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轻度2019冠状病毒病:一项关于严重急性呼吸综合征冠状病毒2在精液成分和细胞中的存在及其对精液参数影响的多中心前瞻性研究结果。

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.

作者信息

Bujan Louis, Mendeluk Gabriela, Mahé Dominique, Llabador Marie-Astrid, Bettiol Celia, Plotton Ingrid, Mansuy Jean-Michel, Delobel Pierre, Daudin Myriam, Moinard Nathalie, Ariagno Julia, Chenlo Patricia, Alvarez Muriel, Dejucq-Rainsford Nathalie, Pasquier Christophe

机构信息

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.

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.

出版信息

Andrology. 2025 Mar;13(3):544-554. doi: 10.1111/andr.13706. Epub 2024 Aug 2.

Abstract

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

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

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

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

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.

摘要

背景

严重急性呼吸综合征冠状病毒2是导致2019冠状病毒病的病毒,可影响多个器官。该病毒通过血管紧张素转换酶2和生殖器官中存在的宿主因子进入细胞,这引发了人们对精液中病毒脱落和生殖功能的担忧。

目的

研究轻度感染患者精液中的严重急性呼吸综合征冠状病毒2,识别精液中被感染的细胞,并探讨感染对性激素和精液参数的影响。

材料与方法

对54例轻度严重急性呼吸综合征冠状病毒2感染男性进行前瞻性研究。在症状出现后的7、15、30、60、90、180和365天收集精液,并检测血清、唾液、尿液和精液中的严重急性呼吸综合征冠状病毒2 RNA。使用Vero细胞培养评估精液中传染性严重急性呼吸综合征冠状病毒2的存在。通过针对严重急性呼吸综合征冠状病毒2核蛋白抗原和细胞标志物的免疫荧光鉴定被感染的精液细胞。测定精液特征以及睾酮、抑制素B、黄体生成素和卵泡刺激素水平。

结果

11%的患者至少有一次精液严重急性呼吸综合征冠状病毒2 RNA阳性。1例患者在感染发作后90天内精液中持续排出病毒,在第7天从精液中分离出具有复制能力的病毒,且细胞比例为40%。精子处理后,在第7天和第15天,90%的部分严重急性呼吸综合征冠状病毒2 RNA呈阳性。上游部分仅在第7天呈阳性。在精液中,核蛋白抗原主要在脱落的上皮细胞中检测到,在支持细胞中较少见。第30天的精子计数和活动精子计数低于第7天。急性期精液中的圆形细胞增多。在第7天和第15天,严重急性呼吸综合征冠状病毒2 RNA阳性精液的精子计数和活动精子计数低于阴性精液,而精液量和卵泡刺激素水平升高。长期随访显示,没有证据表明对激素或精液特征有不利影响。

讨论与结论

11%未住院的轻度2019冠状病毒病患者精液中有严重急性呼吸综合征冠状病毒2排出,其中1例患者持续了90天。未发现生殖细胞被病毒感染,但核蛋白抗原阳性的上皮精液细胞和支持细胞的检测提示生殖道感染。尽管不常见,但在急性期精液中可能含有具有复制能力的病毒,在性接触和辅助生殖过程中存在严重急性呼吸综合征冠状病毒2传播的潜在风险。轻度2019冠状病毒病对精子发生和生殖激素的影响是中度且可逆的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a88e/11867923/2ebbfea371e9/ANDR-13-544-g001.jpg

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