COVID-19 and Leydig Cell Functional Capacity: INSL3 as a Biomarker of Testicular Peptide Deficiency
Anand-Ivell R, Yang X, Tarr AW, Irving WI, Clark DJ, Staines HM, Augustin Y, Krishna S, Ivell R
Summary
This study measured insulin-like peptide 3 (INSL3), a unique Leydig cell biomarker, in hospitalized men with COVID-19. Severely ill patients showed significantly reduced INSL3 (0.36 vs normal ~0.89 ng/ml), indicating primary hypogonadism. Most patients recovered Leydig cell function with treatment, suggesting the effect was largely reversible.
Clinical Significance
First study to use INSL3 — a peptide biomarker — to characterize testicular dysfunction in COVID-19. The finding that Leydig cell peptide production is impaired during severe infection has implications for male reproductive health assessment post-COVID and validates INSL3 as a clinical biomarker.
Key Findings
- Severe COVID (Nottingham, n=143): INSL3 reduced to 0.36 ng/ml at admission
- Moderate COVID (London, n=43): INSL3 within normal range at admission (0.89 ng/ml)
- Recovery: Leydig cell function recovered in most patients with treatment
- Mechanism: Both direct viral effect and systemic inflammation likely contribute
Clinical Implications
INSL3 could serve as a more specific biomarker for Leydig cell function than testosterone alone. Post-COVID male reproductive assessments should consider INSL3 measurement. The reversibility finding is reassuring but warrants monitoring in severe cases.
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