Monoclonal Antibodies as Potential COVID-19 Therapeutic Agents
Round 1
Reviewer 1 Report
This manuscript is a review about the potential use of monoclonal antibodies in COVID-19 therapy. The topic is certainly very interesting and discuss about new monoclonal antibodies which are still undergoing clinical trials, and the figure 1 is graphically well designed. Despite this, there are some conceptual and structural problems:
- There is already a review in the literature, which discuss the same topic in more detail, titled: Tackling COVID-19 with neutralizing monoclonal antibodies.
- Clinical and practical considerations about therapy with monoclonal antibodies are not explained in enough details considering the scope of the review.
- Casirivimab/Imdevimab even though are been withdrawn by FDA are still being widely used in other countries including Europe and thus their role in COVID-19 therapy should be discussed further;
- Tocilizumab is approved by EMA with specifics indications that are not mentioned;
- The paragraph about bamlanivimab/etesevimab and casirivimab/imdevimab should be discussed better and in more detail, like the authors did for Sotrovimab;
Author Response
Dear Sir or Madam,
Thank you kindly for your considerations. We have implemented all of your suggestions in our revision of the manuscript, to the best of our ability. We sincerely hope that you find the corrections sufficient to bring the manuscript up to a standard adequate for being published in COVID.
Listed below are our answers and revisions implemented in response to each provided comment:
POINT 1: "There is already a review in the literature, which discusses the same topic in more detail, titled: Tackling COVID-19 with neutralising monoclonal antibodies."
RESPONSE 1: The article in question, while in many ways similar to our manuscript, puts much emphasis on discussing the mechanisms of molecular action of anti-SARS-CoV-2 mAbs. Our manuscript is primarily focused on anti-SARS-CoV-2 mAb clinical trials and the clinical use of monoclonal antibodies, which constitutes a significant difference.
Even more importantly, the article in question was published in May of 2021 - which, as of now is 11 months ago, and before the emergence of the SARS-CoV-2 Omicron variant. Numerous developments have taken place in the field of anti-SARS-CoV-2 mAb research since then (such as the authorisations Evusheld and Bebtelovimab received from the EMA and FDA), which our review discusses comprehensively - especially having taken into account the considerations put forward by the reviewers.
POINT 2: "Clinical and practical considerations about therapy with monoclonal antibodies are not explained in enough details considering the scope of the review."
RESPONSE 2: Detailed explanations of a number of clinical and practical considerations such as direct risks and benefits for potential patients, the costs of mAb therapeutics, activity of mAb therapeutics against SARS-CoV-2 variants of concern, and the clinical utility of different mAb types have been added to the revised manuscript.
POINT 3: "Casirivimab/Imdevimab even though are been withdrawn by FDA are still being widely used in other countries including Europe and thus their role in COVID-19 therapy should be discussed further;"
RESPONSE 3: This combination of mAbs being approved by and used in countries other than the USA has been mentioned in the manuscript. The section describing casirivimab and imdevimab has been rewritten to emphasise this point, improve flow of the manuscript and add detail to the discussion of this mAb combination.
POINT 4: "Tocilizumab is approved by EMA with specifics indications that are not mentioned;"
RESPONSE 4: Added a section discussing the approval of tocilizumab by EMA.
POINT 5: "The paragraph about bamlanivimab/etesevimab and casirivimab/imdevimab should be discussed better and in more detail, like the authors did for Sotrovimab;"
RESPONSE 5: The sections discussing bamlanivimab/etesevimab and casirivimab/imdevimab have been rewritten to more closely adhere to the standard of the section discussing sotrovimab.
Thank you for your kind guidance and cooperation.
Sincerely,
Jacek Plichta
Reviewer 2 Report
Plichta et al. prepared a comprehensive review of monoclonal antibodies as COVID-19 therapeutic agents. The authors introduced the highlights and limitations of each type of COVID-19 therapy, each antibody, and each clinical trial. The authors also described the mechanism of how these antibodies fight SARS-CoV-2 and the challenges of developing mAbs for clinical use. The English language usage is clear and professional, and the manuscript is overall easy to follow. I therefore recommend it to be published in COVID after considering the following suggestions and making necessary revisions:
(1) The authors may consider keeping the advantages and limitations of each therapy/mAb/clinical trial in different paragraphs. In some sections of this manuscript, it reads like “advantage-limitation-advantage-limitation…(for example line 103–129)”, which may break the flow of the manuscript.
(2) Since the authors claimed that “convalescent plasma therapies remain costly”, it would be nice to provide evidence that the cost of monoclonal antibodies is lower, so it is superior to convalescent plasma therapy.
(3) Besides the detailed description of the clinical trial results of each antibody, the production (which is briefly discussed in Line 61–63), purification, yield, cost, and specificity of the monoclonal antibodies should be discussed in the main text.
(4) In Line 47–49, the authors mentioned that “Anti-SARS-CoV-2 neutralising monoclonal antibodies (mAbs) have the potential to become both therapeutic and prophylactic agents”. Upon reading the main text, it seems the authors did not comment on how the mAbs may be used as prophylactic agents. Those data should be provided.
(5) Line 178–180: the references about ADG–2 can be cited here, besides at the later place.
(6) Line 395–396: the references of the clinical trial in India should be cited here, besides at the later place.
Minor points:
(7) In general, please remember to have a space after period or comma.
(8) Line 42: “curative” is a less commonly used word; the authors may consider changing it.
(9) Line 173, Line 258: please add first-line indent.
Author Response
Dear Sir or Madam,
Thank you kindly for your considerations. We have implemented all of your suggestions in our revision of the manuscript, to the best of our ability. We sincerely hope that you find the corrections sufficient to bring the manuscript up to a standard adequate for being published in COVID.
Listed below are our answers and revisions implemented in response to each provided comment:
POINT 1: The authors may consider keeping the advantages and limitations of each therapy/mAb/clinical trial in different paragraphs. In some sections of this manuscript, it reads like “advantage-limitation-advantage-limitation…(for example line 103–129)”, which may break the flow of the manuscript.
RESPONSE 1: The descriptions of advantages and limitations of some therapies and mAbs have been reformatted and placed in separate paragraphs.
POINT 2: Since the authors claimed that “convalescent plasma therapies remain costly”, it would be nice to provide evidence that the cost of monoclonal antibodies is lower, so it is superior to convalescent plasma therapy.
RESPONSE 2: This claim has been removed, as mAb prices remain high, and the cost of convalescent plasma collection and treatment is difficult to estimate at a per-dose basis.
POINT 3: Besides the detailed description of the clinical trial results of each antibody, the production (which is briefly discussed in Line 61–63), purification, yield, cost, and specificity of the monoclonal antibodies should be discussed in the main text.
RESPONSE 3: The requested characteristics of many of the discussed antibodies have been added to the text. However not all of the mAbs discussed in the text are commercially available or have achieved approval by national health agencies. As such, no costs can be described for those mAbs.
POINT 4: In Line 47–49, the authors mentioned that “Anti-SARS-CoV-2 neutralising monoclonal antibodies (mAbs) have the potential to become both therapeutic and prophylactic agents”. Upon reading the main text, it seems the authors did not comment on how the mAbs may be used as prophylactic agents. Those data should be provided.
RESPONSE 4: Added a section on pre-exposure prophylactic usage of Evusheld, recently approved by EMA, MHRA and FDA (via EUA) in chapter 4.
POINT 5: Line 178–180: the references about ADG–2 can be cited here, besides at the later place.
RESPONSE 5: Added missing in-text citation.
POINT 6: Line 395–396: the references of the clinical trial in India should be cited here, besides at the later place.
RESPONSE 6: Added missing in-text citation.
POINT 7: In general, please remember to have a space after a period or comma.
RESPONSE 7: Fixed a number of punctuation errors.
POINT 8: Line 42: “curative” is a less commonly used word; the authors may consider changing it.
RESPONSE 8: Replaced/removed all instances of “curative” from the text.
POINT 9: Line 173, Line 258: please add first-line indent.
RESPONSE 9: Added missing indents.
Thank you for your kind guidance and cooperation.
Sincerely,
Jacek Plichta
Reviewer 3 Report
The manuscript is correctly prepared. It presents a wide range of information on the therapeutic use of monoclonal antibodies in COVID-19.
Below are some considerations:
- It is worth analyzing and summarizing the susceptibility to anti-SARS-CoV-2 monoclonal antibodies against different variants of the virus.
- It would be good to add information about bebtelovimab - in February, the FDA authorized this monoclonal antibody for the treatment of COVID-19 because it remains active against the Omicron variant.
- It would be good to add a chapter summarizing the direct benefits and risks for patients undergoing therapy.
- Chapter 4 lacks fluency in the narrative - some of the sentences resemble random interferences.
- The work should be carefully checked in terms of language and style.
Author Response
Dear Sir or Madam,
Thank you kindly for your considerations. We have implemented all of your suggestions in our revision of the manuscript, to the best of our ability. We sincerely hope that you find the corrections sufficient to bring the manuscript up to a standard adequate for being published in COVID.
Listed below are our answers and revisions implemented in response to each provided comment:
POINT 1: It is worth analysing and summarising the susceptibility to anti-SARS-CoV-2 monoclonal antibodies against different variants of the virus.
RESPONSE 1: Added a chapter (5) summarising the activity of anti-SARS-CoV-2 mAbs against variants of concern.
POINT 2: It would be good to add information about bebtelovimab - in February, the FDA authorised this monoclonal antibody for the treatment of COVID-19 because it remains active against the Omicron variant.
RESPONSE 2: Added a section about bebtelovimab and the FDA authorisation the mAb has received at the end of chapter 4.
POINT 3: It would be good to add a chapter summarising the direct benefits and risks for patients undergoing therapy.
RESPONSE 3: Added a chapter (9) on the direct benefits and risks for potential mAb therapy patients.
POINT 4: Chapter 4 lacks fluency in the narrative - some of the sentences resemble random interferences.
RESPONSE 4: Many sections of chapter 4 have been edited to improve text flow and establish a more cohesive narrative.
POINT 5: The work should be carefully checked in terms of language and style.
RESPONSE 5: The manuscript has been proofread thoroughly and a number of language and style errors have been eliminated.
Thank you for your kind guidance and cooperation.
Sincerely,
Jacek Plichta
