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Clinics of Surgery
Review Article Volume 4
ISSN 2638-1451
COVID-19 and Testis: A Systematic Review
Li B*
and Chai S#
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022,
China
*Corresponding author:
Bing Li,
Department of Urology, Union Hospital,
Tongji Medical College, Huazhong University
of Science and Technology,
Wuhan 430022, China,
Tel: +86 27 85351625,
Fax: +86 27 85726970,
E-mail: bingli@hust.edu.cn
Received: 04 Dec 2020
Accepted: 23 Dec 2020
Published: 28 Dec 2020
Copyright:
©2020 Li B et al. This is an open access article distribut-
ed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and
build upon your work non-commercially.
Citation:
Li B, COVID-19 and Testis: A Systematic Review. Clinics
of Surgery. 2020; 4(4): 1-2.
#
Author Contributions:
Chai S. These authors have contributed equally to this
article.
Keywords:
Corona Virus Disease 2019 (COVID-19); Severe
Acute Respiratory Syndrome Corona Virus 2
(SARS-CoV-2); Testis, Angiotensin-Converting
Enzyme 2 (ACE2)
1. Abstract
Corona Virus Disease 2019 (COVID-19), triggered by severe
acute respiratory syndrome corona virus 2 (SARS-CoV-2), has
created a global pandemic. As of November 20, 2020, SARS-
CoV-2 is known to have 56,623,643 persons infected globally,
and 1,355,963 deaths have been reported worldwide. Angioten-
sin-Converting Enzyme 2 (ACE2) has been found to be one of
the major receptors that modify the entry of SARS-CoV-2 into
human cells, and ACE2 is expressed in multiple organ systems
including the lungs, intestine, heart, kidney, and the testis. SARS-
CoV-2 has been detected in multiple organs. However, whether
the virus exists in the testis remains controversial. In this report we
looked at the SARS-CoV-2 test outcomes of semen samples from
COVID-19 male patients, we found that outcome was controver-
sial in different literature. We conclude that SARS-CoV-2 does not
exist in the test is most likely, but it causes damage to testicular
tissue instead.
2. Introduction
Since the discovery of COVID-19 caused by SARS-CoV-2 at the
end of December 2019, it has rapidly swept the world. As of No-
vember 20, 2020, there have been 56,623,643 confirmed cases
of COVID-2019, including 1,355,963 deaths, reported to WHO
(https://covid19.who.int/). When you read this article, the figures
would have changed to more threatening numbers, which indicates
that there are numerous male patients. SARS-CoV-2 cell entry de-
pends on ACE2 and TMPRSS2 [1], ACE2 is expressed in multiple
organ systems including type II alveolar cells of the lungs, intes-
tine, heart, kidney, and the test is [2]. SARS-CoV-2 has been de-
tected in multiple organs. However, whether the virus exists in the
testis remains controversial. Li et al [3] reported the presence of
SARS-CoV-2 in the semen samples while [4] and [5] detected oth-
erwise. In this report, we performed systematic review to evaluate
the presence of the SARS-CoV-2 in the testis and the possibility of
the impact of SARS-CoV-2 infection on male fertility.
3. Review
3.1. No SARS-CoV-2 Was Detected
Kate E. Stanley et al. [6] obtain an in-depth understanding of the
possible biologic consequences of SARS-CoV-2 infection on re-
production by observing the expression patterns of known viral
host entry proteins. Their results from scRNAseq data suggest that
sperm cells may not be exposed to the increased risk of viral entry
mediated by ACE2 and TMPRSS2, although there is no co expres-
sion in any testicular cell type, and they were unable to interrogate
Sertoli cells [6]. They [6] found moderate ACE2 expression in tes-
clinicsofsurgery.com 1
ticular tissue, whereas expression of TMPRSS2 was found to be
low or undetectable by bulk RNAseq and protein platforms. And
[4] also found ACE2 and TMPRSS2 are rarely expressed in the
human testes, with almost no overlapping gene expression in the
scRNA-seq dataset of human testicular cells at the University of
Utah, being consistent with.
Kate E. Stanley et al's study. Furthermore, [4] single-cell transcrip-
tome data suggested ACE2 RNA expression occurs at low levels
and they did not detect SARS-CoV-2 within semen of COVID-2019
patients, which indicates that SARS-CoV-2 would not be able to
gain entry to testicular cells through an ACE2/TMPRSS2-mediat-
ed mechanism. All semen samples of COVID-2019 patients were
negative for SARS-CoV-2 RNA and testicular samples from one
deceased COVID-2019 patient were negative in Song et al’s study
[7]. In other studies, semen and urine samples from an Italian man
were negative for SARS-CoV-2 RNA [8], and [5] did not detect
SARS-CoV-2 in semen samples of 23 COVID-2019 patients using
RT–qPCR.
3.2. SARS-CoV-2 Was Detected
Contrary to the above findings, SARS-CoV-2 was detected in se-
men samples of 6 COVID-2019 patients, while the remaining 32
semen samples were negative for SARS-CoV-2 RNA in Li et al’s
study [3]. However, we found that Li et al’s study did not describe
the semen collection or analysis in detail, nor excluded the pos-
sibility of viral contamination from non-semen sources, such as
urine of these patients. Through postmortem examination of the
testes from 12 COVID-19 patients, Yang et al. [9] found that one
case was positive for the virus in the test is, nine cases were nega-
tive for the virus in testicular tissue. They also performed electron
microscopy for three cases, and viral particles were not identified
in any case [9]. For the positive case, they considered that the tes-
ticular tissue sampled contained predominantly fibro vascular tis-
sue and very few seminiferous tubules. It is likely that RT-PCR de-
tected the virus present in blood rather than in testicular tissue [9].
3.3. SARA-CoV-2 Damage to Test Is
A study on testicular samples shows that severe acute respiratory
syndrome corona virus (SARS-CoV) has a significant impact on
the reproductive system [10]. Xu et al [10] observed the patholog-
ical changes of the testis in 6 patients who died from SARS and
compared them with the control group. They [10] found that SARS
caused orchitis. The testes are extensively destroyed and there are
few sperms in the seminiferous tubules. They also found that the
basement membrane of seminiferous tubules was thickened, with
obvious leukocyte infiltration and macrophage staining, which
suggests the influence of immune response on testis. However,
SARA-CoV was not detected in the affected testis. Yang et al. [9]
found that SARA-CoV-2 caused significant injury to Sertoli cells
and seminiferous tubules, and there was reduction of Leydig cells
and mild inflammatory infiltrates in the interstitium. The above
shows that SARS-CoV-2 cause orchitis and may lead to infertility.
4. Conclusion
As mentioned above, no strong evidence of SARS-CoV-2 in semen
of males COVID-19 patients, while COVID-19 can cause damage
to testis, suggesting that early intervention and treatment are need-
ed to avoid irreversible damage to the male reproductive system.
5. Acknowledgements
Financial disclosure: This work was supported by grant from the
National Natural Science Foundation of China (grant number
81671216, 81371379)
References:
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; 181: 271-80.
2. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al.,An-
giotensin-converting enzyme 2 is a functional receptor for the SARS
corona virus. Nature. 2003; 426: 450-4.
3. Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical Characteristics and
Results of Semen Tests Among Men With Coronavirus Disease
2019. JAMA network open. 2020; 3: e208292.
4. Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of
severe acute respiratory syndrome-coronavirus 2 in semen of males
recovering from coronavirus disease 2019. Fertility and sterility.
2020; 113: 1135-9.
5. Guo L, Zhao S, Li W, Wang Y, Li L, Jiang S, et al., Absence of
SARS-CoV-2 in semen of a COVID-19 patient cohort. Andrology.
2020.
6. Stanley KE, Thomas E, Leaver M, Wells D. Corona virus disease-19
and fertility: viral host entry protein expression in male and female
reproductive tissues. Fertility and sterility. 2020; 114: 33-43.
7. Song C, Wang Y, Li W, Hu B, Chen G, Xia P, et al., Absence of 2019
novel corona virus in semen and testes of COVID-19 patients†. Bi-
ology of reproduction. 2020; 103: 4-6.
8. Paoli D, Pallotti F, Colangelo S, Basilico F, Mazzuti L, Turriziani
O, et al., Study of SARS-CoV-2 in semen and urine samples of a
volunteer with positive naso-pharyngeal swab. Journal of endocri-
nological investigation. 2020; 43: 1819-22.
9. Yang M, Chen S, Huang B, Zhong JM, Su H, Chen YJ, et al., Patho-
logical Findings in the Testes of COVID-19 Patients: Clinical Impli-
cations. European urology focus. 2020; 6: 1124-9.
10. Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, et al. Orchitis: a com-
plication of severe acute respiratory syndrome (SARS). Biology of
reproduction. 2006; 74: 410-6.
clinicsofsurgery.com 2
Volume 4 Issue 4-2020 Review Article

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COVID-19 and Testis: A Systematic Review

  • 1. Clinics of Surgery Review Article Volume 4 ISSN 2638-1451 COVID-19 and Testis: A Systematic Review Li B* and Chai S# Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China *Corresponding author: Bing Li, Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China, Tel: +86 27 85351625, Fax: +86 27 85726970, E-mail: bingli@hust.edu.cn Received: 04 Dec 2020 Accepted: 23 Dec 2020 Published: 28 Dec 2020 Copyright: ©2020 Li B et al. This is an open access article distribut- ed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Citation: Li B, COVID-19 and Testis: A Systematic Review. Clinics of Surgery. 2020; 4(4): 1-2. # Author Contributions: Chai S. These authors have contributed equally to this article. Keywords: Corona Virus Disease 2019 (COVID-19); Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2); Testis, Angiotensin-Converting Enzyme 2 (ACE2) 1. Abstract Corona Virus Disease 2019 (COVID-19), triggered by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has created a global pandemic. As of November 20, 2020, SARS- CoV-2 is known to have 56,623,643 persons infected globally, and 1,355,963 deaths have been reported worldwide. Angioten- sin-Converting Enzyme 2 (ACE2) has been found to be one of the major receptors that modify the entry of SARS-CoV-2 into human cells, and ACE2 is expressed in multiple organ systems including the lungs, intestine, heart, kidney, and the testis. SARS- CoV-2 has been detected in multiple organs. However, whether the virus exists in the testis remains controversial. In this report we looked at the SARS-CoV-2 test outcomes of semen samples from COVID-19 male patients, we found that outcome was controver- sial in different literature. We conclude that SARS-CoV-2 does not exist in the test is most likely, but it causes damage to testicular tissue instead. 2. Introduction Since the discovery of COVID-19 caused by SARS-CoV-2 at the end of December 2019, it has rapidly swept the world. As of No- vember 20, 2020, there have been 56,623,643 confirmed cases of COVID-2019, including 1,355,963 deaths, reported to WHO (https://covid19.who.int/). When you read this article, the figures would have changed to more threatening numbers, which indicates that there are numerous male patients. SARS-CoV-2 cell entry de- pends on ACE2 and TMPRSS2 [1], ACE2 is expressed in multiple organ systems including type II alveolar cells of the lungs, intes- tine, heart, kidney, and the test is [2]. SARS-CoV-2 has been de- tected in multiple organs. However, whether the virus exists in the testis remains controversial. Li et al [3] reported the presence of SARS-CoV-2 in the semen samples while [4] and [5] detected oth- erwise. In this report, we performed systematic review to evaluate the presence of the SARS-CoV-2 in the testis and the possibility of the impact of SARS-CoV-2 infection on male fertility. 3. Review 3.1. No SARS-CoV-2 Was Detected Kate E. Stanley et al. [6] obtain an in-depth understanding of the possible biologic consequences of SARS-CoV-2 infection on re- production by observing the expression patterns of known viral host entry proteins. Their results from scRNAseq data suggest that sperm cells may not be exposed to the increased risk of viral entry mediated by ACE2 and TMPRSS2, although there is no co expres- sion in any testicular cell type, and they were unable to interrogate Sertoli cells [6]. They [6] found moderate ACE2 expression in tes- clinicsofsurgery.com 1
  • 2. ticular tissue, whereas expression of TMPRSS2 was found to be low or undetectable by bulk RNAseq and protein platforms. And [4] also found ACE2 and TMPRSS2 are rarely expressed in the human testes, with almost no overlapping gene expression in the scRNA-seq dataset of human testicular cells at the University of Utah, being consistent with. Kate E. Stanley et al's study. Furthermore, [4] single-cell transcrip- tome data suggested ACE2 RNA expression occurs at low levels and they did not detect SARS-CoV-2 within semen of COVID-2019 patients, which indicates that SARS-CoV-2 would not be able to gain entry to testicular cells through an ACE2/TMPRSS2-mediat- ed mechanism. All semen samples of COVID-2019 patients were negative for SARS-CoV-2 RNA and testicular samples from one deceased COVID-2019 patient were negative in Song et al’s study [7]. In other studies, semen and urine samples from an Italian man were negative for SARS-CoV-2 RNA [8], and [5] did not detect SARS-CoV-2 in semen samples of 23 COVID-2019 patients using RT–qPCR. 3.2. SARS-CoV-2 Was Detected Contrary to the above findings, SARS-CoV-2 was detected in se- men samples of 6 COVID-2019 patients, while the remaining 32 semen samples were negative for SARS-CoV-2 RNA in Li et al’s study [3]. However, we found that Li et al’s study did not describe the semen collection or analysis in detail, nor excluded the pos- sibility of viral contamination from non-semen sources, such as urine of these patients. Through postmortem examination of the testes from 12 COVID-19 patients, Yang et al. [9] found that one case was positive for the virus in the test is, nine cases were nega- tive for the virus in testicular tissue. They also performed electron microscopy for three cases, and viral particles were not identified in any case [9]. For the positive case, they considered that the tes- ticular tissue sampled contained predominantly fibro vascular tis- sue and very few seminiferous tubules. It is likely that RT-PCR de- tected the virus present in blood rather than in testicular tissue [9]. 3.3. SARA-CoV-2 Damage to Test Is A study on testicular samples shows that severe acute respiratory syndrome corona virus (SARS-CoV) has a significant impact on the reproductive system [10]. Xu et al [10] observed the patholog- ical changes of the testis in 6 patients who died from SARS and compared them with the control group. They [10] found that SARS caused orchitis. The testes are extensively destroyed and there are few sperms in the seminiferous tubules. They also found that the basement membrane of seminiferous tubules was thickened, with obvious leukocyte infiltration and macrophage staining, which suggests the influence of immune response on testis. However, SARA-CoV was not detected in the affected testis. Yang et al. [9] found that SARA-CoV-2 caused significant injury to Sertoli cells and seminiferous tubules, and there was reduction of Leydig cells and mild inflammatory infiltrates in the interstitium. The above shows that SARS-CoV-2 cause orchitis and may lead to infertility. 4. Conclusion As mentioned above, no strong evidence of SARS-CoV-2 in semen of males COVID-19 patients, while COVID-19 can cause damage to testis, suggesting that early intervention and treatment are need- ed to avoid irreversible damage to the male reproductive system. 5. Acknowledgements Financial disclosure: This work was supported by grant from the National Natural Science Foundation of China (grant number 81671216, 81371379) References: 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; 181: 271-80. 2. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al.,An- giotensin-converting enzyme 2 is a functional receptor for the SARS corona virus. Nature. 2003; 426: 450-4. 3. Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019. JAMA network open. 2020; 3: e208292. 4. Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertility and sterility. 2020; 113: 1135-9. 5. Guo L, Zhao S, Li W, Wang Y, Li L, Jiang S, et al., Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort. Andrology. 2020. 6. Stanley KE, Thomas E, Leaver M, Wells D. Corona virus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues. Fertility and sterility. 2020; 114: 33-43. 7. Song C, Wang Y, Li W, Hu B, Chen G, Xia P, et al., Absence of 2019 novel corona virus in semen and testes of COVID-19 patients†. Bi- ology of reproduction. 2020; 103: 4-6. 8. Paoli D, Pallotti F, Colangelo S, Basilico F, Mazzuti L, Turriziani O, et al., Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab. Journal of endocri- nological investigation. 2020; 43: 1819-22. 9. Yang M, Chen S, Huang B, Zhong JM, Su H, Chen YJ, et al., Patho- logical Findings in the Testes of COVID-19 Patients: Clinical Impli- cations. European urology focus. 2020; 6: 1124-9. 10. Xu J, Qi L, Chi X, Yang J, Wei X, Gong E, et al. Orchitis: a com- plication of severe acute respiratory syndrome (SARS). Biology of reproduction. 2006; 74: 410-6. clinicsofsurgery.com 2 Volume 4 Issue 4-2020 Review Article