key: cord-324800-l8xl4g2a
authors: Eisenberg, Michael L.
title: Coronavirus Disease 2019 (COVID-19) and men’s reproductive health
date: 2020-04-22
journal: Fertil Steril
DOI: 10.1016/j.fertnstert.2020.04.039
sha: 
doc_id: 324800
cord_uid: l8xl4g2a

nan

As the COVID-19 pandemic rages across the world, the scientific community continues to study the pathophysiology of SARS-Cov-2 virus to guide transmission, susceptibility, and treatment. A respiratory infection, the disease is known to lead to the expected symptoms including fever, cough, shortness of breath, etc (1). A highly contagious virus, SARS-Cov-2 is detected in the nasal secretions, sputum, feces, rarely blood (1%) of infected individuals but not in the urine (2) . While cardiac, ocular, and neurologic symptoms of the COVID-19 have been reported, the reproductive implications of coronavirus infection remain unknown. As reports document higher rates of infection, morbidity, and mortality among male patients, attention has shifted to potential male genetic susceptibility. Scientists have identified the main path for coronavirus entry into the cell -namely via the viral spike (S) protein attaching to the Angiotensin Converting Enzyme 2 (ACE2) and employing the cellular serine protease (TMPRSS2) for S protein priming both of which are known to be present in the testis (3). Thus concern has arisen regarding 1) infection of the testes and 2) possible sexual transmission.

In the current report, Pan and colleagues address these separate but related questions regarding the possible testicular manifestations of COVID-19 (4). Among the thirty-four men studied, no detectable SARS-Cov-2 by RT-PCR was identified in the semen. This is a reassuring fact regarding possible (or lack there of) viral transmission. However, it is important to note that the men studied were often several weeks removed from acute infections and many had only mild symptoms, so it is conceivable that earlier time points or higher viral loads may lead to different results. But given the normal time course of semen turnover, that appears less likely.

Given the known mechanisms of SARS-Cov-2 entry into cells and the requirement for dual expression of ACE and TMPRSS2 proteins, the authors used their existing single cell RNA seq cellular data to show that only 4 of 6490 (<0.1%) testicular cells contain RNA for both proteins. Thus it appears unlikely that SARS-Cov-2 can enter into any cells in the testis (e.g. germ cells, Leydig cells, Sertoli cells, etc) as has been hypothesized.

Next, the authors reported another interesting and novel clinical observation, namely that 17.6% (6/34) of men reported scrotal discomfort at the time of Covd-19 infection. Previously symptoms of COVID-19 center on stigmata of severe systemic or respiratory illness. This novel scrotal observation should be confirmed but may improve future screening and should be further studied to understand the pathophysiology as well as the reproductive sequelae in men. Indeed, the current report was not able to assess any changes in semen quality among the participants thus it remains unknown how and if the fecundability of infected men is impaired. Prior data from other febrile illnesses have demonstrated that acute illness and elevated body temperatures (i.e. fevers) can temporarily lower spermatogenesis. Whether COVID-19 follows this model, remains to be elucidated. In addition, as more than 80% of those who are infected by the coronavirus are asymptomatic, the reproductive implications for these men would likely be favorable but also remains unknown.

Nevertheless, the current report represents the first exploration of the association between SARS-Cov-2 and human fecundability. How women are affected and consequences to assisted and unassisted reproduction in the face of acute COVID-19 infection or recovery remains to be studied. But given the current impact of the pandemic on the world, the likelihood the virus will remain for some time, and that over 100 million babies are born every year, the reproductive implications of SARS-Cov-2 should be further studied.

Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

No evidence of SARS-CoV-2 in semen of males recovering from COVID-19