Multiple Sclerosis Treatment in the COVID-19 Era: A Risk-Benefit Approach

Round 1

Reviewer 1 Report

Dear Sirs, this review is an overview of previous published materials regarding Covid vaccination and DMT treatment in MS patients. However I consider a more profound analysis including the present experience that is stated in major MS guidelines for Covid vaccination issued by the most important medical authorities like FDA, EAN would increase the value of your work.

Author Response

Dear Editor

Dear Reviewers,

 

we sincerely thank the reviewer for their effort to produce an excellent revision, which substantially improved the quality of the paper.

We enclosed a clear file and marked-up file with corrections: the new text is marked in red and the old one in strikethrough.

 

Please find below the point-by-point answer to reviewers comments:

                                                                                               

• Reviewer #1:
  • Comment # 1: “Dear Sirs, this review is an overview of previous published materials regarding Covid vaccination and DMT treatment in MS patients. However I consider a more profound analysis including the present experience that is stated in major MS guidelines for Covid vaccination issued by the most important medical authorities like FDA, EAN would increase the value of your work.”

Answer: a paragraph summarizing guidelines by regulatory agencies, scientific societies and Italian Ministry of Health has been added in the results section

• Reviewer #2:
  • Comment #1: “A graphical abstract summarizing the manuscript is highly recommended.”

Answer: a graphical abstract has been added

 

• Comment #2 : “Abstract: According to the Journal’s guidelines, the abstract should be introduced as a single paragraph, following the style of structured abstracts, but without headings. Please correct the actual one. Please expand it to 200 words, proportionally including background, rationale, purpose, and conclusion. Also please re-examine the validity of using abbreviations such as pwMS and DMDs for this manuscript.”

Answer: abstract has been revised according to the Journal’s guidelines

 

• Comment #3: “Keywords: Please consider adding ‘MS therapy-related risks’ as a keyword and list up to ten keywords.”

Answer: Keywords has been up-dated as indicated

 

• Comment #4: “In general, I recommend authors to use more evidence to back their claims, especially in the Introduction of the review, which I believe is currently lacking. Thus, I recommend the authors to attempt to deepen the subject of their manuscript, as the bibliography is too concise: nonetheless, in my opinion, less than 50 articles for a literature review are really insufficient. Indeed, currently authors cite only 25 papers, and they are too low. Therefore, I suggest the authors to focus their efforts on researching more relevant literature: I believe that adding more studies and reviews will help them to provide better and more accurate background to this study. In this review, I will try to help the authors by suggesting some relevant literature of my knowledge that suit their manuscript.”

Answer: the introduction has been corrected following the reviewers indications and the bibliography has been expanded as well.

 

• Comment #5: “Introduction, line 26: please specify the full name ‘people with Multiple Sclerosis’ before the acronym ‘pwMS’.”

Answer: the change has been made.

 

• Comment #6: “Introduction: As suggested before, I strongly recommend authors to use more evidence to back their claims, especially in the Introduction of the review briefly summarizing risk factors, pathogenesis, diagnosis, progression, comorbidity, prognosis, biomarkers, current treatment, and a challenge (https://doi.org/10.3390/biomedicines9050517; https://doi.org/10.3390/ijms21249338; https://doi.org/10.3390/biomedicines8100406; https://doi.org/10.3390/diagnostics12010130; https://doi.org/10.3390/ijerph18115588; doi: 10.3389/fneur.2021.716195; https://doi.org/10.3390/jpm11101032). Actually, the authors take a rather narrow view on the current state of knowledge surrounding COVID-19 and the associated psycho-social and economic effects, focusing on the impact that risk factors for SARS-CoV-2 infection have on Multiple Sclerosis (MS). Nevertheless, I think that a deeper examination on the current state of knowledge regarding the spreading of COVID-19 and the associated impact on psycho-social well-being would provide a better characterization and useful background in this context. Accordingly, I would suggest some references that would be crucial in this section, such as a recent review in in which authors described COVID-19 pathogenesis (https://doi.org/10.1177/1073858420941476), and also a crucial investigation on resilience factors during the pandemic (https://doi.org/10.1038/s41398-020-01150-4), in which authors showed that mental resilience in 15.970 European participants, as an outcome of the perceived experiences and conceptualized as good mental health despite COVID-19 stressor, is mediated by the ability to easily recover from stress. Thereby, it is demonstrated that good stress response and positive appraisal, specifically of the consequences of the Corona crisis, are the strongest factors as compared to other psychological factors.”

Answer: Introduction has been corrected and a paragraph summarizing MS risk factors, pathogenesis, diagnosis and treatment has been added, the papers suggested by the reviewer has been included. A paragraph that better describes COVID-19 psycho-social effects has been added.

 

• Comment #7: “Materials and Methods:I suggest Authors to reorganize/rewrite this paragraph because, as it stands, it appears to be too much dispersive and describes the research procedures in an excessively broad way. I would ask the authors to clarify the criteria they decided to use for studies collection in their review: they should specify the number of studies included in the review and the requirements used to decide whether a study met the inclusion/exclusion criteria for the synthesis; they also should provide a more detailed description of all other variables for which data were sought (diagnostic criteria for COVID-19 infection and MS, information about vaccine, effects of COVID-19 vaccination on MS) and briefly present results of all statistical syntheses conducted.”

Answer: Materials and Methods section has been corrected according to the reviewers comment. This is a narrative review, and a systematic review of the literature including a meta-analysis of the variable is beyond the scope of the paper, so we regret to inform the reviewer that we didn’t perform a statistical analysis, but we added a paragraph in the discussion highlighting this limitation of the study.

 

• Comment #8: “Results: Please reorganize this section for clarity, providing full statistical information to ensure in-depth understanding and replicability of the findings. Also, please present statistical data in more detailed tables.

Answer: This is a narrative review, and a meta-analysis of the variable is beyond the scope of the paper, so we regret to inform the reviewer that we didn’t present a statistical analysis of the variables. This limitation has been discussed adding a paragraph in the discussion.

 

• Comment #9: ” Discussion: In my opinion, this review would be more compelling and useful to a broad readership if the authors moved beyond and discussed theoretical and methodological avenues in need of refinement, using this evidence to suggest a path forward. Technically, this manuscript focuses on different aspects of SARS-CoV-2 infection in pwMS, specifically on risks related to SARS-CoV-2 infection in MS. Still, I believe that it may be useful adding some evidence that showed the impact of COVID-19 on social behavior as well, focusing on the association between changes in social-distance levels and neural activation: a recent study showed how multisensory neurons in frontal and parietal areas, involved in representation of tactile information on the body and visual or auditory stimuli occurring in the personal space, support the capacity to read signals in the environment and action prediction, thus evoking modulation of autonomic arousal as a response to external stimuli (i.e., emotional stimuli) that appear in the peri-personal space, resulting in modulation of social distance (https://doi.org/10.1007/s00221-020-05829-4). In according with the previous point, to better characterize how COVID-19 perceived threat can affect behavioral expressions associated with distance from others, thus determining voluntary reduction of social interaction, I would recommend another interesting study. Here, authors analyzed how social distance can be modulated by arousing stimuli (i.e., emotional cues which can be interpreted as potentially threatening situations), and how this interpretation triggers a number of physiological responses that help regulating the distance between ourselves and others during social interaction (https://doi.org/10.1038/s41598-021-82223-2). Results from this research highlighted how context flexibly modulates interpersonal distance and how the current pandemic situation influences interpersonal distance evaluations overall.”

Answer: The discussion has been corrected and we added a paragraph discussing the effect of COVID-19 on neural networks of fear and peri-personal space and its relation-ship with social distancing. This is a very interesting point.

 

• Comment #10: “ I think the ‘Conclusions’ paragraph would benefit from some thoughtful as well as in-depth considerations by the authors, because as it stands, it lists down all the main findings of the research, without really stressing the theoretical significance of the study. Authors should make an effort, trying to explain the theoretical implication as well as the translational application of their research.”

Answer: Conclusion has been changed in order to describe the pragmatic implication of the literature review.

 

• Comment #11: “ In according to the previous comment, I would ask the authors to include a ‘Limitations and future directions’ section before the end of the manuscript, in which authors can describe in detail and report all the technical issues brought to the surface.”

Answer: the limitation of the study has been addressed in the discussion section.

 

• Comment #12: “Regarding theTables: please provide an explanatory caption for each table within the text.”

Answer: an explanatory caption has been added for each of the tables

 

• Comment #13: “References:Authors should consider revising the bibliography, as there are several incorrect citations. Indeed, according to the Journal’s guidelines, they should provide the abbreviated journal name in italics, the year of publication in bold, the volume number in italics for all the references.

Answer: References has been revised according to the indications

 

 

Author Response File: Author Response.docx

Reviewer 2 Report

9 March 2022

Manuscript ID: neurolint-1621643

Type: Review

Title: “Multiple Sclerosis treatment in the COVID-19 era: a rik-benefit approach” by Immovilli P et al., submitted to Neurology International

Dear Authors,

Immovilli and colleagues in the present review entitled ‘Multiple Sclerosis treatment in the COVID-19 era: a risk-benefit approach’, investigated the current status of knowledge of SARS-CoV-2 vaccine and possible evidence for future strategies in the clinical management of people with Multiple Sclerosis (MS). For this purpose, authors selected some evidence that explored risk factors for severe COVID-19 and vaccination response in people with MS, and reported a synthesis of possible future strategies to reduce risks related to SARS-CoV-2 infection in people with MS. The results of this review shed light on the possible application of multilevel strategy that could be applied as a risk management plan, with multilevel interventions aimed at obtaining a better understanding of the risks for severe COVID-19 in pwMS, identification of the most appropriate vaccination schedule safe for people on disease modifying drugs (DMDs) and strict follow-up of high risk pwMS to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risk in pwMS.

The main strength of this manuscript is that it addresses an interesting and timely question, providing a captivating interpretation and describing risks of vulnerable people with MS being exposed to SARS-CoV-2. In general, I think the idea of this review is really interesting and the authors’ fascinating observations on this timely topic may be of interest to the readers of Neurology International. However, some comments, as well as some crucial evidence that should be included to support the author’s argumentation, needed to be addressed to improve the quality of the manuscript, its adequacy, and its readability prior to the publication in the present form, in particular reshaping parts of the Introduction and Discussion sections by adding more evidence and theoretical constructs.

Please consider the following comments:

1. A graphical abstract summarizing the manuscript is highly recommended.
2. Abstract: According to the Journal’s guidelines, the abstract should be introduced as a single paragraph, following the style of structured abstracts, but without headings. Please correct the actual one. Please expand it to 200 words, proportionally including background, rationale, purpose, and conclusion. Also please re-examine the validity of using abbreviations such as pwMS and DMDs for this manuscript.
3. Keywords: Please consider adding ‘MS therapy-related risks’ as a keyword and list up to ten keywords.
4. In general, I recommend authors to use more evidence to back their claims, especially in the Introduction of the review, which I believe is currently lacking. Thus, I recommend the authors to attempt to deepen the subject of their manuscript, as the bibliography is too concise: nonetheless, in my opinion, less than 50 articles for a literature review are really insufficient. Indeed, currently authors cite only 25 papers, and they are too low. Therefore, I suggest the authors to focus their efforts on researching more relevant literature: I believe that adding more studies and reviews will help them to provide better and more accurate background to this study. In this review, I will try to help the authors by suggesting some relevant literature of my knowledge that suit their manuscript.
5. Introduction, line 26: please specify the full name ‘people with Multiple Sclerosis’ before the acronym ‘pwMS’.
6. Introduction: As suggested before, I strongly recommend authors to use more evidence to back their claims, especially in the Introduction of the review briefly summarizing risk factors, pathogenesis, diagnosis, progression, comorbidity, prognosis, biomarkers, current treatment, and a challenge (https://doi.org/10.3390/biomedicines9050517; https://doi.org/10.3390/ijms21249338; https://doi.org/10.3390/biomedicines8100406; https://doi.org/10.3390/diagnostics12010130; https://doi.org/10.3390/ijerph18115588; doi: 10.3389/fneur.2021.716195; https://doi.org/10.3390/jpm11101032). Actually, the authors take a rather narrow view on the current state of knowledge surrounding COVID-19 and the associated psycho-social and economic effects, focusing on the impact that risk factors for SARS-CoV-2 infection have on Multiple Sclerosis (MS). Nevertheless, I think that a deeper examination on the current state of knowledge regarding the spreading of COVID-19 and the associated impact on psycho-social well-being would provide a better characterization and useful background in this context. Accordingly, I would suggest some references that would be crucial in this section, such as a recent review in in which authors described COVID-19 pathogenesis (https://doi.org/10.1177/1073858420941476), and also a crucial investigation on resilience factors during the pandemic (https://doi.org/10.1038/s41398-020-01150-4), in which authors showed that mental resilience in 15.970 European participants, as an outcome of the perceived experiences and conceptualized as good mental health despite COVID-19 stressor, is mediated by the ability to easily recover from stress. Thereby, it is demonstrated that good stress response and positive appraisal, specifically of the consequences of the Corona crisis, are the strongest factors as compared to other psychological factors.
7. Materials and Methods: I suggest Authors to reorganize/rewrite this paragraph because, as it stands, it appears to be too much dispersive and describes the research procedures in an excessively broad way. I would ask the authors to clarify the criteria they decided to use for studies collection in their review: they should specify the number of studies included in the review and the requirements used to decide whether a study met the inclusion/exclusion criteria for the synthesis; they also should provide a more detailed description of all other variables for which data were sought (diagnostic criteria for COVID-19 infection and MS, information about vaccine, effects of COVID-19 vaccination on MS) and briefly present results of all statistical syntheses conducted.
8. Results: Please reorganize this section for clarity, providing full statistical information to ensure in-depth understanding and replicability of the findings. Also, please present statistical data in more detailed tables.
9. Discussion: In my opinion, this review would be more compelling and useful to a broad readership if the authors moved beyond and discussed theoretical and methodological avenues in need of refinement, using this evidence to suggest a path forward. Technically, this manuscript focuses on different aspects of SARS-CoV-2 infection in pwMS, specifically on risks related to SARS-CoV-2 infection in MS. Still, I believe that it may be useful adding some evidence that showed the impact of COVID-19 on social behavior as well, focusing on the association between changes in social-distance levels and neural activation: a recent study showed how multisensory neurons in frontal and parietal areas, involved in representation of tactile information on the body and visual or auditory stimuli occurring in the personal space, support the capacity to read signals in the environment and action prediction, thus evoking modulation of autonomic arousal as a response to external stimuli (i.e., emotional stimuli) that appear in the peri-personal space, resulting in modulation of social distance (https://doi.org/10.1007/s00221-020-05829-4). In according with the previous point, to better characterize how COVID-19 perceived threat can affect behavioral expressions associated with distance from others, thus determining voluntary reduction of social interaction, I would recommend another interesting study. Here, authors analyzed how social distance can be modulated by arousing stimuli (i.e., emotional cues which can be interpreted as potentially threatening situations), and how this interpretation triggers a number of physiological responses that help regulating the distance between ourselves and others during social interaction (https://doi.org/10.1038/s41598-021-82223-2). Results from this research highlighted how context flexibly modulates interpersonal distance and how the current pandemic situation influences interpersonal distance evaluations overall.
10. I think the ‘Conclusions’ paragraph would benefit from some thoughtful as well as in-depth considerations by the authors, because as it stands, it lists down all the main findings of the research, without really stressing the theoretical significance of the study. Authors should make an effort, trying to explain the theoretical implication as well as the translational application of their research.
11. In according to the previous comment, I would ask the authors to include a ‘Limitations and future directions’ section before the end of the manuscript, in which authors can describe in detail and report all the technical issues brought to the surface.
12. Regarding the Tables: please provide an explanatory caption for each table within the text.
13. References: Authors should consider revising the bibliography, as there are several incorrect citations. Indeed, according to the Journal’s guidelines, they should provide the abbreviated journal name in italics, the year of publication in bold, the volume number in italics for all the references.

Overall, the manuscript contains 2 tables and 25 references. In my opinion, the number of references it is dramatically low for an original research article, and this prevents the possibility of publishing it in this form – in my opinion. References should be more than 150 for original literature reviews. However, the manuscript might carry important value presenting risks of vulnerable people with MS being exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

I hope that, after these careful revisions, the manuscript can meet the Journal’s high standards for publication. I am available for a new round of revision of this article.

I declare no conflict of interest regarding this manuscript.

Best regards,

 

Reviewer

Author Response

Dear Editor

Dear Reviewers,

 

we sincerely thank the reviewer for their effort to produce an excellent revision, which substantially improved the quality of the paper.

We enclosed a clear file and marked-up file with corrections: the new text is marked in red and the old one in strikethrough.

 

Please find below the point-by-point answer to reviewers comments:

                                                                                               

• Reviewer #1:
  • Comment # 1: “Dear Sirs, this review is an overview of previous published materials regarding Covid vaccination and DMT treatment in MS patients. However I consider a more profound analysis including the present experience that is stated in major MS guidelines for Covid vaccination issued by the most important medical authorities like FDA, EAN would increase the value of your work.”

Answer: a paragraph summarizing guidelines by regulatory agencies, scientific societies and Italian Ministry of Health has been added in the results section

• Reviewer #2:
  • Comment #1: “A graphical abstract summarizing the manuscript is highly recommended.”

Answer: a graphical abstract has been added

 

• Comment #2 : “Abstract: According to the Journal’s guidelines, the abstract should be introduced as a single paragraph, following the style of structured abstracts, but without headings. Please correct the actual one. Please expand it to 200 words, proportionally including background, rationale, purpose, and conclusion. Also please re-examine the validity of using abbreviations such as pwMS and DMDs for this manuscript.”

Answer: abstract has been revised according to the Journal’s guidelines

 

• Comment #3: “Keywords: Please consider adding ‘MS therapy-related risks’ as a keyword and list up to ten keywords.”

Answer: Keywords has been up-dated as indicated

 

• Comment #4: “In general, I recommend authors to use more evidence to back their claims, especially in the Introduction of the review, which I believe is currently lacking. Thus, I recommend the authors to attempt to deepen the subject of their manuscript, as the bibliography is too concise: nonetheless, in my opinion, less than 50 articles for a literature review are really insufficient. Indeed, currently authors cite only 25 papers, and they are too low. Therefore, I suggest the authors to focus their efforts on researching more relevant literature: I believe that adding more studies and reviews will help them to provide better and more accurate background to this study. In this review, I will try to help the authors by suggesting some relevant literature of my knowledge that suit their manuscript.”

Answer: the introduction has been corrected following the reviewers indications and the bibliography has been expanded as well.

 

• Comment #5: “Introduction, line 26: please specify the full name ‘people with Multiple Sclerosis’ before the acronym ‘pwMS’.”

Answer: the change has been made.

 

• Comment #6: “Introduction: As suggested before, I strongly recommend authors to use more evidence to back their claims, especially in the Introduction of the review briefly summarizing risk factors, pathogenesis, diagnosis, progression, comorbidity, prognosis, biomarkers, current treatment, and a challenge (https://doi.org/10.3390/biomedicines9050517; https://doi.org/10.3390/ijms21249338; https://doi.org/10.3390/biomedicines8100406; https://doi.org/10.3390/diagnostics12010130; https://doi.org/10.3390/ijerph18115588; doi: 10.3389/fneur.2021.716195; https://doi.org/10.3390/jpm11101032). Actually, the authors take a rather narrow view on the current state of knowledge surrounding COVID-19 and the associated psycho-social and economic effects, focusing on the impact that risk factors for SARS-CoV-2 infection have on Multiple Sclerosis (MS). Nevertheless, I think that a deeper examination on the current state of knowledge regarding the spreading of COVID-19 and the associated impact on psycho-social well-being would provide a better characterization and useful background in this context. Accordingly, I would suggest some references that would be crucial in this section, such as a recent review in in which authors described COVID-19 pathogenesis (https://doi.org/10.1177/1073858420941476), and also a crucial investigation on resilience factors during the pandemic (https://doi.org/10.1038/s41398-020-01150-4), in which authors showed that mental resilience in 15.970 European participants, as an outcome of the perceived experiences and conceptualized as good mental health despite COVID-19 stressor, is mediated by the ability to easily recover from stress. Thereby, it is demonstrated that good stress response and positive appraisal, specifically of the consequences of the Corona crisis, are the strongest factors as compared to other psychological factors.”

Answer: Introduction has been corrected and a paragraph summarizing MS risk factors, pathogenesis, diagnosis and treatment has been added, the papers suggested by the reviewer has been included. A paragraph that better describes COVID-19 psycho-social effects has been added.

 

• Comment #7: “Materials and Methods:I suggest Authors to reorganize/rewrite this paragraph because, as it stands, it appears to be too much dispersive and describes the research procedures in an excessively broad way. I would ask the authors to clarify the criteria they decided to use for studies collection in their review: they should specify the number of studies included in the review and the requirements used to decide whether a study met the inclusion/exclusion criteria for the synthesis; they also should provide a more detailed description of all other variables for which data were sought (diagnostic criteria for COVID-19 infection and MS, information about vaccine, effects of COVID-19 vaccination on MS) and briefly present results of all statistical syntheses conducted.”

Answer: Materials and Methods section has been corrected according to the reviewers comment. This is a narrative review, and a systematic review of the literature including a meta-analysis of the variable is beyond the scope of the paper, so we regret to inform the reviewer that we didn’t perform a statistical analysis, but we added a paragraph in the discussion highlighting this limitation of the study.

 

• Comment #8: “Results: Please reorganize this section for clarity, providing full statistical information to ensure in-depth understanding and replicability of the findings. Also, please present statistical data in more detailed tables.

Answer: This is a narrative review, and a meta-analysis of the variable is beyond the scope of the paper, so we regret to inform the reviewer that we didn’t present a statistical analysis of the variables. This limitation has been discussed adding a paragraph in the discussion.

 

• Comment #9: ” Discussion: In my opinion, this review would be more compelling and useful to a broad readership if the authors moved beyond and discussed theoretical and methodological avenues in need of refinement, using this evidence to suggest a path forward. Technically, this manuscript focuses on different aspects of SARS-CoV-2 infection in pwMS, specifically on risks related to SARS-CoV-2 infection in MS. Still, I believe that it may be useful adding some evidence that showed the impact of COVID-19 on social behavior as well, focusing on the association between changes in social-distance levels and neural activation: a recent study showed how multisensory neurons in frontal and parietal areas, involved in representation of tactile information on the body and visual or auditory stimuli occurring in the personal space, support the capacity to read signals in the environment and action prediction, thus evoking modulation of autonomic arousal as a response to external stimuli (i.e., emotional stimuli) that appear in the peri-personal space, resulting in modulation of social distance (https://doi.org/10.1007/s00221-020-05829-4). In according with the previous point, to better characterize how COVID-19 perceived threat can affect behavioral expressions associated with distance from others, thus determining voluntary reduction of social interaction, I would recommend another interesting study. Here, authors analyzed how social distance can be modulated by arousing stimuli (i.e., emotional cues which can be interpreted as potentially threatening situations), and how this interpretation triggers a number of physiological responses that help regulating the distance between ourselves and others during social interaction (https://doi.org/10.1038/s41598-021-82223-2). Results from this research highlighted how context flexibly modulates interpersonal distance and how the current pandemic situation influences interpersonal distance evaluations overall.”

Answer: The discussion has been corrected and we added a paragraph discussing the effect of COVID-19 on neural networks of fear and peri-personal space and its relation-ship with social distancing. This is a very interesting point.

 

• Comment #10: “ I think the ‘Conclusions’ paragraph would benefit from some thoughtful as well as in-depth considerations by the authors, because as it stands, it lists down all the main findings of the research, without really stressing the theoretical significance of the study. Authors should make an effort, trying to explain the theoretical implication as well as the translational application of their research.”

Answer: Conclusion has been changed in order to describe the pragmatic implication of the literature review.

 

• Comment #11: “ In according to the previous comment, I would ask the authors to include a ‘Limitations and future directions’ section before the end of the manuscript, in which authors can describe in detail and report all the technical issues brought to the surface.”

Answer: the limitation of the study has been addressed in the discussion section.

 

• Comment #12: “Regarding theTables: please provide an explanatory caption for each table within the text.”

Answer: an explanatory caption has been added for each of the tables

 

• Comment #13: “References:Authors should consider revising the bibliography, as there are several incorrect citations. Indeed, according to the Journal’s guidelines, they should provide the abbreviated journal name in italics, the year of publication in bold, the volume number in italics for all the references.

Answer: References has been revised according to the indications

 

 

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

28 March 2022

Manuscript ID: neurolint-1621643

Type: Review

Title: “Multiple Sclerosis treatment in the COVID-19 era: a risk-benefit approach” by Immovilli P et al., submitted to Neurology International

Dear Authors,

The authors did an excellent work clarifying the questions I have raised in my previous round of review. Currently, this paper is a well-written, timely piece of research and provides an useful summary of the existing status of the potential risks of vulnerable people with multiple sclerosis (MS) being exposed to SARS-CoV-2.

The paper is well researched and nicely written, with a good balance between descriptive and narrative text. Nevertheless, I recommend using more evidence to back their claims. Thus, I recommend attempting to deepen the subject of their manuscript, as the bibliography remains too concise and, in my opinion, less than 50 articles for a literature review are really insufficient. Indeed, currently authors cite only 44 papers, and they are too low. Therefore, I suggest the authors to focus their efforts on researching more relevant literature: I believe that adding more studies and reviews will help them to provide better and more accurate background to this study.  Some of my minor suggestion to the authors are to further improve the theoretical background of the present article and its argumentation, by highlighting COVID-19 neurological effects: when discussing how SARS-CoV-2 modulates amygdala activation (lines 257-260), authors might also include a recent review (https://doi.org/10.3390/biomedicines10030627) in which authors focused on pathological mechanisms underlying altered emotion perception, which is especially impaired in brain-damaged patients, are related to amygdala and superior temporal sulcus dysfunctions. Furthermore, I also believe that a recent perspective manuscript on metabolic pathway (https://doi.org/10.17219/acem/139572) involved in the pathogenesis of a wide range of diseases might be of interest. This evidence might provide new insights on the impact that the COVID-19 pandemic has had on emotion perception, and therefore, regulation.

Overall, this is a timely and needed work, thus I believe that manuscript now meets the Journal’s standards for publication. I am always available for other reviews of such interesting and important articles. I look forward to seeing further study on this issue by these authors in the future.

Thank You for your work.

Best regards,

 

Reviewer

Author Response

We thank again the reviewer for the effort, which helped us to increase the quality of the paper. The citations has been increased up to 50 according to the suggestion, more relevant literature as been added in order to better explain the back ground of the study.

A further language revision has been made by a native English language professor with experience in medical writing.

 

 

Author Response File: Author Response.docx