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1.
BMC Med ; 20(1): 129, 2022 03 29.
Article in English | MEDLINE | ID: covidwho-1770538

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.


Subject(s)
COVID-19 , Androgens , Female , Humans , Luteinizing Hormone/metabolism , Male , SARS-CoV-2 , Testosterone
2.
Horm Metab Res ; 54(3): 153-161, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1740511

ABSTRACT

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.


Subject(s)
Adrenocorticotropic Hormone/blood , COVID-19/immunology , Hypothalamus/immunology , Pituitary Gland/immunology , Adult , Autoantibodies/blood , Autoimmunity , COVID-19/blood , COVID-19/metabolism , COVID-19/virology , Case-Control Studies , Female , Humans , Hydrocortisone/blood , Hypothalamus/metabolism , Insulin-Like Growth Factor I/metabolism , Male , Middle Aged , Pituitary Gland/metabolism , Prolactin/blood , Prospective Studies , SARS-CoV-2/physiology , Testosterone/blood
3.
F S Sci ; 3(1): 29-34, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1671309

ABSTRACT

OBJECTIVE: To confirm if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in semen of men with acute coronavirus disease 2019 and if their male hormone profile (testosterone, follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin, and free androgen index) is adversely affected during the acute phase of infection and any relation to the ACE2 and/or TMPRSS2 expression in human semen. DESIGN: Clinical study. SETTING: National University Hospital, Singapore. PATIENTS: Asian men aged 21-55 years who were admitted to National University Hospital, Singapore, with a laboratory-confirmed diagnosis of SARS-CoV-2 infection via nasopharyngeal swab in the acute phase of the infection, within 2-14 days of the development of symptoms or contact history, were recruited for the study. INTERVENTIONS: Blood was collected in the morning to assess the male hormone profile. Human semen were obtained by masturbation and sent to the molecular diagnostic laboratories to detect the presence of SARS-CoV-2 RNA and assess the ACE2 and TMPRSS2 expression. MAIN OUTCOME MEASURES: Male hormone profile level and expression of SARS-CoV-2 RNA, ACE2, and TMPRSS2 in human semen. RESULTS: A total of 63 men of Asian ethnicities agreed to participate in the study. Subsequently, 65% of recruited men had completely normal levels of male hormone profile. Moreover, 27% were noted to have higher luteinizing hormone levels between 6.6 and 16.1 IU/L (normal range, 0.8-6.1 IU/L), and 10% had higher follicle-stimulating hormone levels between 13.6 and 41.6 IU/L (normal range, 1.5-12.4 IU/L); all had normal testosterone levels. No SARS-CoV-2 RNAs were detected in all human semen. The ACE2 and TMPRSS2 expression was undetectable in 26 samples, whereas 23 samples only had a detectable TMPRSS2 expression and 4 only had an ACE2 expression. The remaining 3 expressed both ACE2 and TMPRSS2. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 could not be found in the semen of a cohort of young to middle-aged Asian men with mild acute SARS-CoV-2 infection. However, there was a detectable expression of ACE2 and TMPRSS2 in semen, although not causal, and it may be correlated to changes in male hormone profiles and male age.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/genetics , Female , Follicle Stimulating Hormone , Humans , Luteinizing Hormone , Male , Middle Aged , RNA, Viral , Seeds , Serine Endopeptidases/genetics , Testosterone
4.
J Endocrinol Invest ; 45(5): 1065-1069, 2022 May.
Article in English | MEDLINE | ID: covidwho-1641053

ABSTRACT

PURPOSE: COVID-19 has worse clinical outcomes in males compared with females and testosterone may determine gender differences. Hypogonadism and supernumerary X chromosome may have a role in the SARS-CoV-2 infection in Klinefelter syndrome (KS). Aim of the study was evaluating COVID-19 frequency and severity in KS. METHODS: Participants were invited to complete a retrospective self-administered questionnaire containing multiple choice and open-ended answers. RESULTS: COVID-19 was detected in 10% of the evaluated KS subjects; none was hospitalized. 44.4% of COVID-19 patients had one cohabitant-infected versus 3% of non-infected (p < 0.01). Testosterone levels in infected patients were lower compared to those of non-infected subjects (3.1 ± 1.2 ng/ml vs. 5.2 ± 2 ng/ml, p < 0.05). CONCLUSIONS: The frequency of SARS-CoV-2 infection among KS subjects was 10%. All infected patients showed mild symptoms. The presence of one affected cohabitant significantly associated with SARS-CoV-2 infection. An association between SARS-CoV-2 and hypogonadism was confirmed.


Subject(s)
COVID-19 , Hypogonadism , Klinefelter Syndrome , COVID-19/complications , Female , Humans , Hypogonadism/complications , Hypogonadism/diagnosis , Hypogonadism/epidemiology , Klinefelter Syndrome/complications , Klinefelter Syndrome/diagnosis , Klinefelter Syndrome/genetics , Male , Retrospective Studies , SARS-CoV-2 , Testosterone
5.
Int J Mol Sci ; 23(2)2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1625531

ABSTRACT

The health scourge imposed on humanity by the COVID-19 pandemic seems not to recede. This fact warrants refined and novel ideas analyzing different aspects of the illness. One such aspect is related to the observation that most COVID-19 casualties were older males, a tendency also noticed in the epidemics of SARS-CoV in 2003 and the Middle East respiratory syndrome in 2012. This gender-related difference in the COVID-19 death toll might be directly involved with testosterone (TEST) and its plasmatic concentration in men. TEST has been demonstrated to provide men with anti-inflammatory and immunological advantages. As the plasmatic concentration of this androgen decreases with age, the health benefit it confers also diminishes. Low plasmatic levels of TEST can be determinant in the infection's outcome and might be related to a dysfunctional cell Ca2+ homeostasis. Not only does TEST modulate the activity of diverse proteins that regulate cellular calcium concentrations, but these proteins have also been proven to be necessary for the replication of many viruses. Therefore, we discuss herein how TEST regulates different Ca2+-handling proteins in healthy tissues and propose how low TEST concentrations might facilitate the replication of the SARS-CoV-2 virus through the lack of modulation of the mechanisms that regulate intracellular Ca2+ concentrations.


Subject(s)
COVID-19/metabolism , COVID-19/mortality , Testosterone/metabolism , Age Factors , Aged , Aging/metabolism , Animals , COVID-19/etiology , Calcium Signaling , Humans , Inflammation/metabolism , Male , Morbidity
6.
J Am Heart Assoc ; 11(1): e023371, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1622137

ABSTRACT

Background Systemic inflammation and male hypogonadism are 2 increasingly recognized "nonconventional" risk factors for long-QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate-corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc. Methods and Results We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10 years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C-reactive protein and interleukin-6 levels. Reduction of testosterone levels, which also inversely correlated with 17-ß estradiol over time, significantly contributed to inflammation-induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C-reactive protein, testosterone, and 17-ß estradiol levels; in these patients, increased C-reactive protein and reduced testosterone were associated with a worse short-term outcome of the arrhythmia. Conclusions During systemic inflammatory activation, interleukin-6 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen-to-estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long-QT syndrome/TdP risk in men.


Subject(s)
Hypogonadism , Long QT Syndrome , Torsades de Pointes , C-Reactive Protein , DNA-Binding Proteins , Electrocardiography , Estradiol , Gonadal Steroid Hormones , Heart Rate , Humans , Hypogonadism/complications , Hypogonadism/diagnosis , Inflammation/complications , Interleukin-6 , Long QT Syndrome/chemically induced , Male , Risk Factors , Testosterone , Torsades de Pointes/chemically induced , Torsades de Pointes/diagnosis
7.
Arch Ital Urol Androl ; 93(4): 460-464, 2021 Dec 21.
Article in English | MEDLINE | ID: covidwho-1594656

ABSTRACT

OBJECTIVE: We aimed to investigate the relationship between COVID-19 and Erectile Dysfunction (ED) and the effect of serum testosterone level on the disease prognosis. METHODS: Between April-December 2020, 70 patients who were admitted with a complaint of ED after having COVID-19 and whose serum testosterone level was checked for varicocele, premature ejaculation, and infertility reasons before COVID-19. The patients filled the International Index of Erectile Function (IIEF-5) and their testosterone level was checked. The questionnaire was arranged to assess the first month before COVID-19 and after COVID-19. Testosterone levels of the patients before and after COVID-19 were compared. The relationship between testosterone levels and hospitalization in the intensive care was evaluated. RESULTS: It was revealed that testosterone levels and IIEF-5 scores after COVID-19 in all patients were statisticaly and significantly different compared to the period before COVID-19 (p < 0.05). Testosterone levels of patients in need of intensive care were significantly higher than those without any need of intensive care (p < 0.05). CONCLUSIONS: Our study has presented that COVID-19 may cause ED and high testosterone levels increase the rate of hospitalization in the intensive care by intensifying the disease.


Subject(s)
COVID-19 , Erectile Dysfunction , Premature Ejaculation , Erectile Dysfunction/epidemiology , Erectile Dysfunction/etiology , Humans , Male , SARS-CoV-2 , Testosterone
8.
Clin Chim Acta ; 524: 132-138, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1576025

ABSTRACT

BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet. METHODS: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients. RESULTS: Testosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 âˆ¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 âˆ¼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone. CONCLUSIONS: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.


Subject(s)
COVID-19 , Testosterone , Female , Gene Expression Profiling , Humans , Immunity , Leukocytes, Mononuclear , Male , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes
9.
Eur Urol ; 81(3): 285-293, 2022 03.
Article in English | MEDLINE | ID: covidwho-1568696

ABSTRACT

BACKGROUND: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. OBJECTIVE: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. DESIGNS, SETTINGS, AND PARTICIPANTS: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2-positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. INTERVENTION: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. OUTCOME MEASUREMENTS: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. RESULTS AND LIMITATIONS: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20-0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52-4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. CONCLUSIONS: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. PATIENT SUMMARY: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.


Subject(s)
Androgen Antagonists/therapeutic use , Anilides/therapeutic use , Benzamides/therapeutic use , COVID-19/drug therapy , Nitriles/therapeutic use , Phenylthiohydantoin/therapeutic use , SARS-CoV-2/isolation & purification , Tosyl Compounds/therapeutic use , Aged , Aged, 80 and over , Androgens/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Sweden/epidemiology , Testosterone , Treatment Outcome
10.
Biol Sex Differ ; 12(1): 63, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528694

ABSTRACT

BACKGROUND: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. METHODS: Plasma levels of sex hormones (testosterone and 17ß-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. RESULTS: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. CONCLUSIONS: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.


Subject(s)
Biomarkers/blood , COVID-19/complications , Hospitalization , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/diagnosis , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Sex Characteristics , Adult , Angiotensin-Converting Enzyme 2/blood , Angiotensins/blood , COVID-19/blood , Estradiol/blood , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/blood , Respiratory Insufficiency/blood , SARS-CoV-2 , Testosterone/blood
11.
J Sex Marital Ther ; 48(4): 415-426, 2022.
Article in English | MEDLINE | ID: covidwho-1528058

ABSTRACT

Based on the possible effects of androgens on the course of COVID-19, it can be posited that Gender-Affirming Hormone Therapy (GAHT) may affect the course of the disease in people with GD. We aimed to investigate the relationship between GAHT and contracting COVID-19, as well as the severity of the disease in individuals with Gender Dysphoria (GD). The single center, cross-sectional, web-based survey was completed by people with GD who received GAHT. The questionnaire contained three parts: a sociodemographic data form; a GAHT data form; a COVID-19-related data form. Of the 238 participants, 179 were individuals with female-to-male (FtM) and 59 male-to-female (MtF) GD. We detected that the risk of contracting COVID-19 increased 3.46 times in people with FtM GD, who had received testosterone therapy, in comparison to people with MtF GD, who received estrogen and anti-androgen therapy. Additionally, people with FtM GD who contracted COVID-19 had received longer testosterone therapy when compared to those who did not contract COVID-19. Our findings indicate that individuals with FtM GD who receive testosterone treatment within the scope of GAHT are at higher risk of contracting COVID-19 and that the clinicians who follow-up on GAHT should be more careful about this issue.


Subject(s)
COVID-19 , Gender Dysphoria , Transgender Persons , COVID-19/drug therapy , COVID-19/epidemiology , Cross-Sectional Studies , Female , Gender Dysphoria/therapy , Humans , Male , Testosterone/therapeutic use
12.
J Endocrinol Invest ; 45(4): 753-762, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1520532

ABSTRACT

PURPOSE: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19). METHODS: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality. RESULTS: Subjects low T values (< 8 nmol/L; 176 cases) were significantly older (P = 0.001) and had higher serum interleukin-6 (P = 0.001), C-reactive protein (P < 0.001), lactate dehydrogenase (P < 0.001), ferritin (P = 0.012), lower P/F ratio (P = 0.001), increased prevalence of low T3 syndrome (P = 0.041), acute respiratory insufficiency (P < 0.001), more frequently need of ventilation (P < 0.001) and higher mortality rate (P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79-0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69-0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation. CONCLUSION: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.


Subject(s)
COVID-19/complications , Respiratory Insufficiency/etiology , Testosterone/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , Hospitalization , Humans , Italy/epidemiology , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/mortality , Survival Rate
13.
Minerva Endocrinol (Torino) ; 47(1): 127, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1506477
14.
J Endocrinol Invest ; 45(3): 639-648, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1499558

ABSTRACT

PURPOSE: Objective of this study was to assess the association between testosterone (T) levels and biochemical markers in a cohort of female patients admitted for SARS-CoV-2 infection in a respiratory intensive care unit (RICU). METHODS: A consecutive series of 17 women affected by SARSCoV-2 pneumonia and recovered in the RICU of the Hospital of Mantua were analyzed. Biochemical inflammatory markers as well as total testosterone (TT), calculated free T (cFT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were determined. RESULTS: TT and cFT were significantly and positively associated with PCT, CRP, and fibrinogen as well as with a worse hospital course. We did not observe any significant association between TT and cFT with LH; conversely, both TT and cFT showed a positive correlation with cortisol. By LOWESS analysis, a linear relationship could be assumed for CRP and fibrinogen, while a threshold effect was apparent in the relationship between TT and procalcitonin, LDH and ferritin. When the TT threshold value of 1 nmol/L was used, significant associations between TT and PCT, LDH or ferritin were observed for values above this value. For LDH and ferritin, this was confirmed also in an age-adjusted model. Similar results were found for the association of cFT with the inflammatory markers with a threshold effect towards LDH and ferritin with increased LDH and ferritin levels for values above cFT 5 pmol/L. Cortisol is associated with serum inflammatory markers with similar trends observed for TT; conversely, the relationship between LH and inflammatory markers had different trends. CONCLUSION: Opposite to men, in women with SARS-CoV-2 pneumonia, higher TT and cFT are associated with a stronger inflammatory status, probably related to adrenal cortex hyperactivity.


Subject(s)
Biomarkers/blood , COVID-19/blood , Inflammation/blood , SARS-CoV-2 , Testosterone/blood , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Intensive Care Units , Luteinizing Hormone/blood , Middle Aged , Severity of Illness Index , Sex Hormone-Binding Globulin/analysis
15.
Eur Rev Med Pharmacol Sci ; 25(19): 5889-5903, 2021 10.
Article in English | MEDLINE | ID: covidwho-1478931

ABSTRACT

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.


Subject(s)
COVID-19/blood , COVID-19/mortality , Estradiol/blood , Inflammation/blood , Inflammation/etiology , Testosterone/blood , Vitamin D/analogs & derivatives , Adult , Aged , Aged, 80 and over , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Hospitalization , Humans , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Procalcitonin/blood , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis , Vitamin D/blood
16.
Medicine (Baltimore) ; 100(34): e27072, 2021 Aug 27.
Article in English | MEDLINE | ID: covidwho-1443147

ABSTRACT

ABSTRACT: In patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.We selected patients from the Amsterdam University Medical Centers COVID-19 Biobank, in which patients admitted to hospital in March and April 2020, with reverse transcription-polymerase chain reaction proven severe acute respiratory syndrome-coronavirus-2 infection, were prospectively included. Specifically, we included postmenopausal women (>55 years) and age-matched men, with a mortality of 50% in each group. Residual plasma samples were used to measure testosterone, estradiol, sex hormone binding globulin (SHBG), and albumin. We investigated the association of the levels of these hormones with mortality in men and women.We included 16 women and 24 men in March and April 2020 of whom 7 (44%) and 13 (54%), respectively, died. Median age was 69 years (interquartile range [IQR] 64-75). In men, both total and free testosterone was significantly lower in deceased patients (median testosterone 0.8 nmol/L [IQR 0.4-1.9] in deceased patients vs 3.2 nmol/L [IQR 2.1-7.5] in survivors; P < .001, and median free testosterone 33.2 pmol/L [IQR 15.3-52.2] in deceased patients vs 90.3 pmol/L [IQR 49.1-209.7] in survivors; P = .002). SHBG levels were significantly lower in both men and women who died (18.5 nmol/L [IQR 11.3-24.3] in deceased patients vs 34.0 nmol/L [IQR 25.0-48.0] in survivors; P < .001). No difference in estradiol levels was found between deceased and surviving patients.Low SHBG levels were associated with mortality rate in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men. The role of testosterone and SHBG and potential of hormone replacement therapy needs further exploration in COVID-19.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Gonadal Steroid Hormones/analysis , Aged , Albumins/analysis , COVID-19/mortality , Comorbidity , Estradiol/blood , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Sex Hormone-Binding Globulin/analysis , Testosterone/blood
17.
Front Cell Infect Microbiol ; 11: 666987, 2021.
Article in English | MEDLINE | ID: covidwho-1441099

ABSTRACT

COVID-19 is a pandemic disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), which leads to pulmonary manifestations like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In addition, COVID-19 may cause extra-pulmonary manifestation such as testicular injury. Both high and low levels of testosterone could affect the severity of COVID-19. Herein, there is substantial controversy regarding the potential role of testosterone in SARS-CoV-2 infection and COVID-19 severity. Therefore, the present study aimed to review and elucidate the assorted view of preponderance regarding the beneficial and harmful effects of testosterone in COVID-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done. All published articles related to the role of testosterone and COVID-19 were included in this mini-review. The beneficial effects of testosterone in COVID-19 are through inhibition of pro-inflammatory cytokines, augmentation of anti-inflammatory cytokines, modulation of the immune response, attenuation of oxidative stress, and endothelial dysfunction. However, its harmful effects in COVID-19 are due to augmentation of transmembrane protease serine 2 (TMPRSS2), which is essential for cleaving and activating SARS-CoV-2 spike protein during acute SARS-CoV-2 infection. Most published studies illustrated that low testosterone levels are linked to COVID-19 severity. A low testosterone level in COVID-19 is mainly due to testicular injury, the primary source of testosterone.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Testosterone
18.
Minerva Endocrinol (Torino) ; 47(1): 111-116, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1431239

ABSTRACT

BACKGROUND: Low testosterone (mainly total testosterone [TTe]) has been noted in patients with COVID-19. Calculated free testosterone (FTe) and bioavailable testosterone (BavTe) may reflect more accurately this hormone's levels. In this study, we sought to assess TTe, FTe as well as BavTe in male patients with COVID-19. METHODS: Sera were collected upon admission from 65 men (10 in the intensive care units [ICU] and 55 in the wards) with polymerase chain reaction - proven COVID-19. A group of age-matched COVID-19-negative men (N.=29) hospitalized in general medical wards served as controls. Age, Body Mass Index (BMI) and 28-day mortality were noted. Measurements included TTe, sex-hormone binding globulin, albumin (the latter two for calculating FTe and BavTe) and laboratory markers of inflammation (white blood cell count [WBC], D-Dimers [D-D], lactate dehydrogenase [LDH], ferritin [Fer] and C-reactive protein [CRP]). RESULTS: Profoundly low TTe, FTe and BavTe were noted in most patients, and were associated with disease severity/outcome (being the lowest in COVID-19 patients in the ICU and overall being lower in non-survivors; analysis of covariance P<0.05). Pearson's correlations for logTe, logFTe or logBavTe versus WBC, D-D, LDH, Ferr or CRP were negative, ranging from -0.403 to -0.293 (P=0.009 to 0.014). CONCLUSIONS: TTe, FTe and BavTe are prone to be low in patients with COVID-19, are negatively associated with disease severity and may be considered to have prognostic value.


Subject(s)
COVID-19 , Testosterone , Biomarkers , C-Reactive Protein , Female , Humans , Leukocyte Count , Male
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