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Open Access 01-12-2022 | COVID-19 | Research article

Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients

Authors: Emily Toscano-Guerra, Mónica Martínez-Gallo, Iria Arrese-Muñoz, Anna Giné, Noelia Díaz-Troyano, Pablo Gabriel-Medina, Mar Riveiro-Barciela, Moisés Labrador-Horrillo, Fernando Martinez-Valle, Adrián Sánchez Montalvá, Manuel Hernández-González, Ricardo Pujol Borrell, Francisco Rodríguez-Frias, Roser Ferrer, Timothy M. Thomson, Rosanna Paciucci

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

SARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients.

Methods

Biochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome.

Results

We have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes.

Conclusions

Recovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.

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Title: Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
Authors: Emily Toscano-Guerra
Mónica Martínez-Gallo
Iria Arrese-Muñoz
Anna Giné
Noelia Díaz-Troyano
Pablo Gabriel-Medina
Mar Riveiro-Barciela
Moisés Labrador-Horrillo
Fernando Martinez-Valle
Adrián Sánchez Montalvá
Manuel Hernández-González
Ricardo Pujol Borrell
Francisco Rodríguez-Frias
Roser Ferrer
Timothy M. Thomson
Rosanna Paciucci
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: COVID-19
Testosterone
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-022-02345-w

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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