Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs
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Abstract
The novel coronavirus SARS-CoV2 has been observed to cause a higher incidence and greater severity of disease in males, as seen in multiple cohorts across the globe. The reasons for gender disparity in disease severity is unclear and can be due to host factors. To determine whether males have delayed viral clearance after infection, we evaluated the time to clearance in symptomatic patients tested by serial oropharyngeal/nasopharyngeal swabs followed by RT-PCR at a reference lab in Mumbai, India. A total of 68 subjects with median age of 37 years (3-75 range) were examined and included 48 (71%) males and 20 (29%) females. We observed that females were able to achieve viral clearance significantly earlier than males, with a median difference of 2 days in achieving a negative PCR result (P value = 0.038). Furthermore, examination of 3 families with both male and female patients followed serially, demonstrated that female members of the same household cleared the SARS-CoV2 infection earlier in each family. To determine reasons for delayed clearance in males, we examined the expression patterns of the SARS-CoV2 receptor, Angiotensin-converting enzyme 2 (ACE2), in tissue specific repositories. We observed that the testes was one of the highest sites of ACE2 expression in 3 independent RNA expression databases (Human Protein Atlas, FAMTOM5 and GETx). ACE2 was also determined to be highly expressed in testicular cells at the protein levels. Interestingly, very little expression of ACE2 was seen in ovarian tissue. Taken together, these observations demonstrate for the first time that male subjects have delayed viral clearance of SARS-CoV2. High expression of ACE2 in testes raises the possibility that testicular viral reservoirs may play a role in viral persistence in males and should be further investigated.
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SciScore for 10.1101/2020.04.16.20060566: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The clinical protocol was IRB approved by the Kasturba Hospital for Infectious Diseases Institutional Review Board on April 7, 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable A log rank test was used to compare the difference in viral clearance between males and females and is represented in Figure 1. Table 2: Resources
No key resources detected.
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 …SciScore for 10.1101/2020.04.16.20060566: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The clinical protocol was IRB approved by the Kasturba Hospital for Infectious Diseases Institutional Review Board on April 7, 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable A log rank test was used to compare the difference in viral clearance between males and females and is represented in Figure 1. Table 2: Resources
No key resources detected.
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.
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SciScore for 10.1101/2020.04.16.20060566: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Methods: The clinical protocol was IRB approved by the Kasturba Hospital for Infectious Diseases Institutional Review Board on April 7, 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Abstract The novel coronavirus SARS-CoV2 has been observed to cause a higher incidence and greater severity of disease in males, as seen in multiple cohorts across the globe. Table 2: Resources
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).
About SciScore
SciScore is an automated tool that …
SciScore for 10.1101/2020.04.16.20060566: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Methods: The clinical protocol was IRB approved by the Kasturba Hospital for Infectious Diseases Institutional Review Board on April 7, 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Abstract The novel coronavirus SARS-CoV2 has been observed to cause a higher incidence and greater severity of disease in males, as seen in multiple cohorts across the globe. Table 2: Resources
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).
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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