Inverse correlation between central hypogonadism and circulating IL-10 levels in males with severe COVID-19

ABSTRACT

Introduction & Objectives: After the early and dramatic induction of inflammatory cytokines, IL-6 emerged to be associated with severe outcomes in patients with COVID-19. Likewise, high IL-10 plasma levels have been reported, and central hypogonadism has been recently observed in male patients with severe clinical outcomes (i.e., Intensive Care Unit (ICU) admission or death) of COVID-19. We aimed to investigate the role of IL-10 over the pathophysiology of COVID-19 and its relationship with hypogonadism in males. Materials & Methods: Plasma from 281 voluntary healthy males (HC) and 258 laboratory-confirmed COVID-19 males (i.e., asymptomatic (n=24);symptomatic (n=155);ICU patients (n=48);and, deceased (n=31)) was collected to measure levels of total testosterone (TT), IL-10 and the nonclassical MHC class I HLA-G (HLA-G) molecule - associated to IL-10 and involved in immune escape after viral infection - by specific enzyme-linked immunosorbent assay. Results: An inverse correlation between TT and IL-10 levels was identified, with TT levels progressively decreasing from HC (median (IQR) 10.4 (8.1-13.4) nmol/L) to asymptomatic COVID-19 (3.9 (3.1-5.3) nmol/L), to symptomatic COVID-19 (3.0 (1.8-5.7) nmol/L), ICU (1.0 (0.5-1.8) nml/L) and deceased (0.7 (0.3-2.3) nmol/L) patients, respectively (p<0.0001). Conversely, IL-10 levels progressively decreased from deceased COVID-19 patients (11.3 (4.5-37.7) pg/ml), to ICU (8.0 (2.6-16.7) pg/mL), symptomatic (6.0 (3.0-10.9) pg/mL), asymptomatic COVID-19 patients (6.0 (1.6-6.0) pg/mL), and HC (3.0 (1.3-3.0) pg/mL), respectively (p<0.0001). Similarly, HLA-G levels, progressively increased from HC to COVID-19 patients with most severe clinical outcomes. Conclusions: These data indicate that circulating TT is inversely associated to both IL-10 and HLA-G levels in men with COVID-19, where lower TT and higher IL-10 levels are associated with the most severe clinical outcomes. Further investigations are required to better define whether TT and IL-10 might be early effective biomarkers of clinical severity in males with COVID-19 and to exploit if TT is involved in promoting IL-10 and HLA-G induction.