Effects of 2019 novel coronavirus on male reproductive system: a retrospective study

A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 April 2020 doi:10.20944/preprints202004.0280.v1

In addition to China, the number of confirmed cases in multiple overseas countries (Italy, Germany, Iran, South Korea, etc.) continues to increase every day, which has posed a serious threat to global public health security2. Although the mortality rate of COVID-19 is not as high as that of SARS-CoV, its incidence rate is higher and its infectivity is stronger. Therefore, effective control of the epidemic is particularly urgent and critical.
Since the outbreak of SARS in 2003, extensive structural analysis revealed the interaction between the spike protein receptor-binding domain (RBD) of SARS-CoV and the host cell receptor ACE2. 2019-nCoV is a kind of coronavirus highly similar to SARS-CoV; both of these viruses enter the host cell through a process mediated by their spike protein. Molecular simulation showed that the interaction between RBD and ACE2 of 2019-nCoV is stronger than that between RBD and ACE2 SARS-CoV, suggesting that ACE2 may play an important role in the process of 2019-nCoV entering host cells, which subsequently leads to infection3. A previous study showed possible testis damage in SARS patients and the effects of SARS-CoV on spermatogenesis.
These findings demonstrated that SARS-CoV may cause orchitis and extensive spermatogenic cell disruption4. Fan et al.5 found that ACE2 is highly expressed in the seminiferous tubules and Leydig cells of the testis, suggesting that the testis might be a potential target of virus attack.
In the present study, we first analyzed online datasets to investigate the expression of ACE2 in testis tissue, which is the potential target of abnormal spermatogenic function in patients infected with 2019-nCoV. We retrospectively University from January 2 to March 7, 2020, were enrolled. The exclusion criteria for the study were a history of varicocele, orchitis, testicular trauma, testicular torsion, vasectomy, cryptorchidism or testicular biopsy that may lead to testicular alterations. No informed consent was required because the data were anonymized. Renmin Hospital, located in Wuhan, is one of the major tertiary teaching hospitals of Wuhan University and is responsible for the treatment of severe COVID-19 patients.

Publicly available ACE2 expression dataset
In this research, we used an online dataset that was approved for public research. We investigated the organ distribution of ACE2 RNA and protein expression in human tissue on The Human Protein Atlas portal (Website: http://www.proteinatlas.org/)6. Meanwhile, immunohistochemistry (IHC) images of the testis were explored. Integrated HPA datasets were sourced from the Genotype-Tissue Expression (GTEx) project7. All data were available online.

Data Collection
The medical records of patients were retrospectively collected and analyzed by classified as severe COVID-19 because of the development of severe pneumonia, acute respiratory distress syndrome (ARDS) or organ dysfunction.
The median age of severe patients was higher than that of mild patients. In terms of age distribution, 86% of severe patients were more than 40 years old.
In the mild group, 90% of patients were less than 70 years old (  In this research, based on the organ distribution of ACE2 in human tissue revealed in online datasets, we found that the expression of ACE2 is relatively higher in the testis than in other organs and that ACE2 is mainly expressed in spermatogenic cells, suggesting that the testis may be potentially vulnerable to 2019-nCoV infection5,12. In addition to typical respiratory symptoms (cough and fever), some patients may experience other symptoms, such as diarrhea, headache, fatigue, and even a few patients do not develop symptoms13. In this study, we included In summary, front-line medical staff need to pay close attention to the testicular function of 2019-nCoV patients, especially for patients with future fertility requirements. Not only to pay attention to changes in the local symptoms and signs of the testis during the course of the disease but also to perform longterm follow-up of testicular spermatogenesis functional examination.

Conclusions
The online datasets indicated the potential impairment of the male reproductive system by 2019-nCoV. However, this group of cases suggested that male patients have few reproductive symptoms and signs, and 2019-nCoV was not present in the male reproductive system of patients with confirmed COVID-19.
In view of the potential impairment, the long-term follow-up for male COVID-19 patients with fertility needs is of great significance.