Combined plasma levels of IL-10 and testosterone, but not soluble HLA-G5, predict the risk of death in COVID-19 patients.

BACKGROUND: The identification of biomarkers correlated with COVID-19 outcomes is a relevant need for clinical management. SARS-CoV-2 infection is characterized by elevated IL-6, IL-10, and HLA-G and impaired testosterone production. OBJECTIVES: We aimed at defining the combined impact of sex hormones, IL-10, and HLA-G on COVID-19 pathophysiology and their relationship in male patients. MATERIALS AND METHODS: We measured by chemiluminescence immunoassay (CLIA), ECLIA and ELISA circulating total testosterone, 17β-estradiol (E2 ), IL-10, and HLA-G5 as well as SARS-CoV-2 S1/S2 IgG from 292 healthy controls and 111 COVID-19 patients with different disease severity at hospital admission, and in 53 COVID-19 patients at 7-month follow-up. RESULTS AND DISCUSSION: We found significantly higher levels of IL-10, HLA-G5, and E2 in COVID-19 patients compared to healthy controls and an inverse correlation between IL-10 and testosterone, with IL-10 progressively increasing and testosterone progressively decreasing with disease severity. This correlation was lost at 7-month follow-up. The risk of death in COVID-19 patients with low testosterone increased in the presence of high IL-10. A negative correlation between SARS-CoV-2 IgG and HLA-G5 or IL-10 at hospitalization was observed. At 7-month follow-up, IL-10 and testosterone normalized and HLA-G5 decreased. CONCLUSION: Our findings indicate that combined evaluation of IL-10 and testosterone predicts the risk of death in men with COVID-19 and support the hypothesis that IL-10 fails to suppress excessive inflammation by promoting viral spreading. This article is protected by copyright. All rights reserved.