PONE-D-21-18070

Association of ABO blood group with COVID-19 severity, acute phase reactants and mortality

PLOS ONE

Dear Dr. Malik,

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 address the issues and revise accordingly if able.

Please submit your revised manuscript by Aug 02 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'.
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• 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. 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,

Robert Jeenchen Chen, MD, MPH

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: No

Reviewer #2: No

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

Reviewer #1: No

Reviewer #2: 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

**********

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: No

Reviewer #2: No

**********

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 study entitled “Association of ABO blood group with COVID-19 severity, acute phase reactants and Mortality” retrospectively analyzed the association between blood ABO groups and disease severity/mortality among the COVID-19 patients.

Some comments and questions were raised for the authors.

1. Many confounding factors would affect the clinical outcome (severity and mortality), such as comorbidities and medical treatment. Therefore, to minimize confounding bias, a multivariate analysis which includes variables of blood groups, comorbidities, and treatment should be performed to determine the risk factors associated with disease severity or mortality. If a certain blood group remains a risk factor for severe disease or mortality after a multivariate analysis, it would be more convincing to state that certain blood group is associated with severe disease and higher mortality.

2. The presentation and interpretation of some statistical results were not precise or not consistent throughout the manuscript. For example,

(1) Abstract, conclusions, “…hospital stay, severity of disease, and mortality were associated with blood group A.” -> However, hospital stay was not different between all four blood groups as mentioned in the Result section “Patients with AB blood group stayed a median (IQR) of 14 (5, 27) days while A blood group cohort stayed 13 (6,27) days. It was statistically non-significant between all four groups.” In addition, the mortality rates among 4 blood groups were not statistically different according to Table 1.

(2) Results: “Regarding severity of COVID-19 disease, there was a trend towards critical disease in blood groups A and O (n=83, 41.1%; n=183, 35.1%; OR, 11.34 (95% CI, 46.79-53.22); p<0.001).” Why was OR ratio here beyond the range of 95% CI? In addition, to determine the effect of blood group A and O on disease severity, blood group A and O should have individual OR.

(3) Discussion, “By contrast, we observed mild disease to be prevalent in the B and AB blood groups.“ -> The statement is not consistent with the data in Table 1.

(4) Discussion, “Acute phase reactants were majorly deranged in blood group O as compared to other groups and hospital stay was associated more with A and AB blood groups”. -> However, according to Figure 2, blood group O appeared to have the highest levels of acute phase proteins, whereas blood group O had the lowest levels of acute phase proteins in Table 1. Please check these data again.

(5) Conclusions, “In conclusion, we demonstrate that male patients with blood group A and O are associated with an increased risk of severe COVID-19 disease after gender stratification while group A is associated with increased hospital stay and mortality.”-> According to the context, the effect of gender was not examined in this study. Furthermore, the association of group A with increased hospital stay and mortality was not evident according to Table 1.

(6) What did “the number of days” mean in the figure 1 (cumulative incidence vs numbers of days)? What’s the unit for incidence here?

Overall, it would be helpful if the statistical analysis of this study is carefully reviewed again by a statistics expert.

Minor comments:

1. Method, “The severity of COVID-19 was classified into, mild, moderate, and critical according to the Centers for Disease Control (CDC) guidelines.” -> Please provide reference here.

2. Please define the headings of Table 3 (B, SE, Wald).

Reviewer #2: Several comments,

I. In general, the English grammar should be checked before submission

II. In the introduction, the authors should clearly describe the current status of studies about the association between ABO blood types and COVID-19. Both pros and cons options about this issue, especially severity and mortality, should also be cited in this section. Moreover, this section also lacks flow and transition sentences between paragraphs.

III. Materials and Methods

A. The definitions of COVID-19 severity are incorrect.

B. How to define COVID-19 related mortality?

IV. Results

A. How about the distribution of comorbidities (other than those described by authors) between different blood types?

B. The therapeutic strategies between patients with different blood types should be pointed out.

V. Discussion

A. The second paragraph only describes the results of this study. No comparison was made with prior studies.

B. In the third paragraph, the authors described different prevalent results of blood types among various studies, including themselves. More discussion should be made about such issues.

VI. Tables and figures

A. Table 2 is not clear

B. The resolution of figures is poor

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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

[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.

PONE-D-21-18070R1

Association of ABO blood group with COVID-19 severity, acute phase reactants and mortality

PLOS ONE

Dear Dr. Malik,

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 address the issues and revise accordingly.

Please submit your revised manuscript by Sep 11 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. 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,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

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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: (No Response)

Reviewer #3: 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: No

Reviewer #3: No

**********

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

Reviewer #1: No

Reviewer #3: 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 #3: 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: No

Reviewer #3: 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: In general, the presentation and interpretation of statistical results was still not precise in this revised manuscript.

Some comments and questions are listed below:

- Abstract: “Acute phase protein reactants” was included in the manuscript title; however, nothing was mentioned in the abstract.

- Abstract (Method): Information provided in the method was very limited.

- Abstract (Results): “Patients with AB blood group stayed a median (IQR) of 14 (5, 27) days while A blood group cohort stayed 13 (6,27) days and overall…” It is difficult to understand why the authors mentioned days of hospital stay for AB blood group and A blood group here, as the days of hospital stay were not significantly different between 4 groups. Why was AB blood group mentioned here in particular?

- Abstract (Results): “…overall 10.6% COVID-19-related mortality was observed at our center, with 13.9% in blood group A as the majority of COVID-19 deaths.” This part could be written as a separate sentence. In addition, although patients of blood group A had a higher proportion of mortality, patients with blood group O contributed to the majority of deaths.

- Abstract & Results: “Regarding severity of COVID-19 disease, there was a trend towards critical disease in blood group A (n=83, 41.1%; OR 0.257 (95% CI:0.167-1.136); p<0.001) and O (n=183, 35.1%; OR 0.438 (95% CI: 0.168-1.139); p<0.001).” The OR (95% CI) presented in this sentence were OR (95% CI) for “mortality” shown in Table 2 (multivariate analysis), but the proportions and p values presented in this sentence were the proportions and p values for critical diseases shown in Table 1 (univariate analysis). The presentation and interpretation of statistical results is confusing.

Result

- Please briefly describe the results of acute phase protein reactants in the text.

- “Multivariate analysis (after adjusting age, gender, and comorbidities) did not show any blood group in this cohort (Table 2).” This sentence was not clear.

- As the study aimed to exam the association between the blood group and disease severity, multivariate analysis should also be performed to identify risk factors associated with severity (as done in Table 2 which examined the association between the blood group and mortality by multivariate analysis.)

Discussion

- “, blood group O was linked to severe derangement of acute-phase reactants.” Data from Table 1 and Figure 2did not support this statement.

Conclusion

- “Alteration of the acute phase reactants is positively associated with blood type A.” Data from Table 1 and Figure 2 did not support this statement, and this statement was not consistent with “blood group O was linked to severe derangement of acute-phase reactants” mentioned in the Discussion section.

Figure

The resolution of Figure 2 was not enough.

Reviewer #3: Reviewer 2 asked

A. How about the distribution of comorbidities (other than those described by authors)

between different blood types?

B. The therapeutic strategies between patients with different blood types should be

pointed out.

Response: dear sit I regret to inform that no other comorbidities were collected in our

study and no therapeutic strategy was noted. That data is not available to us

unfortunately.

These are major confounding factors and should be assessed.

Other confounding factor is the time from the onset of the disease to hospital admission. It should be included to the analysis.

Please provide rationale support to assuring adequate sample power.

The authors stated that p"articipants had blood group O as the prevalent blood type." However this percentage should be compared with the distribution of blood groups in the country.

**********

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 #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.

PONE-D-21-18070R2Association of ABO blood group with COVID-19 severity, acute phase reactants and mortalityPLOS ONE

Dear Dr. Malik,

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 address the concerns of the reviewer with unfavorable opinions and revise the manuscript.  If not amendable, maybe put into the Limitations.

Please submit your revised manuscript by Oct 21 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: 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,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

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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: (No Response)

Reviewer #4: All comments have been addressed

Reviewer #5: 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: No

Reviewer #4: Yes

Reviewer #5: Yes

**********

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

Reviewer #1: I Don't Know

Reviewer #4: Yes

Reviewer #5: 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 #4: Yes

Reviewer #5: 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: No

Reviewer #4: Yes

Reviewer #5: 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 the earlier comments have been addressed by the authors. However, the interpretation and presentation of some results still appeared inaccurate. In many instances, some minor differences existed between groups without statistical differences, but they were presented as meaningful findings. Some expressions are also confusing, for example, “the frequency of acute phase reactants with ABO blood type” in text and “Frequency distribution of acute phase reactants in correlation with ABO blood group” in Figure 2. In addition, the data of acute phase reactants in table 1 looked quite different with those in Figure 2.

Reviewer #4: (No Response)

Reviewer #5: (No Response)

**********

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 #4: Yes: Parisa Sabbagh

Reviewer #5: Yes: Hamed Kalani

[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.

PONE-D-21-18070R3Association of ABO blood group with COVID-19 severity, acute phase reactants and mortalityPLOS ONE

Dear Dr. Malik,

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 revise.

Please submit your revised manuscript by Jan 06 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,

Robert Jeenchen Chen, MD, MPH

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.

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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 #4: (No Response)

Reviewer #5: 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 #4: Yes

Reviewer #5: Yes

**********

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

Reviewer #4: Yes

Reviewer #5: 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 #4: Yes

Reviewer #5: 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 #4: Yes

Reviewer #5: 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 #4: Its a good and useful article. And also it has understandable and fluent text. Subject is updated and its one of the most important problem nowadays.

Reviewer #5: 1- Move sentence “Alteration of the acute phase reactants was not positively associated with any specific blood type” from section of Conclusion in Abstract to section of Results.

2- It should be noted in the discussion that the outcome of patients' treatment was not examined in this study and this is one of the limitations of this study.

3- Check for spelling and typographical errors throughout the text.

**********

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 #4: Yes: Parisa Sabbagh

Reviewer #5: No

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Association of ABO blood group with COVID-19 severity, acute phase reactants and mortality

PONE-D-21-18070R4

Dear Dr. Malik,

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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PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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Reviewer #4: All comments have been addressed

Reviewer #5: All comments have been addressed

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: Yes

Reviewer #5: Yes

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Reviewer #4: (No Response)

Reviewer #5: (No Response)

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Reviewer #4: Yes: Parisa Sabbagh

Reviewer #5: No