan:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Wen-Jun Tu

Academic Editor

PLOS ONE

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