SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study

Abstract

The ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment. Currently, adverse events associated with immunizations have raised some degree of concern, irrespective of its huge benefits in dealing with disease severity and decreasing mortality and morbidity. This hitherto study evaluates histological changes in rats’ testes, epididymis, prostate, and seminal vesicles and analyzes hormone levels after solely N protein inoculation. Therefore, we exposed a group of Lewis rats to weekly injections of the recombinant N protein for 28 days, while a control group was inoculated with a buffer solution. The N group revealed a more significant number of spermatozoa. Spermatozoa in the seminiferous tubules were counted in twenty 400 × microscopy fields (mean of 9.2 vs. 4.6 in the control group; p < 0,01), but significantly lower testosterone levels (mean of 125.70 ng/dl vs. 309,00 ng/dl in the control group; p < 0,05) were found. No other histological and biochemical changes were displayed. Conclusively, these data suggest testicular hormonal imbalance mediated by the SARS-CoV-2 N protein that could be linked to reported post-COVID-19 syndrome hypogonadism. More relevant research might be performed to confirm this viral antigen’s deleterious mechanism in the human testicular microenvironment, particular in Leydig cell function.

Systematic analyses of the factors influencing sperm quality in patients with SARS-CoV-2 infection

“…This highlights the complexity of male hormone level regulation. Interestingly, in another study by Jorge Hallak 50 and colleagues, inoculation of the SARS-CoV-2 nucleocapsid protein into the testes, epididymis, prostate, and seminal vesicles of rats did not show significant histological changes. However, the treated group exhibited higher sperm counts and lower testosterone levels, while LH levels did not change significantly.…”

Comprehensive evaluation of inactivated SARS-CoV-2 vaccination on sperm parameters and sex hormones

“…In an experimental study, Carrasco et al. found that the serum T levels in rats inoculated with the isolated N protein were significantly lower than those in the control group ( 44 ). Compared to healthy men, COVID-19 patients were accompanied by elevated serum LH levels and reduced T/LH ratios, suggesting possible subclinical impairment of male gonadal function ( 45 , 46 ).…”

Urological complications of COVID-19: a systematic review

“…Teixeira et al ( 74 ) suggest that a decreased testosterone/luteinizing hormone ratio correlated with high levels of C-reactive protein and white blood cell count, reported by some authors, can mean a transient stage of hypogonadism. In an experimental study, Carrasco et al ( 75 ) inoculated in rats nucleocapsid protein, that have high IgG antibodies against it in COVID-19 patients and found low serum levels of testosterone and free testosterone in these rats compared with a control group. They suggest that this hormone imbalance can be linked with a post-COVID-19 syndrome hypogonadism.…”