An analysis of the differential effect and the impact of SARS-CoV-2 infection on semen quality

By Neha MathurReviewed by Lily Ramsey, LLMJun 14 2023

In a recent study published in the eBioMedicine Journal, researchers performed a longitudinal observational cohort study among 120 males in Belgium.

The study aimed to analyze the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on semen quality parameters, including sperm concentration, motility, and morphology.

Study: SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients. Image Credit: Rost9/Shutterstock.com

Background

Studies have detected SARS-CoV-2 in the testis of deceased coronavirus disease 2019 (COVID-19) patients and even during the acute infection phase. Semen is uninfectious on average 21 days after SARS-CoV-2 infection; thus, the risk for sexual transmission of SARS-CoV-2 is low during this time window. 

However, due to a lack of longitudinal studies, short- and long-term effects of SARS-CoV-2 on sperm quality and subsequent effects on male fertility remain largely unknown.

Further, research has established that millions of meiotic reduction divisions occur in men daily, producing gametes even in an environment lacking immune protection; thus, male gametes are more susceptible to viral infections than female gametes. 

A perturbation in the meiotic reduction division during gametogenesis due to a viral infection momentarily ceases spermatozoa production, resulting in a compromised sperm concentration on average 43 days post-infection. Thus, another strategy is needed to protect or inactivate these gametes.

Moreover, in men, not only during sperm production but after sperm production, some viruses, e.g., the Zika virus, could gain access to the spermatozoa, which compromises the embryo.

A recent study showed that SARS-CoV-2's presence in the testis, even after recovery from COVID-19, could alter protein-coding genes in spermatozoa and transfer them to the embryo.

About the study

In the present study, researchers recruited males aged 18 to 70 who had confirmed COVID-19 in Belgium between March 2020 and June 2020 or August 2020 and February 2021.

Of 120 patients recruited in this study, 93, 42, nine, three, and two patients had two, three, four, five, and six control visits, of which 242 were post-COVID-19. During each follow-up visit, the team collected a fresh sperm and blood sample from each participant. Further, the team used the World Health Organization (WHO) criteria to assess sperm quality. They quantified the deoxyribonucleic acid (DNA) fragmentation index (DFI) and the high-density stainability (HDS), and IgA- and IgG-anti-sperm antibodies (ASA). 

For moving spermatozoa, the researchers used mixed antiglobulin reaction (MAR) tests to detect IgA and IgG. The team used light microscopy to determine the proportion of motile sperms with attached latex particles.

In addition, they recorded the location on the spermatozoan, head, midpiece, or tail, where the latex particles attached. The researchers tested all post-COVID-19 sperm samples for SARS-CoV-2 ribonucleic acid (RNA) with the SpermCOVID test, for which the detection limit was two SARS-CoV-2 RNA copies per ml.

They graded the motility of each spermatozoon into three categories, Grade A, B, and C, where the last category of sperm was immotile. While Grade A spermatozoa showed progressive motility and moved actively, linearly, or in a large circle, Grade B sperm swam in small circles but showed no progressive motility.

The synthesis of Apale-spermatogonia that become committed to meiosis and enter active spermatogenesis takes 16 days of the seminiferous epithelium cycle that constantly releases spermatozoa. Also, a spermatogenic wave lasts 74 days, followed by an epididymal transit that lasts 12 days. 

The researchers hypothesized that a perturbation in any of these processes due to SARS-CoV-2 infection would manifest as a reduced spermatozoa output that becomes apparent as a proportional difference between peak and bottom sperm concentration even after several days of COVID-19 onset.

This difference and other estimated sperm parameters served as a substitute when evaluating the impact of the SARS-CoV-2 infection on sperm parameters of all 93 patients who attended at least two follow-up visits.

The researchers calculated the time difference (in days) between the first SARS-CoV-2 positive reverse transcription-polymerase chain reaction (RT-PCR) (day zero) and the date of ejaculation on each of the 242 visits. They also determined, for each participant, the number of days post-infection when the sperm concentration was lowest or highest.

Furthermore, the researchers analyzed the effect of the SARS-CoV-2 infection across different rounds of spermatogenesis, totaling to 102-days. Finally, they calculated how many sperm parameters returned to normal, i.e., baseline values post-SARS-CoV-2 infection, and implicated these findings with the spermiogenesis cycle phase.

Results

Of all parameters, sperm concentration was dependent on the spermatogenic cycle. Recovery of the different sperm parameters varied between patients; however, it took more than one-year post-SARS-CoV-2 infection in some cases and depended on the patient's initial immune response. Also, peak progressive sperm motility post-COVID-19 depended on the patient's antibody response. However, the authors did not detect a decline in sperm concentration maxima during anytime post-COVID-19, further indicating that viral infection impacts the reduction division process. 

Every participant had a unique sperm production maximum, reflecting their efficiency in producing spermatocytes from spermatogonia. So, once the external influence declined, sperm concentrations returned to the maximum baseline value.

Patients producing both IgA/IgG-ASA had the fastest complete recovery, while patients without these antibodies could not completely recover. It could be due to a declining immunological response and its waning effect on spermatozoa.

Furthermore, the study data showed that fever did not reduce sperm concentration post-SARS-CoV-2 infection but the immune response afterward.

Perhaps IgA and IgG recognize the SARS-CoV-2 receptor angiotensin-converting enzyme-2 (ACE2); thus, they attached themselves to the spermatozoa tail where ACE2 was present.

Conversely, lethal sIgG-N in blood only correlated with higher DFI, consistent with reports that the antibodies are either protective or harmful.

In symptomatic COVID-19 patients who recovered, lowered hepatocyte growth factor (HGF) serum levels inhibited Apale-spermatogonia divisions, crossed the blood-testis barrier, and became spermatocytes, resulting in a lower sperm concentration.

For ejaculated spermatozoa between days zero and 43 post-infection, elevated HDS and DFI rendered the spermatozoa inactive.