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Association Between Sex Hormones Levels and Clinical Outcomes in Patients With COVID-19 Admitted to Hospital: An Observational, Retrospective, Cohort Study

33 Pages Posted: 10 Nov 2021

See all articles by anna beltrame

anna beltrame

Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) - Department of Infectious-Tropical Diseases and Microbiology

Pedro Salguero Garcia

Prince Felipe Research Center - Genomics of Gene Expression Laboratory

Emanuela Rossi

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging

Ana Conesa

University of Florida - Genetics Institute

Lucia Moro

Sacro Cuore Don Calabria Hospital - Department of Infectious

Laura Rachele Bettini

MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale - Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet

Eleonora Rizzi

Sacro Cuore Don Calabria Hospital - Department of Infectious

Mariella D'Angio'

MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale - Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet

Michela Deiana

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology

Chiara Piubelli

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology

Paola Rebora

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging

Silvia Duranti

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging

Paolo Bonfanti

Milano-Bicocca University - School of Medicine and Surgery

Ilaria Capua

University of Florida

Sonia Tarazona Campos

Prince Felipe Research Center - Genomics of Gene Expression Laboratory

Maria Grazia Valsecchi

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging

More...

Abstract

Background: Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age.

Methods: This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed.

Findings: The median age was 73·5 years [IQR 61, 82]; 55·8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3·6 vs. 5·3 nmol/L, p =0·0378 and 3·7 vs. 8·5 nmol/L, p =0·0011, respectively). Deceased males had lower testosterone (2·4 vs. 4·8 nmol/L, p =0·0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0·0006). Testosterone was negatively associated with ARDS (OR 0·849 [95% CI 0·734, 0·982]), severe COVID-19 (OR 0·691 [95% CI 0·546, 0·874]), and in-hospital mortality (OR 0·742 [95% CI 0·566, 0·972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1·051 [95% CI 1·018, 1.084]), confirmed in both sex models. 

Interpretation: In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes.

Funding Information: The research was funded by Italian Ministry of Health “Fondi Ricerca Corrente, Project L1P5” for IRCCS Sacro Cuore Don Calabria Hospital.

Declaration of Interests: We declare there is no conflict of interest.

Ethics Approval Statement: Ethical approval for data collection was obtained in accordance with local regulations at each participating site. The study protocol received ethical approval and consent from the competent Ethics Committee (Comitato Etico per la sperimentazione Clinica delle Province di Verona e Rovigo) on September 1st, 2020 (protocol #46555).

Keywords: Covid-19, SARS-CoV-2, sex hormones, testosterone, estradiol, progesterone, dehydroepiandrosterone, sex, outcome, observational.

Suggested Citation

beltrame, anna and Salguero Garcia, Pedro and Rossi, Emanuela and Conesa, Ana and Moro, Lucia and Bettini, Laura Rachele and Rizzi, Eleonora and D'Angio', Mariella and Deiana, Michela and Piubelli, Chiara and Rebora, Paola and Duranti, Silvia and Bonfanti, Paolo and Capua, Ilaria and Tarazona Campos, Sonia and Valsecchi, Maria Grazia, Association Between Sex Hormones Levels and Clinical Outcomes in Patients With COVID-19 Admitted to Hospital: An Observational, Retrospective, Cohort Study. Available at SSRN: https://ssrn.com/abstract=3960674 or http://dx.doi.org/10.2139/ssrn.3960674

Anna Beltrame (Contact Author)

Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) - Department of Infectious-Tropical Diseases and Microbiology ( email )

Negrar
Italy

Pedro Salguero Garcia

Prince Felipe Research Center - Genomics of Gene Expression Laboratory ( email )

46012 Valencia
Spain

Emanuela Rossi

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging ( email )

Italy

Ana Conesa

University of Florida - Genetics Institute ( email )

Gainsville, FL 32610-3610
United States

Lucia Moro

Sacro Cuore Don Calabria Hospital - Department of Infectious ( email )

37024 Negrar di Valpolicella
Verona
Italy

Laura Rachele Bettini

MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale - Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet ( email )

20052 Monza
San Gerardo
Italy

Eleonora Rizzi

Sacro Cuore Don Calabria Hospital - Department of Infectious ( email )

37024 Negrar di Valpolicella
Verona
Italy

Mariella D'Angio'

MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale - Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet ( email )

20052 Monza
San Gerardo
Italy

Michela Deiana

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology ( email )

Verona
Italy

Chiara Piubelli

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology ( email )

Verona
Italy

Paola Rebora

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging ( email )

Italy

Silvia Duranti

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging ( email )

Italy

Paolo Bonfanti

Milano-Bicocca University - School of Medicine and Surgery ( email )

20126 Milano
Italy

Ilaria Capua

University of Florida ( email )

PO Box 117165, 201 Stuzin Hall
Gainesville, FL 32610-0496
United States

Sonia Tarazona Campos

Prince Felipe Research Center - Genomics of Gene Expression Laboratory ( email )

46012 Valencia
Spain

Maria Grazia Valsecchi

Milano-Bicocca University - Bicocca Center of Bioinformatics, Biostatistics and Bioimaging ( email )

Italy

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