P–097 The impact of SARS-CoV–2 on male gonadal function. A longitudinal study
Authors: Lauritsen M P , Leineweber T D , Hansen C B , Schneider U V , Westh H , Zedeler A , Cou. Freiesleben N L , Nielsen H S 
Published: August 2021

Abstract

Study question
Can severe acute respiratory syndrome coronavirus 2 (SARS-CoV–2) be detected in the semen of SARS-CoV–2 positive men, and does SARS-CoV–2 infection affect male reproductive function?

Summary answer
No SARS-CoV–2 RNA was detected in semen. An impact of SARS-CoV–2 infection on semen quality and reproductive hormone profile awaits evaluation at 3 + 6 months follow-up.

What is known already
SARS-CoV–2 may use angiotensin-converting enzyme (ACE)2 as an entry point into the cell. As ACE2 is expressed in testicular tissue, it has been speculated that SARS-CoV–2 may affect the male reproductive system. A cohort study including 38 male COVID–19 patients showed that SARS-CoV–2 was present in the semen of six patients (15.8%) [Li et al., 2020]. Later studies including a total of 223 patients have not provided evidence of transmission of SARS-CoV–2 via semen. There are to date no available longitudinal studies on semen quality following SARS-CoV–2 infection.

Study design, size, duration
Longitudinal cohort study including 50 non-hospitalized men from the general population in the Capital Region of Denmark. All participants had a confirmed SARS-CoV–2 infection by reverse-transcription polymerase chain reaction (RT-PCR) on oropharyngeal swab material within the last week. The presence of SARS-CoV–2 in semen samples by RT-PCR, semen parameters and reproductive hormone profile were assessed at inclusion and at 3 + 6 months follow-up. SARS-CoV–2 antibody levels were assessed 3–5 weeks after inclusion.

Participants/materials, setting, methods
SARS-CoV–2-positive males (age 18–60 years) were included. Oropharyngeal and semen samples were tested by RT-PCR applying the E-Sarbeco primers and probe published by Corman et al. 2020 and adapted to TaqMan Fast Virus 1-step master mix and LightCycler 480 as previously reported by Jørgensen et al. 2020. SARS-CoV–2 antibodies were detected using the serological immunoassay from Shenzhen YHLO Biotech on the iFlash 1800. Semen quality parameters were analysed according to World Health Organisation (WHO) standards.

Main results and the role of chance
To date, 25 men with a mean age of 35 years have been included in the study. SARS-CoV–2 RNA could not be detected in the semen samples of any of the 25 men at the time of inclusion. Twenty-one of the 25 men (84,0%) had a same day RT-PCR-confirmed SARS-CoV–2 infection in an oropharyngeal swab. RT-PCR cycle threshold (ct) values were distributed as follows: four (19,0%) were strongly positive (ct &lt; 25), 16 (76,2%) intermediately positive (ct 25–35) and one (4,8%) weakly positive (ct 35–45). The four men without PCR-confirmed SARS-CoV–2 infection all had a positive IgG response to SARS-CoV–2 at the time of inclusion. Longitudinal semen and reproductive hormone profiles analyses will be performed. Further studies are needed to prove whether SARS-CoV–2 can be transmitted to the male reproductive tract and whether SARS-CoV–2 infection may cause alterations of spermatogenesis and endocrine function.

Limitations, reasons for caution
Strengths of this study are the unselected population of men examined within a week after confirmed SARS-CoV–2 infection and the follow-up of semen parameters and endocrine profile. Limitations are the limited sample size and the fact that semen quality was not known before the participants were diagnosed with COVID–19.
Wider implications of the findings: Knowledge of viral detection and semen persistence of SARS-CoV–2 is essential for clinical practice and public health. There is a need for evidence-based counselling on the impact of SARS-CoV–2 infection for patients undergoing assisted reproduction technology and patients who have a need for semen cryopreservation.

Trial registration number
H–20027362