Semen Impairment and Occurrence of SARS-CoV-2 Virus in Semen After Recovery From COVID-19

M. Gacci; M. Coppi; E. Baldi; A. Sebastianelli; C. Zaccaro; S. Morselli; A. Pecoraro; A. Manera; R. Nicoletti; A. Liaci; C. Bisegna; L. Gemma; S. Giancane; S. Pollini; A. Antonelli; F. Lagi; S. Marchiani; S. Dabizzi; S. Degl'Innocenti F. Annunziato; M. Maggi; L. Vignozzi; A. Bartoloni; G.M. Rossolini; S. Serni

Disclosures

Hum Reprod. 2021;36(6):1520-1529. 

In This Article

Abstract and Introduction

Abstract

Study Question: How is the semen quality of sexually active men following recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection?

Summary Answer: Twenty-five percent of the men with recent SARS-Cov-2 infections and proven healing were oligo-crypto-azoospermic, despite the absence of virus RNA in semen.

What is Known Already: The presence of SARS-CoV-2 in human semen and its role in virus contagion and semen quality after recovery from coronavirus disease 2019 (COVID-19) is still unclear. So far, studies evaluating semen quality and the occurrence of SARS-CoV-2 in semen of infected or proven recovered men are scarce and included a limited number of participants.

Study Design, Size, Duration: A prospective cross-sectional study on 43 sexually active men who were known to have recovered from SARS-CoV2 was performed. Four biological fluid samples, namely saliva, pre-ejaculation urine, semen, and post-ejaculation urine, were tested for the SARS-CoV-2 genome. Female partners were retested if any specimen was found to be SARS-CoV-2 positive. Routine semen analysis and quantification of semen leukocytes and interleukin-8 (IL-8) levels were performed.

Participants/Materials, Setting, Methods: Questionnaires including International Index of Erectile Function and Male Sexual Health Questionnaire Short Form were administered to all subjects. The occurrence of virus RNA was evaluated in all the biological fluids collected by RT-PCR. Semen parameters were evaluated according to the World Health Organization manual edition V. Semen IL-8 levels were evaluated by a two-step ELISA method.

Main Results and the Role of Chance: After recovery from COVID-19, 25% of the men studied were oligo-crypto-azoospermic. Of the 11 men with semen impairment, 8 were azoospermic and 3 were oligospermic. A total of 33 patients (76.7%) showed pathological levels of IL-8 in semen. Oligo-crypto-azoospermia was significantly related to COVID-19 severity (P < 0.001). Three patients (7%) tested positive for at least one sample (one saliva; one pre-ejaculation urine; one semen and one post-ejaculation urine), so the next day new nasopharyngeal swabs were collected. The results from these three patients and their partners were all negative for SARS-CoV-2.

Limitations, Reasons for Caution: Although crypto-azoospermia was found in a high percentage of men who had recovered from COVID-19, clearly exceeding the percentage found in the general population, the previous semen quality of these men was unknown nor is it known whether a recovery of testicular function was occurring. The low number of enrolled patients may limit the statistical power of study.

Wider Implications of the Findings: SARS-CoV-2 can be detected in saliva, urine, and semen in a small percentage of men who recovered from COVID-19. One-quarter of men who recovered from COVID-19 demonstrated oligo-crypto-azoospermia indicating that an assessment of semen quality should be recommended for men of reproductive age who are affected by COVID-19.

Study Funding/Competing Interest(S): None.

Trial Registration Number: N/A.

Introduction

The world is currently experiencing the outbreak of coronavirus disease (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus exhibits a strong infectivity with a low virulence compared to previous coronavirus strains, and a higher fatality rate in men than in women (COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU), 2020). Widespread contact tracing followed by hospital isolation or quarantine is recommended to contain the outbreak (Swerdlow and Finelli, 2020).

Human-to-human transmission of SARS-CoV-2 usually occurs within households, including relatives and friends who are in intimate contact with symptomatic or incubating patients (Pan et al., 2020). In some patients, blood samples showed positive RT-PCR test results, suggesting that infection may be occasionally systemic (Wang et al., 2020). Respiratory droplets and physical contact of contaminated surfaces are the confirmed transmission modality of SARS-CoV-2 (Rothe et al., 2020), even if the virus has also been detected in saliva (To et al., 2020), teardrops, urine, and stool (Peng et al., 2020).

The occurrence of viral genomes in semen of infected men, previously not identified as being sexually transmitted, has been reported for Ebola and Zika (Feldmann, 2018). The high expression of angiotensin-converting enzyme (ACE) and transmembrane serine protease 2 (TMPRSS2) in somatic and germ cells of the testis suggests that SARS-CoV-2 virus may localize in the gonad (Wang and Xu, 2020). A recent study (Rastrelli et al., 2020) demonstrated the development of hypergonadotrophic hypogonadism in patients with active COVID-19 infection, suggesting an impairment of Leydig cell function, although whether this impairment is related to localization of the virus in the testis is unknown. However, in view of the essential role played by testosterone in spermatogenesis (Smith and Walker, 2014), alterations of semen quality in patients with COVID-19 can be hypothesized. In addition, semen parameters may be compromised by the inflammatory condition occurring in men with COVID-19.

Few studies have evaluated the presence of the virus in human semen. Paoli et al. reported the absence of SARS-CoV-2 RNA in semen and urine samples 13 days after COVID-19 diagnosis and 4 days after the second negative nasopharyngeal (NP) swab in a single patient who tested positive for SARS-CoV-2 through a NP-swab (PaoLi et al., 2020). Li et al. (2020) demonstrated that the semen of six patients tested positive for SARS-CoV-2, with four of these patients at the acute stage of infection and two at 2 and 3 days after clinical recovery, respectively. Pan et al. (2020) did not find viral RNA in any of 34 semen samples from males with active infection. Similarly, Song et al. (2020) demonstrated no detectable SARS-CoV-2 RNA in semen samples collected from 12 patients during the recovery phase: after 1–16 days from the second negative NP swab and 14–42 days after acute infection (Song et al., 2020). Only two studies (Guo et al., 2020; Ma et al., 2020) evaluated semen quality in a small cohort of men during infection or in the recovery phase of COVID-19.

In the present study, we investigated the direct (RNA) presence of SARS-CoV-2 in saliva, urine, and semen; evaluated semen parameters; and investigated semen IL-8 levels as a surrogate marker of the male genital tract inflammatory condition (Lotti et al., 2011) of 43 sexually active men with laboratory evidence of recovery from COVID-19.

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