Association between COVID-19 status and Leydig cell functional capacity among men in hospitalized cohorts.

BACKGROUND

The first wave of the COVID-19 pandemic in the UK in 2020 led to significant morbidity, hospitalization, and death, particularly amongst elderly men. Recent meta-analyses confirmed that SARS-CoV-2 infection led to reduced testosterone and increased LH, suggestive of testicular Leydig cell involvement.

METHODS

The unique Leydig cell biomarker insulin-like peptide 3 (INSL3) was measured in two cohorts of hospitalized men in Nottingham and London with moderate to severe COVID-19 symptoms.

RESULTS

For Nottingham men, circulating INSL3 was reduced at entry (0.36  0.34 ng/ml; n = 143), indicative of primary hypogonadism, but appeared to recover to normal values after treatment. For the less severely affected London men, INSL3 at entry was within the normal range (0.89 + 0.30 ng/ml; n = 43), though sequential blood sampling suggested a small decline thereafter, which recovered with treatment.

CONCLUSION

In this first study of the biomarker INSL3 in hospitalized men with COVID-19, the results identify a Leydig cell deficiency and consequent hypogonadism as integral to the symptoms of the illness, which was most marked in severely ill patients. In most cases, Leydig cells appeared to recover with treatment. Whether Leydig cells are directly affected by SARS-CoV-2 virus or indirectly via systemic inflammation is unclear, though both are likely.