COVID-19 Severity and Androgen Receptor Polymorphism
, Antonella Anzuini 2, Serena Bianchini 1, Luisa Caponecchia 3, Anna Carraro 4, Maria Rosa Ciardi 5, Fabiana Faja 1, Cristina Fiori 3, Daniele Gianfrilli 6, Andrea Lenzi 1, Miriam Lichtner 4, Claudio Maria Mastroianni 5, Patrizia Pasculli 5, Flavio Rizzo 6, Pietro Salacone 3, Annalisa Sebastianelli 3, Francesco Lombardo 1 and Donatella Paoli 1,*Round 1
Reviewer 1 Report
GENERAL COMMENT
The authors investigated the role of the CAG polymorphism as a possible responsible for the preparation of men to the more severe form of COVID-19 with a cross-sectional study on 142 patients.
Some major issues are present together with several minor issues.
MAJOR CORRECTIONS
I suggest to soften the conclusion in both abstract and main-text. The limitations of study are significant for strong conclusions.
The study was approved by the “Sapienza” Ethics Committee (Ref. 0282/2021). The ID is referred to 2021, therefore, theoretically, enrollment should have started in 2021. However, the study period is July 2020-January 2021. The authors should clarify this relevant concern.
Line 118: “Nasopharyngeal swab positive for SARS-CoV-2”. Were PCR or antigenic test performed? The authors should specify this point
Line 122: The authors should specify what “systemic diseases” means.
Line 130 (and other parts of text, figures and tables): I suggest to replace “mild” in “mild-to-moderate”
I suggest a brief section with the limitations of study
MINOR CORRECTIONS
Lines 28 and 41: I suggest to specify “androgen” receptor
I suggest to cite this interesting paper on COVID-19 https://pubmed.ncbi.nlm.nih.gov/34017152/
Figures: the authors should replace “,” with “.” to separate the decimals. Besides, the meanings of all acronyms should be specified in the legend of each figure
Author Response
Reviewer 1
GENERAL COMMENT
The authors investigated the role of the CAG polymorphism as a possible responsible for the preparation of men to the more severe form of COVID-19 with a cross-sectional study on 142 patients. Some major issues are present together with several minor issues.
MAJOR CORRECTIONS
Q1: I suggest to soften the conclusion in both abstract and main-text. The limitations of study are significant for strong conclusions.
A1: We thank the reviewer for his suggestion. We softened the conclusion, and we added a brief section with the limitation of study.
Q2: The study was approved by the “Sapienza” Ethics Committee (Ref. 0282/2021). The ID is referred to 2021, therefore, theoretically, enrollment should have started in 2021. However, the study period is July 2020-January 2021. The authors should clarify this relevant concern.
A2: We thank the reviewer for the possibility to clarify this point. We enrolled these patients “at least three months from recovery” (the first negative PCR test from a pharyngeal swab) during their follow up visits in the two participating Infectious Diseases departments. The enrolled patients actually had a “nasopharyngeal swab positive for SARS-CoV-2 between July 2020 and January 2021”. The first EC approval for the Rome center only is dated 14th September 2020 (Ref. 0646/2020). To increase the number of patients recruited, an amendment was requested and approved (the latest version of the EC approval is the one referred in the manuscript – 2nd April 2021 - Ref. 0282/2021) in order to include the Latina center. In both cases, in each center we started collecting blood samples for androgen receptor sequencing (and other study-related procedures) only after the corresponding EC approval.
Q3: Line 118: “Nasopharyngeal swab positive for SARS-CoV-2”. Were PCR or antigenic test performed? The authors should specify this point
A3: All diagnoses were based on RT-PCR. This has been clarified in the text.
Q4: Line 122: The authors should specify what “systemic diseases” means.
A4: We clarified in the manuscript this point.
Q5: Line 130 (and other parts of text, figures and tables): I suggest to replace “mild” in “mild-to-moderate”
A5: We agree with the reviewer. We modified this issue within the text.
Q6: I suggest a brief section with the limitations of study
A6: We thank the reviewer for this suggestion and we added a brief section with the limitation of our study within the text. “
MINOR CORRECTIONS
Q7: Lines 28 and 41: I suggest to specify “androgen” receptor
Q8: I suggest to cite this interesting paper on COVID-19 https://pubmed.ncbi.nlm.nih.gov/34017152/
Q9: Figures: the authors should replace “,” with “.” to separate the decimals. Besides, the meanings of all acronyms should be specified in the legend of each figure
A7-9: The text has been modified as requested.
Reviewer 2 Report
Interesting paper showing that the length of AR polyQ-repeats (CAG>23) as well as low levels of circulating testosterone support a more severe form of Covid-19. The paper is well written, data and conclusions are sound.
Suggestions:
As reduced AR-signalling predisposes men to a more severe from of Covid-19 the authors shoud discuss the implications of their findings for patients receiving androgen synthesis inhibitors and or/antiandrogens.
Author Response
Reviewer 2
Interesting paper showing that the length of AR polyQ-repeats (CAG>23) as well as low levels of circulating testosterone support a more severe form of Covid-19. The paper is well written, data and conclusions are sound.
Suggestions:
Q1: As reduced AR-signalling predisposes men to a more severe from of Covid-19 the authors should discuss the implications of their findings for patients receiving androgen synthesis inhibitors and or/antiandrogens.
A1: We thank the reviewer for his relevant suggestion. We added a short paragraph as requested.
Round 2
Reviewer 1 Report
The authors changed the paper according to my suggestions.
