Mild coronavirus disease 2019: Results of a multicentric prospective study on severe acute respiratory syndrome coronavirus 2 presence in semen fractions and cells and its effects on semen parameters.
COVID‐19
SARS‐CoV‐2
male genital tract
male reproductive function
reproductive biology
semen
seminal cells
sexual transmission risk
shedding
virus semen
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
revised:
18
06
2024
received:
03
04
2024
accepted:
06
07
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
2
8
2024
Statut:
aheadofprint
Résumé
Severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019, affects multiple organs. The virus enters cells through angiotensin-converting enzyme-2 and host factors present in genital organs, leading to concern over virus shedding in semen and reproductive function. To investigate severe acute respiratory syndrome coronavirus 2 in semen from patients with a mild infection, identify the seminal infected cells, and explore the effect of the infection on sex hormones and semen parameters. Prospective study of 54 men with mild severe acute respiratory syndrome coronavirus 2 infection. Semen was collected at 7, 15, 30, 60, 90, 180, and 365 days after symptom onset, and severe acute respiratory syndrome coronavirus 2 RNA was measured in serum, saliva, urine, and semen. The presence of infectious severe acute respiratory syndrome coronavirus 2 in semen was assessed using Vero cell culture. Infected semen cells were identified using immunofluorescence against severe acute respiratory syndrome coronavirus 2 nucleoprotein antigen and cell markers. Semen characteristics as well as testosterone, inhibin B, luteinizing hormone, and follicle-stimulating hormone levels were determined. 11% of patients had at least one severe acute respiratory syndrome coronavirus 2 RNA-positive semen. One patient had viral semen shedding up to day 90 after infection onset, with replication-competent virus isolated from semen and 40% cell fraction at day 7. After sperm preparation, 90% fraction was severe acute respiratory syndrome coronavirus 2 RNA-positive at days 7 and 15. The swim-up fraction was positive only on day 7. In semen, nucleoprotein antigen was detected mainly in exfoliated epithelial cells and less frequently in Sertoli cells. Sperm count and motile sperm count were lower at day 30 than at day 7. Round cells in semen were increased during the acute phase. At days 7 and 15, sperm count and motile sperm count were lower in severe acute respiratory syndrome coronavirus 2 RNA-positive semen compared with negative semen, while semen volume and follicle-stimulating hormone levels were increased. Long-term follow-up shows no evidence of a detrimental effect on hormonal or semen characteristics. 11% of patients with mild coronavirus disease 2019 who were not hospitalized had severe acute respiratory syndrome coronavirus 2 excretions in semen, which persisted for up to 90 days in one patient. No germ cells appeared infected by the virus, but the detection of nucleoprotein antigen-positive epithelial semen cells and Sertoli cells suggests genital tract infection. Albeit infrequent, semen may contain the replication-competent virus during the acute phase with potential risk of severe acute respiratory syndrome coronavirus 2 transmissions during sexual contact and assisted reproduction procedures. The effect of mild coronavirus disease 2019 on spermatogenesis and reproductive hormones was moderate and reversible.
Sections du résumé
BACKGROUND
BACKGROUND
Severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus disease 2019, affects multiple organs. The virus enters cells through angiotensin-converting enzyme-2 and host factors present in genital organs, leading to concern over virus shedding in semen and reproductive function.
OBJECTIVES
OBJECTIVE
To investigate severe acute respiratory syndrome coronavirus 2 in semen from patients with a mild infection, identify the seminal infected cells, and explore the effect of the infection on sex hormones and semen parameters.
MATERIALS AND METHODS
METHODS
Prospective study of 54 men with mild severe acute respiratory syndrome coronavirus 2 infection. Semen was collected at 7, 15, 30, 60, 90, 180, and 365 days after symptom onset, and severe acute respiratory syndrome coronavirus 2 RNA was measured in serum, saliva, urine, and semen. The presence of infectious severe acute respiratory syndrome coronavirus 2 in semen was assessed using Vero cell culture. Infected semen cells were identified using immunofluorescence against severe acute respiratory syndrome coronavirus 2 nucleoprotein antigen and cell markers. Semen characteristics as well as testosterone, inhibin B, luteinizing hormone, and follicle-stimulating hormone levels were determined.
RESULTS
RESULTS
11% of patients had at least one severe acute respiratory syndrome coronavirus 2 RNA-positive semen. One patient had viral semen shedding up to day 90 after infection onset, with replication-competent virus isolated from semen and 40% cell fraction at day 7. After sperm preparation, 90% fraction was severe acute respiratory syndrome coronavirus 2 RNA-positive at days 7 and 15. The swim-up fraction was positive only on day 7. In semen, nucleoprotein antigen was detected mainly in exfoliated epithelial cells and less frequently in Sertoli cells. Sperm count and motile sperm count were lower at day 30 than at day 7. Round cells in semen were increased during the acute phase. At days 7 and 15, sperm count and motile sperm count were lower in severe acute respiratory syndrome coronavirus 2 RNA-positive semen compared with negative semen, while semen volume and follicle-stimulating hormone levels were increased. Long-term follow-up shows no evidence of a detrimental effect on hormonal or semen characteristics.
DISCUSSION AND CONCLUSION
CONCLUSIONS
11% of patients with mild coronavirus disease 2019 who were not hospitalized had severe acute respiratory syndrome coronavirus 2 excretions in semen, which persisted for up to 90 days in one patient. No germ cells appeared infected by the virus, but the detection of nucleoprotein antigen-positive epithelial semen cells and Sertoli cells suggests genital tract infection. Albeit infrequent, semen may contain the replication-competent virus during the acute phase with potential risk of severe acute respiratory syndrome coronavirus 2 transmissions during sexual contact and assisted reproduction procedures. The effect of mild coronavirus disease 2019 on spermatogenesis and reproductive hormones was moderate and reversible.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Merck Sharp and Dohme France
Informations de copyright
© 2024 The Author(s). Andrology published by John Wiley & Sons Ltd on behalf of American Society of Andrology and European Academy of Andrology.
Références
Xu J, He LT, Zhang Y, et al. Severe acute respiratory syndrome coronavirus 2 and male reproduction: relationship, explanations, and clinical remedies. Front Physiol. 2021;12:651408. doi:10.3389/fphys.2021.651408
Shirbhate E, Pandey J, Patel VK, et al. Understanding the role of ACE‐2 receptor in pathogenesis of COVID‐19 disease: a potential approach for therapeutic intervention. Pharmacol Rep. 2021;73(6):1539‐1550. doi:10.1007/s43440‐021‐00303‐6
Dai P, Qiao F, Chen Y, et al. SARS‐CoV‐2 and male infertility: from short‐ to long‐term impacts. J Endocrinol Invest. 2023;46(8):1491‐1507. doi:10.1007/s40618‐023‐02055‐x
Song H, Seddighzadeh B, Cooperberg MR, Huang FW. Expression of ACE2, the SARS‐CoV‐2 receptor, and TMPRSS2 in prostate epithelial cells. Eur Urol. 2020;78(2):296‐298. doi:10.1016/j.eururo.2020.04.065
Xu J, Qi L, Chi X, et al. Orchitis: a complication of severe acute respiratory syndrome (SARS). Biol Reprod. 2006;74(2):410‐416. doi:10.1095/biolreprod.105.044776
Le Tortorec A, Matusali G, Mahe D, et al. From ancient to emerging infections: the Odyssey of viruses in the male genital tract. Physiol Rev. 2020;100(3):1349‐1414. doi:10.1152/physrev.00021.2019
Mahe D, Bourgeau S, Frouard J, et al. Long‐term Zika virus infection of non‐sperm cells in semen. Lancet Infect Dis. 2020;20(12):1371. doi:10.1016/S1473‐3099(20)30834‐3
Entezami F, Samama M, Dejucq‐Rainsford N, Bujan L. SARS‐CoV‐2 and human reproduction: an open question. EClinicalMedicine. 2020;25:100473. doi:10.1016/j.eclinm.2020.100473
Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw Open. 2020;3(5):e208292. doi:10.1001/jamanetworkopen.2020.8292
Delaroche L, Bertine M, Oger P, et al. Evaluation of SARS‐CoV‐2 in semen, seminal plasma, and spermatozoa pellet of COVID‐19 patients in the acute stage of infection. PLoS One. 2021;16(12):e0260187. doi:10.1371/journal.pone.0260187
Saylam B, Uguz M, Yarpuzlu M, Efesoy O, Akbay E, Cayan S. The presence of SARS‐CoV‐2 virus in semen samples of patients with COVID‐19 pneumonia. Andrologia. 2021;53(8):e14145. doi:10.1111/and.14145
Gacci M, Coppi M, Baldi E, et al. Semen impairment and occurrence of SARS‐CoV‐2 virus in semen after recovery from COVID‐19. Hum Reprod. 2021;36(6):1520‐1529. doi:10.1093/humrep/deab026
Machado B, Barra GB, Scherzer N, et al. Presence of SARS‐CoV‐2 RNA in semen‐cohort study in the United States COVID‐19 positive patients. Infect Dis Rep. 2021;13(1):96‐101. doi:10.3390/idr13010012
Purpura LJ, Alukal J, Chong AM, et al. SARS‐CoV‐2 RNA shedding in semen and oligozoospermia of patient with severe coronavirus disease 11 weeks after infection. Emerg Infect Dis. 2022;28(1):196‐200. doi:10.3201/eid2801.211521
Calvet GA, Kara E, Gonsalves L, et al. Viral shedding of SARS‐CoV‐2 in body fluids associated with sexual activity: a systematic review and meta‐analysis. BMJ Open. 2024;14(2):e073084. doi:10.1136/bmjopen‐2023‐073084
Wang S, Zhang A, Pan Y, et al. Association between COVID‐19 and male fertility: systematic review and meta‐analysis of observational studies. World J Mens Health. 2023;41(2):311‐329. doi:10.5534/wjmh.220091
Hu B, Liu K, Ruan Y, et al. Evaluation of mid‐ and long‐term impact of COVID‐19 on male fertility through evaluating semen parameters. Transl Androl Urol. 2022;11(2):159‐167. doi:10.21037/tau‐21‐922
Depuydt C, Bosmans E, Jonckheere J, et al. SARS‐CoV‐2 infection reduces quality of sperm parameters: prospective one year follow‐up study in 93 patients. EBioMedicine. 2023;93:104640. doi:10.1016/j.ebiom.2023.104640
Lauritsen MP, Kristensen TL, Hansen CB, et al. The impact of acute SARS‐CoV‐2 on testicular function including insulin‐like factor 3 (INSL3) in men with mild COVID‐19: a longitudinal study. Andrology. 2023. doi:10.1111/andr.13494
World Health Organization. Laboratory Manual for the Examination and Processing of Human Semen. World Health Organization; 2010.
Bujan L, Daudin M, Matsuda T, et al. Factors of intermittent HIV‐1 excretion in semen and efficiency of sperm processing in obtaining spermatozoa without HIV‐1 genomes. AIDS. 2004;18(5):757‐766. doi:10.1097/00002030‐200403260‐00006
Pourquet A, Teoli J, Bouty A, et al. Steroid profiling in the amniotic fluid: reference range for 12 steroids and interest in 21‐hydroxylase deficiency. J Clin Endocrinol Metab. 2023;108(5):e129‐e138. doi:10.1210/clinem/dgac656
Matusali G, Houzet L, Satie AP, et al. Zika virus infects human testicular tissue and germ cells. J Clin Invest. 2018;128(10):4697‐4710. doi:10.1172/JCI121735
Paoli D, Pallotti F, Nigro G, et al. Molecular diagnosis of SARS‐CoV‐2 in seminal fluid. J Endocrinol Invest. 2021;44(12):2675‐2684. doi:10.1007/s40618‐021‐01580‐x
Bujan L, Mansuy JM, Hamdi S, Pasquier C, Joguet G. 1 year after acute Zika virus infection in men. Lancet Infect Dis. 2020;20(1):25‐26. doi:10.1016/S1473‐3099(19)30678‐4
Mansuy JM, Suberbielle E, Chapuy‐Regaud S, et al. Zika virus in semen and spermatozoa. Lancet Infect Dis. 2016;16(10):1106‐1107. doi:10.1016/S1473‐3099(16)30336‐X
Yang M, Chen S, Huang B, et al. Pathological findings in the testes of COVID‐19 patients: clinical implications. Eur Urol Focus. 2020;6(5):1124‐1129. doi:10.1016/j.euf.2020.05.009
Mahe D, Bourgeau S, da Silva J, et al. SARS‐CoV‐2 replicates in the human testis with slow kinetics and has no major deleterious effects ex vivo. J Virol. 2023;97(10):e0110423. doi:10.1128/jvi.01104‐23
Edimiris P, Doehmen C, Muller L, et al. Mild COVID‐19 has no detrimental effect on semen quality. Basic Clin Androl. 2023;33(1):15. doi:10.1186/s12610‐023‐00190‐2
He YF, Wang J, Ren JL, Zhao YB, Chen J, Chen XJ. Effect of COVID‐19 on male reproductive system—a systematic review. Front Endocrinol. 2021;12:677701. doi:10.3389/fendo.2021.677701
Pallotti F, Esteves SC, Faja F, et al. COVID‐19 and its treatments: lights and shadows on testicular function. Endocrine. 2023;79(2):243‐251. doi:10.1007/s12020‐022‐03221‐6
Paoli D, Pallotti F, Anzuini A, et al. Male reproductive health after 3 months from SARS‐CoV‐2 infection: a multicentric study. J Endocrinol Invest. 2023;46(1):89‐101. doi:10.1007/s40618‐022‐01887‐3