Androgen receptor polyQ alleles and COVID‐19 severity in men: A replication study
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Abstract
Background
Ample evidence indicates a sex‐related difference in severity of COVID‐19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID‐19 severity.
Objective
To test the association between the androgen receptor polyQ polymorphism and COVID‐19 severity in a large cohort of COVID‐19 male patients.
Materials and methods
This study included 1136 male patients infected with SARS‐CoV‐2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID‐19 severity was assessed by Chi‐squared (Chi 2 ) and logistic regression analysis.
Results
The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis).
Discussion
Androgen sensitivity may be a critical factor in COVID‐19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID‐19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID‐19 outcome.
Conclusions
The results obtained in our study do not support the role of this polymorphism as biomarker of COVID‐19 severity.
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SciScore for 10.1101/2022.03.25.22271678: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Fundación Jiménez Díaz Biobank, ref. PIC087-20; Clinical Research Ethics Committee Hospital Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca Biobank, ref.
Consent: Wherever possible, patients provided written or verbal informed consent to participate.Sex as a biological variable Subjects: This study included 1136 male patients from the STOP_Coronavirus cohort who were infected with SARS-CoV-2 as confirmed by positive PCR. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources PCA was performed using Plink software, version 1.9 (12). Plinksuggested: …SciScore for 10.1101/2022.03.25.22271678: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Fundación Jiménez Díaz Biobank, ref. PIC087-20; Clinical Research Ethics Committee Hospital Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca Biobank, ref.
Consent: Wherever possible, patients provided written or verbal informed consent to participate.Sex as a biological variable Subjects: This study included 1136 male patients from the STOP_Coronavirus cohort who were infected with SARS-CoV-2 as confirmed by positive PCR. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources PCA was performed using Plink software, version 1.9 (12). Plinksuggested: (PLINK, RRID:SCR_001757)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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