COVID-19 Damages Male Fertility, and for a Long Time

As much as an infected person would like to think that they are done with COVID-19 once the test turns negative, the reality is often different. For many people, problems such as muscle weakness and brain fog can linger for months after the infection is cleared. While I’m fascinated by the long-term neurological impacts of COVID-19 (that might be another blog post), today, we are going to explore something else: Does COVID-19 affect fertility? The picture is not clear for women yet, so we will focus on men for now.

Can the virus infect the cells of the testes or the sperm?

SARS-CoV-2, the coronavirus behind the disaster of COVID-19, uses a receptor called ACE2 to enter into cells. If a particular cell type expresses this receptor, the virus can potentially infect it. ACE2 is indeed expressed in testes, and its expression is age-dependent¹. Men in their 30s appear to have the highest amount of this protein². What about sperm cells? Although they express some ACE2, they don’t usually have TMPRSS2 alongside it^3,4. TMPRSS2 is an enzyme that helps the virus enter the cell. The virus can efficiently infect if ACE2 and TMPRSS2 are present together. Because the cells don’t have those two simultaneously, scientists consider it unlikely that SARS-CoV-2 would directly infect testicular cells and sperms. There is also no evidence, as of yet, suggesting that the virus can be transmitted sexually.

Don’t celebrate yet. There are other ways for the virus to hurt your sperm.

One way the coronavirus could impact fertility is by directly infecting the reproductive cells, but we’ve already established that this is unlikely. There are a few more ways, though. The virus could affect the production of hormones that regulate reproduction. There are indeed reports of abnormal secretion of sexual hormones in COVID-19 patients⁵. Also, the systemic inflammation caused by the virus can negatively affect the testes and the health of the sperm. As an immunologist, I obviously want to focus on the inflammation-related possibility.

There is a physical barrier between the developing sperm cells and the surrounding blood vessels called the blood-testis barrier (BTB). This barrier is essential for the immune-privileged environment that the sperms need. However, when there is unusual inflammation, it might disrupt the BTB. This negatively affects sperm function and, consequently, fertility.

Multiple studies reported inflammation-related damage to the testes from the autopsies of deceased COVID-19 patients^6-8. One of those studies also reported high levels of inflammatory proteins in the semen of COVID-19 patients compared to healthy controls⁷. Interestingly, these studies did not encounter any virus in the testes. This further strengthens the idea that the damage to the male reproductive system is a secondary consequence of inflammation rather than a direct infection of reproductive cells. Fever, caused by the inflammatory response to infections, is already known to negatively impact sperm quality temporarily. But are the effects of COVID-19 also temporary? Or should we worry?

The adverse effects last for at least 2 months.

Researchers from Germany and Iran have just published a study exploring COVID-19’s effects on male fertility in a longer period than studied so far⁹. They followed 84 people infected with SARS-CoV-2 and 105 healthy controls for 2 months and took samples every 10 days. The semen of the recovered COVID-19 patients had higher levels of inflammation markers and reactive oxygen species. They also contained more markers of cell death. The bad news doesn’t stop there. The patient group had less semen volume, fewer sperm cells, decreased ability of the sperms to move, and structural abnormalities in the sperm. These significant changes all persisted over the course of the study.

More studies investigating even longer time periods are needed to understand exactly how long fertility is impaired. Still, it is clear that the infection damages male reproductive ability, at least for a few months. So, if you are a recovered COVID-19 patient and planning to have a baby, you might want to wait a bit. In time, it would be clearer how the health of the sperm cells is affected and how that might impact the health of the offspring. Let’s hope that further studies show reproductive functions eventually recover. We really don’t need another aspect of our lives turned upside-down by this virus.

Sources

1. Liu, Xixi, et al. “Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes.” Science China Life Sciences 63.7 (2020): 1006-1015.
2. Shen, Qiaoyan, et al. “The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS‐CoV‐2 infection.” Journal of Cellular and Molecular Medicine 24.16 (2020): 9472-9477.
3. Pan, Feng, et al. “No evidence of severe acute respiratory syndrome–coronavirus 2 in semen of males recovering from coronavirus disease 2019.” Fertility and sterility 113.6 (2020): 1135-1139.
4. Stanley, Kate E., et al. “Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues.” Fertility and sterility 114.1 (2020): 33-43.
5. Ma, Ling, et al. “Evaluation of sex‐related hormones and semen characteristics in reproductive‐aged male COVID‐19 patients.” Journal of medical virology 93.1 (2021): 456-462.
6. Duarte-Neto, Amaro N., et al. “Pulmonary and systemic involvement in COVID-19 patients assessed with ultrasound-guided minimally invasive autopsy.” Histopathology 77.2 (2020): 186-197.
7. Li, Honggang, et al. “Impaired spermatogenesis in COVID-19 patients.” EClinicalMedicine 28 (2020): 100604.
8. Yang, Ming, et al. “Pathological findings in the testes of COVID-19 patients: clinical implications.” European urology focus 6.5 (2020): 1124-1129.
9. Maleki, Behzad H., et al. “COVID-19 and male reproductive function: a prospective, longitudinal cohort study.” Reproduction (2021): Epub ahead of print.