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

Author:

Bujan Louis1ORCID,Mendeluk Gabriela2,Mahé Dominique3,Llabador Marie‐Astrid4,Bettiol Celia1,Plotton Ingrid5,Mansuy Jean‐Michel6,Delobel Pierre7,Daudin Myriam1,Moinard Nathalie1,Ariagno Julia2ORCID,Chenlo Patricia2,Alvarez Muriel7,Dejucq‐Rainsford Nathalie3,Pasquier Christophe6

Affiliation:

1. Institut National de la Santé et de la Recherche Médicale (Inserm) Développement Embryonnaire Fertilité Environnement (DEFE INSERM 1203) and CECOS, Service de Médecine de la Reproduction, Hôpital Paule de Viguier, CHU Toulouse Toulouse France

2. Laboratory of Male Fertility Buenos Aires University Clinical Hospital “José de San Martín”, INFIBIOC, Faculty of Pharmacy and Biochemistry, University of Buenos Aires Buenos Aires Argentina

3. Physiologie et Physiopathologie du Tractus Urogénital (Urgent) Université de Rennes, INSERM, Institut de Recherche en Santé, Environnement et Travail (Irset) Rennes France

4. Service de Biologie de la Reproduction, Hôpital Bichat AP‐HP Nord Paris France

5. Laboratoire de Biochimie et Biologie Moléculaire Hormonologie et Endocrinologie Moléculaire, Hospices Civils de Lyon Bron France

6. Laboratoire de Virologie Institut Fédératif de Biologie, CHU de Toulouse Toulouse France

7. Service des Maladies Infectieuses et Tropicales Hôpital Purpan, CHU Toulouse Toulouse France

Abstract

AbstractBackgroundSevere 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.ObjectivesTo 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 methodsProspective 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.Results11% 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 conclusion11% 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.

Funder

Merck Sharp and Dohme France

Publisher

Wiley

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