What Is New in Prophylaxis and Treatment of COVID-19 in Renal Transplant Patients? A Report from an ESOT Meeting on the Topic
Round 1
Reviewer 1 Report
The work to be reviewed gives an overview of treatment and prophylaxis for Covid-19 in transplanted patients. It has the format of a narrative review and has a broad scope. There is no description of any literature search methodology. The abstract is quite poorly written and requires extensive language modifications. The main body of the text is written with somewhat better English but also needs some work before attaining a level more suitable for publication.
The biggest issue with this work is the lack of any attempt at a systematic review. The areas covered in the paper have matured, and a large number of publications are available, often with varying findings. A narrative review does not add anything to the literature as a whole. References are provided inconsistently - eg. on page 3 line 63-65 the paper refers to multiple studies but provides no references. Table 1 is simply borrowed from Liefelt's study but not referenced in the Table itself. Table 2 is also just borrowed in a similar way. This kind of borrowing of tables provides the reader with no new insights or analyses. Many studies are mentioned in the following text, but it is not always clear is the study population were transplanted patients or the general population. This study would benefit from a stated search methodology and from tables that include results, population and methods, amongst other things.
The section on monoclonal antibodies and antivirals would also benefit from a clear search methodology and a table to show component study characteristics and results. Table 3 has the same problem as Tables 1 and 2.
The conclusion has many claims with no references. Without data, these are just opinions and should be relegated to the "Letters" section. The conclusion speaks of "effective protection" - but no data is provided on what this might be for recent variants. RBD thresholds, specific-NAb thresholds? It states vaccination should be avoided for 3 months after Tx. Because of poor response or because it introduces risks. Should it be avoided or repeated with a shorter interval? Any data?
Author Response
Please see the attachment
Author Response File: Author Response.docx
Reviewer 2 Report
Dear authors,
I was very interested of your review WHAT IS NEW IN PROPHYLAXIS AND TREATMENT OF COVID- 19 IN RENAL TRANSPLANT PATIENTS? as this category of patients have a week immune system.
Here are my suggestions regarding the present manuscript:
The manuscript is well documented, and the chapters chosen to reflect the need of kidney transplant recipients.
The references are well chosen, and the review is well balanced.
To the guidelines by the French Society of Pharmacology and Therapeutics should be added other existing guidelines.
Beside the data from Centers for Disease Control and Prevention. COVID data tracker. 2022. Available at: 763 https://covid.cdc.gov/covid-data-tracker. Accessed 21 July 2022, I believe more data worth to be added.
There are also some minor grammar mistakes.
Author Response
Please see the attachment
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
1. There is still no literature search methodology described, as would be desirable in a proper review. The paper claims to be a report from an ESOT meeting on Covid-19 prevention and treatment. If so, the paper could benefit from having this information reflected in the title.
2. The abstract has not been perceptibly improved. I think it is important to mention that this paper is a report from an ESOT meeting and not a formal review of the topic(s).
3. The new references are noted. Ref 50-52 are found both in text and in a table legend. Legends should be able to stand alone. Consider using author names as well as ref numbers in the tables/legends.
4. See pt 3
5. This is an improvement
6. This is adequately improved
7. I found no new information on threshold values. By this, I mean the value at which the patient is likely to be protected from clinical disease. This was relatively low up until the delta variant but most papers I have seen show very high values for Omikron.
8. This is adequately improved
9. My point is that you should specify in the paper whether it is due to a likely lower response or a risk of adverse events. In our experience it is the former. This reasoning is important when informing clinical judgements on a case-by-case basis.
Author Response
Second response to reviewer 1
Point 1 The paper claims to be a report from an ESOT meeting on COVID 19 prevention and treatment. If so, the paper could benefit from having this information reflected in the title
Response 1 The title has been accordingly modified.
Point 2 Is important to mention that this paper is a report from an ESOT meeting and not a formal review
Response 2 The abstract has been furtherly improved and the suggestion has been inserted
Response 3 Consider using author names as well as ref numbers in the tables /legends
Response 3 This has been done for the mentioned tables
Point 7 No information on threshold values
Response 7 A specific paragraph has been added with three more references
Protective values of RBD IgG and Neutralizing Antibodies, Their interrelationship and factors influencing their levels.
In a first study by Dimeglio et at (14) 8758 healthy people were studied and followed by time. Approximately half of them received one or two doses of vaccine. Considering NA, a titer of 64 to 128 gave 94% protection and a titer of 256 provided a full protection. Considering RBD IgG , a concentration between 141 and 1700 binding antibody units (BAU/ml) provided 89.3% of protection and a full protection was provided by BAU/ml > 1700.
The study refers to healthy people and to wild type or delta SARS-CoV-2.
In a further study, Dimeglio et al (15) considered the protective values after the emergency of Omicron BA.1 and BA.2). They analyzed 259 healthy subjects after vaccination. NA titer of 64 to 128 gave 78.4% protection respect to 94% protection obtained for delta variant. Levels of BAU/ml as high as 20,000 provided only 87.7% protection.
A study from Suntronwong et al (16) found a strong correlation between the binding and neutralizing antibodies after third dose vaccination.
Almost all the studies documented a decline over time of the antibody levels and, as expected transplanted patients had significantly lower levels even after vaccination.
Point 9 Specify in the paper whether it is due to a likely lower response
Response 9 This has been clearly specified in the text
Time after transplantation has an important role on the immune response, because in the early period the higher immunosuppression and the higher incidence of rejection rate may prevent or reduce the immune response.
Reviewer 2 Report
I am satisfied with the review.
Author Response
Thank you