Review for 10.1186/s12876-022-02132-0 (2022)

Reviewer’s report
Title: 
Are Gastrointestinal Symptoms Associated with Higher Risk of Mortality
in COVID-19 Patients? A Systematic Review and Meta-Analysis
Version: 
2 
Date: 
02 Sep 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses one
or several testable research questions? (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 sufficient
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 - Has the author addressed your
concerns sufficiently for you to now recommend the work as a technically sound
contribution? If not, can further revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: The authors have provided satisfactory feedback to
the responses. I also commend the authors for updating their Literature searches
and adding more recently published data. There are a few additional comments
that have been raised based on the edits made that are outlined below. The main
comment relates to the age-related analysis that has show significant differences
based on location. This is a very important finding and should not be glossed
over by the authors. Specific comments are follow.
REQUESTED REVISIONS: 
Line 137: Can we add a reference for the Newcastle-Ottawa Scale.
Line 186 - change 'had' to 'have'.
Line 189: Please add back the p value for the I squared statistic).
Lines 212-217: I beleive the analysis on age related difference is a very
important clinical finding and can be added in the manuscript here. It would be
important to highight that there is an increased risk among older patients
presenting with GI symptoms compared with younger persons. The authors have
provided a sensible response in the feedback section. this could be added in the
manuscript here.
Lines 212-217: I believe the analysis on age related difference is a very
important clinical finding and can be added in the manuscript here. It would be
important to highlight that there is an increased risk among older patients
presenting with GI symptoms compared with younger persons. The authors have
provided a sensible response in the feedback section. this could be added in the
manuscript here.
Line 217: This is a very important finding. I am not sure I understand the
meaning of the term 'attenuated' here. I suggest replace with another word to
improve clarity of this sentence.
Lines 286-298: Please also refer to note at Line 213. The information here
describing the sub-analysis are very important findings and should be moved to
the findings section. I would suggest adding the tables or figures corresponding
to this finding if these are available. Then the discussion can continue about the
significance of this finding on the respective respective regions and generally. 
Line 297-298: Once again, it is important to underscore that since age is a
significant predictor of COVID-19 outcomes, the differences in mortality for
patients of a certain age is an important finding in this study, that should not be
brushed over. This is a particular value of this meta-analysis. I recommend the
authors add a few more discussion points on this in the context of the reviewed
literature that may be useful for clinicians and public health experts planning for
health care resources to manage older COVID-19 cases exhibiting GI symptoms.
Line 362-364: I do not agree with the authors that the difference in age among
patients in some locations is a limitation. I think this is one of the novel findings
of this meta-analysis and this should be carefully described and discussed in the
paper. The subgroup analysis by age groups should be more carefully reported. 
Table 3: The critical analysis missing from Table 3 is the age related analysis by
sub-region.
ADDITIONAL REQUESTS/SUGGESTIONS: 
I suggest adding the age related sub-analysis by region as this is a critical
finding. In my opinion this IS the major finding of this study and it needs to be
given the prominence it deserves - maybe this can be added to Table 3.
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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?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes