Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
Toscano-Guerra, Emily (Hospital Universitari Vall d'Hebron)
Martínez Gallo, Mónica (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Arrese-Muñoz, Iria (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Giné Vilalta, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Díaz-Troyano, Noelia (Hospital Universitari Vall d'Hebron)
Gabriel-Medina, Pablo (Hospital Universitari Vall d'Hebron)
Riveiro Barciela, Mar (Hospital Universitari Vall d'Hebron)
Labrador Horrillo, Moises (Hospital Universitari Vall d'Hebron)
Martínez-Valle, Fernando (Hospital Universitari Vall d'Hebron)
Montalvá, Adrián Sánchez (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernández-González, Manuel (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Borrell, Ricardo Pujol (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Rodríguez Frías, Francisco (Hospital Universitari Vall d'Hebron)
Ferrer Costa, Roser (Hospital Universitari Vall d'Hebron)
Thomson, Timothy M. (Plataforma Temática Interdisciplinar Salud Global (Madrid))
Paciucci, Rosanna (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Data:	2022
Resum:	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. 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. 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. 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. The online version contains supplementary material available at 10. 1186/s12916-022-02345-w.
Ajuts:	Agencia Estatal de Investigación RTI2018-096055-B-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2020PANDE00048 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR 1411 GRC Instituto de Salud Carlos III PI18/00346 Instituto de Salud Carlos III COVID-19_00416
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	COVID-19 ; Survival ; Longitudinal ; Testosterone ; Immune phenotype
Publicat a:	BMC Medicine, Vol. 20 (march 2022) , ISSN 1741-7015

DOI: 10.1186/s12916-022-02345-w
PMID: 35351135

18 p, 6.4 MB

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