Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19

Background The presence of severe acute respiratory syndrome coronavirus 2 (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. Recent reports evidence that, after SARS-CoV-2 infection, male reproductive function and semen quality may be damaged. Aim To evaluate the semen parameters and inflammation of sexually active men following recovery from SARS-CoV-2 infection at 1 month and 3 months follow-up after the second negative nasopharyngeal swab. Materials and methods A prospective cross-sectional study on sexually active men recovered from SARS-CoV-2 infection was performed. For previously hospitalized COVID-19 patients, data on serum inflammatory markers were retrospectively collected. One month after the second SARS-CoV-2 negative nasopharyngeal swab and 3 months later, four biological fluid samples, namely saliva, pre-ejaculation urine, semen, and post-ejaculation urine, were collected. The occurrence of SARS-CoV-2 RNA in the specimen was evaluated in all the biological fluids collected by RT-PCR. Female partners were retested if any specimen was found to be SARS-CoV-2 positive. Semen parameters were evaluated according to the World Health Organization manual edition V. Furthermore, semen inflammation was assessed by quantification of semen leukocytes and interleukin-8 (IL-8) levels and evaluation of a panel of sperm cytokine levels by a two-step ELISA method. Results A total of 43 men were enrolled in the study. 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 3 patients and their partners were all negative for SARS-CoV-2. At 1-month follow-up, 25% of the men with recent SARS-Cov-2 infections and proven healing were oligo-cryptoazoospermic, despite the absence of virus RNA in semen. Of the 11 men with semen impairment, 8 were azoospermic and 3 were oligospermic. Serum inflammatory markers (procalcitonin and C-reactive protein) were analyzed in previously hospitalized patients both at admission and at peak of infection. Levels at admission were statistically significantly higher in patients resulting in crypto-azoospermic with respect to those resulting in normozoospermic (p = 0.05;p = 0.03 and p = 0.02, respectively) after healing. Oligo-crypto-azoospermia was significantly related to COVID-19 severity (P < 0.001). A total of 33 patients (76.7%) showed pathological levels of IL-8 in semen. Interleukin-1β and tumor necrosis factor-α levels were significantly negatively related to sperm total number and concentration, whereas interleukin-4 was correlated with sperm motility. At 3-months follow-up, 8/10 men with semen impairment showed an overall increase of semen parameters compared to levels assessed after 1 month. Of the 4 crypto-/azoo-spermic men 1 month after healing, 2 resulted oligozoospermic, 1 normozoospermic and only 1 remained azoospermic. Two of the 3 oligozoospermic men turned normozoozpermic. Semen cytokine levels remained elevated after 3 months, except for IL-6. Discussion and conclusion SARS-CoV-2 can be detected in saliva, urine, and semen in a small percentage of men who recovered from COVID-19. 25% of men who recovered from COVID-19 demonstrated oligo-crypto-azoospermia. Negative correlations between interleukin-1β and tumor necrosis factor-α and sperm number and the overall high levels of semen cytokines indicate a potential detrimental role of SARS-CoV-2 driven inflammation on spermatogenesis. An overall tendency to an improvement of semen parameters was found although a genital tract inflammatory condition appears to persist at least 3 months after COVID-19 recovery. Despite the low number of enrolled patients may limit the statistical power of study and the fact that the previous semen quality of these men was unknown, our results indicate that male of reproductive age recovering from COVID-19 deserve accurate follow-up for their fertility status.

Safety issues in semen banks during the COVID-19 pandemic: data from a European survey.

PURPOSE: We performed a survey among European semen banks enquiring safety protocols during the COVID-19 pandemic. We report the experience from a center searching SARS-CoV-2 mRNA in semen of patients undergoing cryopreservation from May 2020 to January 2021. METHODS: A questionnaire was submitted to accredited semen banks of the European Academy of Andrology (EAA) and the Italian Society of Andrology and Sexual Medicine (SIAMS). A total of 22 centers answered to the survey. SARS-CoV-2 mRNA in semen was evaluated by RT-PCR in 111 subjects banking in the Semen Bank of Careggi University Hospital (Florence, Italy). RESULTS: No particularly drastic safety measures were adopted by the majority of the centers to prevent the risk of contamination or transmission of the virus. The most common strategy (77.3%) was the administration of an anamnestic questionnaire. About half of the centers request a negative nasopharyngeal swab (NPS) before cryopreservation. Few centers use a quarantine tank, in case of late response of NPS, and only 4 store in a dedicated tank in case of infection. SARS-CoV-2 mRNA was not found in 111 semen samples cryopreserved in the Florentine bank. CONCLUSIONS: European semen banks use different measures to handle semen samples for cryopreservation during COVID-19 pandemic. The request of NPS is advised to better manage couples undergoing ART and to protect the personnel operating in the bank/ART center. Finally, due to the areas of uncertainties of an almost unknown virus, it is absolutely recommended the use of safe devices for sample handling and storage.

P0142 Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19

Introduction & Objectives: The presence of SARS-CoV-2 in human semen and its role in virus transmission and semen quality after recovery from coronavirus disease 2019 (COVID-19) is still undefined. To date, studies evaluating semen quality and the occurrence of SARS-CoV-2 in semen of infected or proven recovered men are scarce and include a limited number of cases. Aim of this study is to evaluate the semen quality of sexually active men following recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Materials & Methods: A prospective cross-sectional study on sexually active men who were known to have recovered from SARS-CoV2 was performed, after Ethical Appraisal (ClinicalTrials.gov Identifier: NCT04446169). Four biological fluid samples, specifically saliva, pre-ejaculation urine, semen and post-ejaculation urine, were tested for the SARS-CoV-2 genome by RT-PCR. Routine semen parameters and quantification of semen leukocytes and interleukin-8 (IL-8) levels were evaluated according to the World Health Organization manual edition V and by a two-step ELISA method respectively. Questionnaires including International Index of Erectile Function and Male Sexual Health Questionnaire Short Form were administered to all subjects. Results: From 326SARS-CoV-2 positive male patients, 160 (49%) we re eligible.Amongthem,117were excluded, 55 because werenotreachable by phone, 46 refused to participate and other 16 were unable to collect semen samples. Therefore, 43 patients were finally enrolled. Among them. 3 patients (7%) tested positive for at least one sample (1 saliva;1 pre-ejaculation urine;1 semen and 1 post-ejaculation urine),so the day after new nasopharyngeal swabs were collected. The results from these three patients and their partners were all negative for SARS-CoV-2. Overall, 25% of the men studied were oligo-crypto-azoospermic after recovery from COVID-19. 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). Conclusions: 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 showing that an evaluation of semen quality should be recommended for men of reproductive age who are affected by COVID-19.

Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19.

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.