Reviewer’s report
Title: 
Are Gastrointestinal Symptoms Associated with Higher Risk of Mortality
in COVID-19 Patients? A Systematic Review and Meta-Analysis
Version: 
1 
Date: 
23 Mar 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
I have reviewed this manuscript. I am unsure whether there were any previous
reviewers comments, but comments were addressed to the Editor. The study has
a clear objective and a protocol has been published. There are a few comments
for the authors, mainly about some of the conclusions made that could be more
objective.
REQUESTED REVISIONS: 
In Line 158: What proportion of the study population included does the four
studies from the USA/Europe represent? Please include that as it is important for
this to clarify the point made.
Line 195: Why are these results considered odd? 
Page 7, Lines 198-Page 8 line 204 "Thus the heterogeneity in the included
studies might be partially related to the patient selection bias in USA and Europe
hospitals. On the other hand, follow-up time in the 4 studies was relatively short
because of the urgent need for..." The conclusions drawn here seem biased and
subjective. The info preceding this indicates that persons with GI symptoms
were prioritised for treatment in hospital which is a desirable and consistent
practice across the four studies. How can this be described as biased? The fact
that the outcomes do not match what the authors are looking for, does that make
it biased? Authors need to look for a more objective perspective on the
difference in the results obtained for studies in USA/Europe vs China. A
reasonable conclusion can be focused on any difference in clinical practice or
protocols between different settings and the timeliness of interventions that have
lead to different outcomes in each setting. 
Pg 8, line 225: It is unclear what this sentence means 'The pooled OR estimate
tended to favor the presence of GI symptoms...'. Please rephrase.
Pg 11, Line 295: Once again, I suggest the authors be more objective with their
conclusion. The USA studies were generally larger sample size and the OR for
that subgroup indicated GI symptoms were more protective. The Chinese studies
OR was 1.01 and was not significant. So the general result of this study is that GI
symptoms are not associated with worse prognosis. Based on statistical
principles, the larger sample size in the sub-group of USA/Europe studies
indicated a stronger support for the outcome, which confirms the overall result.
ADDITIONAL REQUESTS/SUGGESTIONS: 
A few grammatical errors.
Publons Reviewer Recognition
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review directly to Publons (a subsidiary of Clarivate Analytics). If you would
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sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
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No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Are Gastrointestinal Symptoms Associated with Higher Risk of Mortality
in COVID-19 Patients? A Systematic Review and Meta-Analysis
Version: 
1 
Date: 
23 Mar 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
I have reviewed this manuscript. I am unsure whether there were any previous
reviewers comments, but comments were addressed to the Editor. The study has
a clear objective and a protocol has been published. There are a few comments
for the authors, mainly about some of the conclusions made that could be more
objective.
REQUESTED REVISIONS: 
In Line 158: What proportion of the study population included does the four
studies from the USA/Europe represent? Please include that as it is important for
this to clarify the point made.
Line 195: Why are these results considered odd? 
Page 7, Lines 198-Page 8 line 204 "Thus the heterogeneity in the included
studies might be partially related to the patient selection bias in USA and Europe
hospitals. On the other hand, follow-up time in the 4 studies was relatively short
because of the urgent need for..." The conclusions drawn here seem biased and
subjective. The info preceding this indicates that persons with GI symptoms
were prioritised for treatment in hospital which is a desirable and consistent
practice across the four studies. How can this be described as biased? The fact
that the outcomes do not match what the authors are looking for, does that make
it biased? Authors need to look for a more objective perspective on the
difference in the results obtained for studies in USA/Europe vs China. A
reasonable conclusion can be focused on any difference in clinical practice or
protocols between different settings and the timeliness of interventions that have
lead to different outcomes in each setting. 
Pg 8, line 225: It is unclear what this sentence means 'The pooled OR estimate
tended to favor the presence of GI symptoms...'. Please rephrase.
Pg 11, Line 295: Once again, I suggest the authors be more objective with their
conclusion. The USA studies were generally larger sample size and the OR for
that subgroup indicated GI symptoms were more protective. The Chinese studies
OR was 1.01 and was not significant. So the general result of this study is that GI
symptoms are not associated with worse prognosis. Based on statistical
principles, the larger sample size in the sub-group of USA/Europe studies
indicated a stronger support for the outcome, which confirms the overall result.
ADDITIONAL REQUESTS/SUGGESTIONS: 
A few grammatical errors.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Are Gastrointestinal Symptoms Associated with Higher Risk of Mortality
in COVID-19 Patients? A Systematic Review and Meta-Analysis
Version: 
1 
Date: 
23 Mar 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
I have reviewed this manuscript. I am unsure whether there were any previous
reviewers comments, but comments were addressed to the Editor. The study has
a clear objective and a protocol has been published. There are a few comments
for the authors, mainly about some of the conclusions made that could be more
objective.
REQUESTED REVISIONS: 
In Line 158: What proportion of the study population included does the four
studies from the USA/Europe represent? Please include that as it is important for
this to clarify the point made.
Line 195: Why are these results considered odd? 
Page 7, Lines 198-Page 8 line 204 "Thus the heterogeneity in the included
studies might be partially related to the patient selection bias in USA and Europe
hospitals. On the other hand, follow-up time in the 4 studies was relatively short
because of the urgent need for..." The conclusions drawn here seem biased and
subjective. The info preceding this indicates that persons with GI symptoms
were prioritised for treatment in hospital which is a desirable and consistent
practice across the four studies. How can this be described as biased? The fact
that the outcomes do not match what the authors are looking for, does that make
it biased? Authors need to look for a more objective perspective on the
difference in the results obtained for studies in USA/Europe vs China. A
reasonable conclusion can be focused on any difference in clinical practice or
protocols between different settings and the timeliness of interventions that have
lead to different outcomes in each setting. 
Pg 8, line 225: It is unclear what this sentence means 'The pooled OR estimate
tended to favor the presence of GI symptoms...'. Please rephrase.
Pg 11, Line 295: Once again, I suggest the authors be more objective with their
conclusion. The USA studies were generally larger sample size and the OR for
that subgroup indicated GI symptoms were more protective. The Chinese studies
OR was 1.01 and was not significant. So the general result of this study is that GI
symptoms are not associated with worse prognosis. Based on statistical
principles, the larger sample size in the sub-group of USA/Europe studies
indicated a stronger support for the outcome, which confirms the overall result.
ADDITIONAL REQUESTS/SUGGESTIONS: 
A few grammatical errors.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant