No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019

Feng Pan, Xingyuan Xiao, Jingtao Guo, Yarong Song, Honggang Li, Darshan P Patel, Adam M Spivak, Joseph P Alukal, Xiaoping Zhang, Chengliang Xiong, Philip S Li, James M Hotaling, Feng Pan, Xingyuan Xiao, Jingtao Guo, Yarong Song, Honggang Li, Darshan P Patel, Adam M Spivak, Joseph P Alukal, Xiaoping Zhang, Chengliang Xiong, Philip S Li, James M Hotaling

Abstract

Objective: To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle.

Design: Observational, cross-sectional study.

Setting: Tertiary referral center.

Patient(s): Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples.

Intervention(s): None.

Main outcome measure(s): Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets.

Result(s): Six patients (19%) demonstrated scrotal discomfort suggestive of viral orchitis around the time of COVID-19 confirmation. Severe acute respiratory syndrome-CoV-2 was not detected in semen after a median of 31 days (interquartile range, 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression.

Conclusion(s): Severe acute respiratory syndrome-CoV-2 was not detected in the semen of patients recovering from COVID-19 1 month after COVID-19 diagnosis. Angiotensin-converting enzyme 2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.

Keywords: COVID-19; angiotensin-converting enzyme 2; coronavirus; infertility; male; semen.

Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Expression of ACE2 and TMPRSS2 in human testicular cells using single-cell RNA-seq dataset. (A) Dimension reduction (t-SNE) analysis of single-cell transcriptome data from human testes (n = 6,490) based on data from Guo et al. (10). Each dot represents a single cell and is colored according to its cluster identity, as indicated on the figure key. (B) Expression patterns of ACE2 and TMPRSS2 projected on the t-SNE plot. Red indicates high expression, and gray indicates low or no expression, as shown on the figure key. (C) Scatter plot to show the co-expression of ACE2 (x-axis) and TMPRSS2 (y-axis) in human testicular cells.

References

    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 doi: 10.1001/jama.2020.2648.
    1. The Center for Systems Science and Engineering, Johns Hopkins. Coronavirus COVID-19 Global Cases. 2020. Available at:
    1. Wang W., Xu Y., Gao R., Lu R., Han K., Wu G., et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020 doi: 10.1001/jama.2020.3786.
    1. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454.
    1. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273.
    1. Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 doi: 10.1016/j.cell.2020.02.052.
    1. Chen Y.W., Lee M.S., Lucht A., Chou F.P., Huang W., Havighurst T.C., et al. TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells. Am J Pathol. 2010;176:2986–2996.
    1. Zhao S., Zhu W., Xue S., Han D. Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol. 2014;11:428–437.
    1. Guo J., Nie X., Giebler M., Mlcochova H., Wang Y., Grow E.J., et al. The dynamic transcriptional cell atlas of testis development during human puberty. Cell Stem Cell. 2020;26:262–276.e4.
    1. Guo J., Grow E.J., Mlcochova H., Maher G.J., Lindskog C., Nie X., et al. The adult human testis transcriptional cell atlas. Cell Res. 2018;28:1141–1157.
    1. Liu W., Han R., Wu H., Han D. Viral threat to male fertility. Andrologia. 2018;50
    1. Salam A.P., Horby P.W. The breadth of viruses in human semen. Emerging Infect Dis. 2017;23:1922–1924.
    1. Xu J., Qi L., Chi X., Yang J., Wei X., Gong E., et al. Orchitis: a complication of severe acute respiratory syndrome (SARS) Biol Reprod. 2006;74:410–416.
    1. Douglas G.C., O'Bryan M.K., Hedger M.P., Lee D.K., Yarski M.A., Smith A.I., et al. The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology. 2004;145:4703–4711.
    1. Liu Y., Yan L.M., Wan L., Xiang T.X., Le A., Liu J.M., et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis. 2020 doi: 10.1016/s1473-3099(20)30232-2.

Source: PubMed

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