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A small study of deceased nonvaccinated men who died of COVID-19 complications suggests the testes may be a sanctuary for the SARS-CoV-2 virus, raising questions about potential consequences for reproductive health among those infected.
The study, published online Tuesday on the preprint server MedRxiv, found that “patients who become critically ill exhibit severe damages and may harbor the active virus in testes,” which can “serve as a viral sanctuary.”
Guilherme M.J. Costa, PhD, a professor at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, led the study, which has not yet been peer-reviewed.
“A critical point of this article is that the virus was active in the patient’s testis after a long period of infection, indicating that the testis is able to maintain the viable virus for extended periods. It happens for many kinds of viruses in this genital organ,” Costa told Medscape Medical News.
Brian Keith McNeil, MD, vice-chair, Department of Urology at SUNY Downstate Health Sciences University in New York City, told Medscape Medical News the topic of COVID-19 and fertility has been discussed but data are sparse on the subject.
“The question this raises is whether or not COVID can live in the testes, and based on this it seems it can,” he said, adding that it also raises the question of whether COVID-19 could be transmitted through semen. “It leads one to wonder whether this could have a long-term impact on fertility in men and women.”
The authors write that deep testicular evaluation of patients who have been infected with COVID is critical because the testes have one of the highest expressions of angiotensin converting enzyme 2 (ACE2) receptors, which play a large role in entrance of the virus into cells.
“A direct influence of SARS-CoV-2 in testicular cells might deregulate ACE2, elevating the levels of angiotensin II, a potent pro-inflammatory and angiogenic peptide,” the authors write.
Sperm-Producing Cells Infected
In 2021, the researchers enrolled 11 male patients deceased from COVID-19 complications; none had received a COVID vaccine. Infection was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) performed during their hospital stay. All 11 patients were admitted to the intensive care unit with severe pulmonary symptoms.
All but one of the patients had children and none had scrotal symptoms or complaints during their time in the hospital. Their clinical histories revealed no testicular disorders.
Costa said they found that detecting SARS-CoV-2 mRNA in testes is difficult in a conventional RT-PCR test.
Therefore, “We modified the protocol of the RT-PCR and used nanosensors. We observed that SARS-CoV-2 has a huge tropism for the testes in this context,” he said.
Additionally, he said, the team performed stainings and “discovered that macrophages and germ cells are highly infected.”
That’s important, he said, because an immune cell, which is supposed to fight the virus, is infected in the tissue. Additionally, the germ cell, responsible for sperm production, is infected.
“This reopens the worries about the presence of SARS-CoV-2 in semen, as other authors mentioned,” he said.
The team also found that the testes are a good place for viral replication.
The authors say they are the first to show:
- The longer the severe condition, the lower the number of surviving germ cells
- There was fluctuation in several essential testicular genes
- The intratesticular testosterone levels are 30 times reduced in the testes of COVID-19 patients
The control group was composed of six patients who had undergone testicle removal after prostate cancer was suspected. Collection of both testicles from the test group was performed within 3 hours of death after a family member signed an informed consent document.
Researchers note that recent research on semen demonstrates that patients recovered from COVID-19 reestablish their sperm quality after 3 months of infection.
That study, in Fertility and Sterility , found that sperm quality was initially reduced for months in some men after recovery from COVID.
The team studied semen samples from 120 Belgian men (mean age, 35 years) at an average 52 days after their last COVID symptoms. The semen was not found to be infectious.
But among 35 men who provided samples within a month after infection, reductions in sperm motility were evident in 60% and sperm counts were reduced in 37%, according to the report.
The results [of the Costa et al paper] emphasize the importance of testicular damage in severe COVID-19,” Rafael Kroon Campos, PhD, a postdoctoral fellow in the Department of Microbiology & Immunology at The University of Texas Medical Branch at Galveston, told Medscape Medical News.
He noted that other viruses have also been shown to infect or otherwise cause testicular damage or orchitis, such as Zika, Ebola, and the closely related SARS-CoV-1. Sexual transmission has been documented for Zika and Ebola viruses.
Campos said with SARS-CoV-2, it is unclear whether sexual transmission plays a role.
“Some reports found evidence of viral RNA in semen, but these were rare occurrences. The study of Costa and colleagues used a combination of sensitive techniques and were able to detect a small amount of viral RNA and viral protein in the testicular tissue of the deceased patients, as well as show viral factories indicating replication of the virus by electron microscopy,” he said.
Campos said the findings are particularly important and concerning because of the large number of severe cases of COVID-19.
“It is critical to continue to investigate the impact of the disease in testes, including the impact of different variants of concern on testicular damage,” he said.
McNeil and Campos have disclosed no relevant financial relationships.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick
Créditos: Comité científico Covid