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

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 th...

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Autores principales: Toscano-Guerra, Emily, Gallo, Mónica Martínez, Arrese-Muñoz, Iria, Giné, Anna, Díaz-Troyano, Noelia, Gabriel-Medina, Pablo, Riveiro-Barciela, Mar, Labrador-Horrillo, Moisés, Martinez-Valle, Fernando, Montalvá, Adrián Sánchez, Hernández-González, Manuel, Borrell, Ricardo Pujol, Rodríguez-Frias, Francisco, Ferrer, Roser, Thomson, Timothy M., Paciucci, Rosanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963401/
https://www.ncbi.nlm.nih.gov/pubmed/35351135
http://dx.doi.org/10.1186/s12916-022-02345-w
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author Toscano-Guerra, Emily
Gallo, Mónica Martínez
Arrese-Muñoz, Iria
Giné, Anna
Díaz-Troyano, Noelia
Gabriel-Medina, Pablo
Riveiro-Barciela, Mar
Labrador-Horrillo, Moisés
Martinez-Valle, Fernando
Montalvá, Adrián Sánchez
Hernández-González, Manuel
Borrell, Ricardo Pujol
Rodríguez-Frias, Francisco
Ferrer, Roser
Thomson, Timothy M.
Paciucci, Rosanna
author_facet Toscano-Guerra, Emily
Gallo, Mónica Martínez
Arrese-Muñoz, Iria
Giné, Anna
Díaz-Troyano, Noelia
Gabriel-Medina, Pablo
Riveiro-Barciela, Mar
Labrador-Horrillo, Moisés
Martinez-Valle, Fernando
Montalvá, Adrián Sánchez
Hernández-González, Manuel
Borrell, Ricardo Pujol
Rodríguez-Frias, Francisco
Ferrer, Roser
Thomson, Timothy M.
Paciucci, Rosanna
author_sort Toscano-Guerra, Emily
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02345-w.
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spelling pubmed-89634012022-03-30 Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients Toscano-Guerra, Emily Gallo, Mónica Martínez Arrese-Muñoz, Iria Giné, Anna Díaz-Troyano, Noelia Gabriel-Medina, Pablo Riveiro-Barciela, Mar Labrador-Horrillo, Moisés Martinez-Valle, Fernando Montalvá, Adrián Sánchez Hernández-González, Manuel Borrell, Ricardo Pujol Rodríguez-Frias, Francisco Ferrer, Roser Thomson, Timothy M. Paciucci, Rosanna BMC Med Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02345-w. BioMed Central 2022-03-29 /pmc/articles/PMC8963401/ /pubmed/35351135 http://dx.doi.org/10.1186/s12916-022-02345-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Toscano-Guerra, Emily
Gallo, Mónica Martínez
Arrese-Muñoz, Iria
Giné, Anna
Díaz-Troyano, Noelia
Gabriel-Medina, Pablo
Riveiro-Barciela, Mar
Labrador-Horrillo, Moisés
Martinez-Valle, Fernando
Montalvá, Adrián Sánchez
Hernández-González, Manuel
Borrell, Ricardo Pujol
Rodríguez-Frias, Francisco
Ferrer, Roser
Thomson, Timothy M.
Paciucci, Rosanna
Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
title Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
title_full Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
title_fullStr Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
title_full_unstemmed Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
title_short Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
title_sort recovery of serum testosterone levels is an accurate predictor of survival from covid-19 in male patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963401/
https://www.ncbi.nlm.nih.gov/pubmed/35351135
http://dx.doi.org/10.1186/s12916-022-02345-w
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