key: cord-345033-guisyj11 authors: Massarotti, Claudia; Garolla, Andrea; Maccarini, Elena; Scaruffi, Paola; Stigliani, Sara; Anserini, Paola; Foresta, Carlo title: SARS‐CoV‐2 in the semen: where does it come from? date: 2020-06-13 journal: Andrology DOI: 10.1111/andr.12839 sha: doc_id: 345033 cord_uid: guisyj11 A recent report by Li et al., described the presence of SARS‐CoV‐2 in semen samples of six patients, including two subjects who were recovering from the clinical disease. This finding re‐opened the discussion on possible male genital tract infection, virus shedding in semen, sexual transmission and safety of fertility treatments during the pandemic period [1]. As stated by the Authors themselves, the small sample size and short follow up dictate caution in the interpretation of their results. SARS-CoV-2 in the semen: where does it come from? 2 A recent report by Li et al., described the presence of SARS-CoV-2 in semen samples of six patients, 3 including two subjects who were recovering from the clinical disease. This finding re-opened the 4 discussion on possible male genital tract infection, virus shedding in semen, sexual transmission and 5 safety of fertility treatments during the pandemic period [1] . As stated by the Authors themselves, the 6 small sample size and short follow up dictate caution in the interpretation of their results. Moreover, 7 they tested semen samples for SARS-CoV-2 by qualitative RT-PCR, but neither the limits of detection 8 nor the threshold values were described [2] . Perhaps, the use of a quantitative PCR assay would be 9 more useful to detect the virus and to test its concentration in semen. Moreover, the semen 10 collection modality is not provided and a possible contamination with RNA fragments from hands or Accepted Article prostate. We know that multiple viruses can survive and actively replicate inside the prostate, 34 relatively sheltered from systemic therapies [11] . Regarding Coronaviruses, there is evidence that 35 MERS-CoV binds to the host cell receptor dipeptidyl peptidase 4 (DPP4), which is broadly expressed 36 on prostate cells [12] . We have no data on the presence of SARS-CoV-2 in the prostate, but we know 37 that TMPRSS2 is highly expressed by the epithelium of the human prostate and is androgen-38 responsive [13] . Moreover, even if ACE2 expression in the prostate is reported as "very low", the two 39 receptors are co-expressed in at least a small percentage of prostate hillock cells [5, 14] urines [17] . Since the distal urinary and reproductive tract are overlapping in males, the RNA detected 46 in semen could have been just a residual of urinary shedding. In conclusion, opening our prospective beyond the testis could be the key to better implications on 48 possible semen-related viral transmission as well as COVID19 short and long-term effect on male 49 reproductive function. Accepted Article Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease SARS-COV-2 presence in seminal fluid: myth or reality The novel angiotensinconverting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis Structure analysis of the receptor binding of 2019-nCoV Does COVID-19 affect male fertility? The ACE2 Expression in Sertoli cells and Germ cells may cause male reproductive disorder after SARS-CoV-2 Infection. OSF preprint Coronavirus disease (COVID-19) and fertility: viral host entry protein expression in male and female reproductive tissues TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention? Orchitis: a complication of severe acute respiratory syndrome (SARS) Replication of Zika Virus in Human Prostate Cells: A Potential Source of Sexually Transmitted Virus Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target -A Perspective 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 Accepted Article This article is protected by copyright. All rights reserved Expression of ACE2, the SARS-CoV-2 TMPRSS2 in Prostate Epithelial Cells Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection -clinicopathological and ultrastructural study Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues Detection of SARS-CoV-2 in Different Types of Clinical Specimens