scholarly journals Sex Hormones and Hormone Therapy during COVID-19 Pandemic: Implications for Patients with Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2325
Author(s):  
Carlo Cattrini ◽  
Melissa Bersanelli ◽  
Maria Maddalena Latocca ◽  
Benedetta Conte ◽  
Giacomo Vallome ◽  
...  
Keyword(s):  
Hormone Therapy ◽  
Sex Hormones ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Host Cells ◽  
Testosterone Levels ◽  
Increased Risk ◽  
Hormonal Therapies ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

The novel coronavirus disease 2019 (COVID-19) shows a wide spectrum of clinical presentations, severity, and fatality rates. The reason older patients and males show increased risk of severe disease and death remains uncertain. Sex hormones, such as estradiol, progesterone, and testosterone, might be implicated in the age-dependent and sex-specific severity of COVID-19. High testosterone levels could upregulate transmembrane serine protease 2 (TMPRSS2), facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells via angiotensin-converting enzyme 2 (ACE2). Data from patients with prostate cancer treated with androgen-deprivation therapy seem to confirm this hypothesis. Clinical studies on TMPRSS2 inhibitors, such as camostat, nafamostat, and bromhexine, are ongoing. Antiandrogens, such as bicalutamide and enzalutamide, are also under investigation. Conversely, other studies suggest that the immune modulating properties of androgens could protect from the unfavorable cytokine storm, and that low testosterone levels might be associated with a worse prognosis in patients with COVID-19. Some evidence also supports the notion that estrogens and progesterone might exert a protective effect on females, through direct antiviral activity or immune-mediated mechanisms, thus explaining the higher COVID-19 severity in post-menopausal women. In this perspective, we discuss the available evidence on sex hormones and hormone therapy in patients infected with SARS-CoV-2, and we highlight the possible implications for cancer patients, who can receive hormonal therapies during their treatment plans.

scholarly journals SARS-CoV-2 Is Not Detected in the Cerebrospinal Fluid of Encephalopathic COVID-19 Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Dimitris G. Placantonakis ◽  
Maria Aguero-Rosenfeld ◽  
Abdallah Flaifel ◽  
John Colavito ◽  
Kenneth Inglima ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Viral Entry ◽  
Cell Types ◽  
Host Cells ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Neurologic Sequelae ◽  
Show Evidence ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.

scholarly journals Endogenous Testosterone Levels and the Risk of Incident Cardiovascular Events in Elderly Men: The MrOS Prospective Study

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Tinh-Hai Collet ◽  
Susan K Ewing ◽  
Kristine E Ensrud ◽  
Gail A Laughlin ◽  
Andrew R Hoffman ◽  
...  
Keyword(s):  
Prospective Study ◽  
Sex Hormones ◽  
Community Dwelling ◽  
Sex Hormone Binding Globulin ◽  
Total Testosterone ◽  
Continuous Variables ◽  
Elderly Men ◽  
Sleep Study ◽  
Testosterone Levels ◽  
Increased Risk

Abstract Context Observational studies show discordant links between endogenous testosterone levels and cardiovascular diseases (CVD). Objective We assessed whether sex hormones and sex hormone–binding globulin (SHBG) are associated with CVD in community-dwelling elderly men. Design, Setting and Participants Prospective study of incident CVD among 552 men ≥ 65 years in the MrOS Sleep Study without prevalent CVD and no testosterone therapy at baseline. Outcomes Fasting serum levels of total testosterone and estradiol were measured using liquid chromatography-mass spectrometry, and SHBG by chemiluminescent substrate. The association of sex hormones and SHBG with incident coronary heart disease (CHD), cerebrovascular (stroke and transient ischemic attack) and peripheral arterial disease (PAD) events were assessed by quartile and per SD increase in proportional hazards models. Results After 7.4 years, 137 men (24.8%) had at least 1 CVD event: 90 CHD, 45 cerebrovascular and 26 PAD. The risk of incident CVD events was not associated with quartiles of baseline sex hormones or SHBG (all P ≥ 0.16). For +1 SD in total testosterone, the multivariate-adjusted hazard ratio was 1.04 (95% CI, 0.80-1.34) for CHD, 0.86 (0.60-1.25) for cerebrovascular, and 0.81 (0.52-1.26) for PAD events. When analyzed as continuous variables or comparing highest to low quartile, levels of bioavailable testosterone, total estradiol, testosterone/estradiol ratio and SHBG were not associated with CVD events. Conclusions In community-dwelling elderly men, endogenous levels of testosterone, estradiol, and SHBG were not associated with increased risk of CHD, cerebrovascular, or PAD events. These results are limited by the small number of events and should be explored in future studies.

scholarly journals Obesity and COVID-19: what makes obese host so vulnerable?

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sameer Mohammad ◽  
Rafia Aziz ◽  
Saeed Al Mahri ◽  
Shuja Shafi Malik ◽  
Esraa Haji ◽  
...  
Keyword(s):  
Severe Disease ◽  
Mortality Rates ◽  
Published Data ◽  
Disease Pathogenesis ◽  
Obesity And Overweight ◽  
Increased Risk ◽  
Severity Of The Disease ◽  
Novel Coronavirus ◽  
Significant Mortality

AbstractThe disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome.

scholarly journals Post-COVID-19 Pulmonary Fibrosis: Novel Sequelae of the Current Pandemic

2021 ◽  
Vol 10 (11) ◽  
pp. 2452
Author(s):  
Shiva Rattan Ambardar ◽  
Stephanie L. Hightower ◽  
Nikhil A. Huprikar ◽  
Kevin K. Chung ◽  
Anju Singhal ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Severe Disease ◽  
Pulmonary Complications ◽  
Patient Specific ◽  
Pulmonary Vascular Disease ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Novel Coronavirus

Since the initial identification of the novel coronavirus SARS-CoV-2 in December 2019, the COVID-19 pandemic has become a leading cause of morbidity and mortality worldwide. As effective vaccines and treatments begin to emerge, it will become increasingly important to identify and proactively manage the long-term respiratory complications of severe disease. The patterns of imaging abnormalities coupled with data from prior coronavirus outbreaks suggest that patients with severe COVID-19 pneumonia are likely at an increased risk of progression to interstitial lung disease (ILD) and chronic pulmonary vascular disease. In this paper, we briefly review the definition, classification, and underlying pathophysiology of interstitial lung disease (ILD). We then review the current literature on the proposed mechanisms of lung injury in severe COVID-19 infection, and outline potential viral- and immune-mediated processes implicated in the development of post-COVID-19 pulmonary fibrosis (PCPF). Finally, we address patient-specific and iatrogenic risk factors that could lead to PCPF and discuss strategies for reducing risk of pulmonary complications/sequelae.

scholarly journals Elevated D-Dimer Levels are Associated with Increased Risk of Mortality in COVID-19: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Siddharth Shah ◽  
Kuldeep Shah ◽  
Siddharth B Patel ◽  
Forum S Patel ◽  
Mohammed Osman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Severe Disease ◽  
Case Fatality ◽  
Inclusion Criteria ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Novel Coronavirus ◽  
D Dimer

AbstractIntroductionThe 2019 novel Coronavirus (2019-nCoV), now declared a pandemic has an overall case fatality of 2–3% but it is as high as 50% in critically ill patients. D-dimer is an important prognostic tool, often elevated in patients with severe COVID-19 infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of D-dimer in COVID-19 infected patients.MethodsWe searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission D-dimer levels in COVID-19 patients and its effect on mortality.Results18 studies (16 retrospective and 2 prospective) with a total of 3,682 patients met the inclusion criteria. The pooled mean difference (MD) suggested significantly elevated D-dimer levels in patients who died versus those survived (MD 6.13 mg/L, 95% CI 4.16 − 8.11, p <0.001). Similarly, the pooled mean D-dimer levels were significantly elevated in patients with severe COVID-19 infection (MD 0.54 mg/L, 95% CI 0.28 − 0.8, p< 0.001). In addition, the risk of mortality was four-fold higher in patients with positive D-dimer vs negative D-dimer (RR 4.11, 95% CI 2.48 − 6.84, p< 0.001) and the risk of developing the severe disease was two-fold higher in patients with positive D-dimer levels vs negative D-dimer (RR 2.04, 95% CI 1.34 − 3.11, p < 0.001).ConclusionOur meta-analysis demonstrates that patients with COVID-19 presenting with elevated D-dimer levels have an increased risk of severe disease and mortality.

scholarly journals Combinatorial Analysis of Phenotypic and Clinical Risk Factors Associated With Hospitalized COVID-19 Patients

2021 ◽  
Vol 3 ◽  
Author(s):  
Sayoni Das ◽  
Matthew Pearson ◽  
Krystyna Taylor ◽  
Veronique Bouchet ◽  
Gert Lykke Møller ◽  
...  
Keyword(s):  
Risk Factors ◽  
Severe Disease ◽  
Host Cells ◽  
Combinatorial Analysis ◽  
Lipid Signaling ◽  
Phenotypic Data ◽  
Factors Associated ◽  
Increased Risk ◽  
Different Populations ◽  
Disease Signatures

Characterization of the risk factors associated with variability in the clinical outcomes of COVID-19 is important. Our previous study using genomic data identified a potential role of calcium and lipid homeostasis in severe COVID-19. This study aimed to identify similar combinations of features (disease signatures) associated with severe disease in a separate patient population with purely clinical and phenotypic data. The PrecisionLife combinatorial analytics platform was used to analyze features derived from de-identified health records in the UnitedHealth Group COVID-19 Data Suite. The platform identified and analyzed 836 disease signatures in two cohorts associated with an increased risk of COVID-19 hospitalization. Cohort 1 was formed of cases hospitalized with COVID-19 and a set of controls who developed mild symptoms. Cohort 2 included Cohort 1 individuals for whom additional laboratory test data was available. We found several disease signatures where lower levels of lipids were found co-occurring with lower levels of serum calcium and leukocytes. Many of the low lipid signatures were independent of statin use and 50% of cases with hypocalcemia signatures were reported with vitamin D deficiency. These signatures may be attributed to similar mechanisms linking calcium and lipid signaling where changes in cellular lipid levels during inflammation and infection affect calcium signaling in host cells. This study and our previous genomics analysis demonstrate that combinatorial analysis can identify disease signatures associated with the risk of developing severe COVID-19 separately from genomic or clinical data in different populations. Both studies suggest associations between calcium and lipid signaling in severe COVID-19.

COVID 19: Camostat and The Role of Serine Protease Entry Inhibitor TMPRSS2

2020 ◽  
Author(s):  
Stefan Bittmann
Keyword(s):  
Host Cell ◽  
Serine Protease ◽  
Cellular Protein ◽  
Host Cells ◽  
The Novel ◽  
Robert Koch Institute ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

According to the latest research, the novel coronavirus uses the protein angiotensin-converting enzyme 2 (ACE-2) as a receptor for docking to the host cell. Essential for entry is the priming of the spike (S) protein of the virus by host cell proteases. A broadly based team led by infection biologists from the German Primate Centre and with the participation of the Charité Hospital in Berlin, the Hanover Veterinary University Foundation, the BG-UnfallklinikMurnau, the LMU Munich, the Robert Koch Institute and the German Centre for Infection Research wanted to find out how SARS-CoV-2 enters host cells and how this process can be blocked [1]. They have published their findings in the journal "Cell" [1]. The team of scientists was initially able to confirm that SARS-CoV-2 docks to the host cell via the ACE-2 receptor. They also identified Transmembrane serine protease 2 (TMPRSS2) as the cellular protein responsible for entry into the cell [1-3].

scholarly journals The potential role of Bromhexine in the management of COVID-19: Decipher and a real game-changer

2021 ◽  
Vol 5 (01) ◽  
pp. 1-4
Author(s):  
Hayder M. Al-Kuraishy ◽  
Marwa S. Al-Niemi ◽  
Nawar R. Hussain ◽  
Ali I. Al-Gareeb ◽  
Claire Lugnier
Keyword(s):  
Potential Role ◽  
Host Cells ◽  
Bronchial Epithelial ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease ◽  
Game Changer

Primary infection of SARS-CoV-2 (novel coronavirus or 2019-nCoV), which leads to Covid-19, targets specific cells, such as nasal, bronchial epithelial and pneumocytes, through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Also, type 2 transmembrane serine protease (TMPRSS2) present in the host cell promotes viral uptake by cleaving ACE2 and triggering the SARS-CoV-2 S protein, which facilitates SARS-CoV-2 entry into host cells. One of the TMPRSS2 inhibitors with a greater distribution capacity into the lung tissue is bromhexine hydrochloride which attenuates the entry and proliferation of SARS-CoV-2. Bromhexine is an effective drug in the management and treatment of Covid-19 pneumonia via targeting ACE2/ TMPRSS2 pathway. However, prospective and controlled clinical trials are recommended to confirm this observation.

scholarly journals Testosterone Deficiency Is a Risk Factor for Severe COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Lukas Lanser ◽  
Francesco Robert Burkert ◽  
Lis Thommes ◽  
Alexander Egger ◽  
Gregor Hoermann ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Sex Hormones ◽  
Immune Activation ◽  
Clinical Manifestations ◽  
Morbidity And Mortality ◽  
University Hospital ◽  
Testosterone Levels ◽  
Immune System Activation ◽  
Increased Risk ◽  
The Impact

BackgroundMale sex is related to increased COVID-19 severity and fatality although confirmed infections are similarly distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19.Patients and MethodsWe studied for effects of sex hormones on disease severity and immune activation in 377 patients (230 men, 147 women) with PCR-confirmed SARS-CoV-2 infections hospitalized at the Innsbruck University Hospital between February and December 2020.ResultsMen had more severe COVID-19 with concomitant higher immune system activation upon hospital admission when compared to women. Men with a severe course of infection had lower serum total testosterone (tT) levels whereas luteinizing hormone (LH) and estradiol (E2) levels were within the normal range. tT deficiency was associated with elevated CRP (rs = - 0.567, p &lt; 0.001), IL-6 levels (rs = - 0.563, p &lt; 0.001), lower cholesterol levels (rs = 0.407, p &lt; 0.001) and an increased morbidity and mortality. Men with tT levels &lt; 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 – 144.639], p = 0.006) compared to men with tT levels &gt; 230 ng/dL. Moreover, while morbidity and mortality showed a positive correlation with E2 levels at admission, we detected a negative correlation with the tT/E2 ratio upon hospital admission.ConclusionHospitalized men with COVID-19 present with rather low testosterone levels linked to more advanced immune activation, severe clinical manifestations translating into an increased risk for ICU admission or death. The underlying mechanisms remain elusive but may include infection driven hypogonadism as well as inflammation mediated cholesterol reduction causing gonadotropin suppression and impaired androgen formation. Finally, in elderly late onset hypogonadism might also contribute to lower testosterone levels.

scholarly journals Combinatorial analysis of phenotypic and clinical risk factors associated with hospitalized COVID-19 patients

2021 ◽  
Author(s):  
Sayoni Das ◽  
Matthew Pearson ◽  
Krystyna Taylor ◽  
Veronique Bouchet ◽  
Gert Lykke Møller ◽  
...  
Keyword(s):  
Risk Factors ◽  
Severe Disease ◽  
Host Cells ◽  
Combinatorial Analysis ◽  
Phenotypic Data ◽  
Factors Associated ◽  
Lipid Signalling ◽  
Increased Risk ◽  
Different Populations ◽  
Disease Signatures

1AbstractCharacterization of the risk factors associated with variability in the clinical outcomes of COVID-19 is important. Our previous study using genomic data identified a potential role of calcium and lipid homeostasis in severe COVID-19. This study aimed to identify similar combinations of features (disease signatures) associated with severe disease in a separate patient population with purely clinical and phenotypic data.The PrecisionLife combinatorial analytics platform was used to analyze features derived from de-identified health records in the UnitedHealth Group COVID-19 Data Suite. The platform identified and analyzed 836 disease signatures in two cohorts associated with increased risk of COVID-19 hospitalization. Cohort 1 was formed of cases hospitalized with COVID-19 and a set of controls who developed mild symptoms. Cohort 2 included Cohort 1 individuals for whom additional laboratory test data was available.We found several disease signatures where lower levels of lipids were found co-occurring with lower levels of serum calcium and leukocytes. Many of the low lipid signatures were independent of statin use and 50% of cases with hypocalcemia signatures were reported with vitamin D deficiency. These signatures may be attributed to similar mechanisms linking calcium and lipid signaling where changes in cellular lipid levels during inflammation and infection affect calcium signaling in host cells.This study and our previous genomics analysis demonstrate that combinatorial analysis can identify disease signatures associated with the risk of developing severe COVID-19 separately from genomic or clinical data in different populations. Both studies suggest associations between calcium and lipid signalling in severe COVID-19.

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