Gender-based differences in coronavirus disease 2019: Hormonal influencers of severe acute respiratory syndrome coronavirus receptors and immune responses

Coronavirus disease 2019 (COVID-19) became a pandemic due to a high rate of infection by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). People with comorbidities such as cardiovascular diseases, Type II diabetes, and COPD have been having acute symptoms and higher rate of mortality. Further, increased severity and lethality of SARS-CoV-2 infection has been observed among men than in women. SARSCoV-2 infects human cells by binding to angiotensin-converting enzyme 2 (ACE2) through its spike protein (S-Protein). ACE2 is a critical transmembrane protein of the renin-angiotensin-aldosterone system which modulates the cardiovascular system and fluid homeostasis. This article reviews the current knowledge about the mechanisms of sex-based differences that may cause variations in COVID-19 susceptibility and outcomes among males and females. Males have been shown to have a delayed viral clearance due to increased retention of coronavirus as compared to females. Recent studies indicate that a severe infection with SARS-CoV-2 impairs spermatogenesis in males, however, the mechanisms by which SARS-CoV-2 damages testicular cells need more studies. We discuss here the distinctive features such as sex hormone milieu, receptor biology, and immunology that may be responsible for the gender-based differences in the outcome of COVID-19.

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Coronavirus Disease 2019 and the Cerebrovascular‐Cardiovascular Systems: What Do We Know So Far?

Journal of the American Heart Association ◽

10.1161/jaha.120.016793 ◽

2020 ◽

Vol 9 (13) ◽

Cited By ~ 8

Author(s):

Anthony S. Larson ◽

Luis Savastano ◽

Ramanathan Kadirvel ◽

David F. Kallmes ◽

Ameer E. Hassan ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Relevant Literature ◽

Cardiac Injury ◽

Severe Infection ◽

Angiotensin Converting Enzyme 2 ◽

Cardiovascular Tissue ◽

High Affinity ◽

Respiratory Involvement ◽

Cardiovascular Involvement ◽

Coagulation Defects

Abstract The severe acute respiratory syndrome coronavirus 2 pandemic of 2019 to 2020 has resulted in multiple hospitalizations, deaths, and economic hardships worldwide. Although respiratory involvement in patients with coronavirus disease 2019 ( COVID ‐19) is well known, the potential cardiovascular and cerebrovascular manifestations are less understood. We performed a PubMed and Google Scholar search and reviewed relevant literature on COVID ‐19 and cardiovascular system involvement. Severe acute respiratory syndrome coronavirus 2 possesses high affinity for angiotensin‐converting enzyme 2 receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID ‐19 cases. Preexisting cardiovascular and cerebrovascular disease has been shown in previous reports to be a risk factor for severe infection. On the basis of our review of published studies, COVID ‐19 patients may be more likely to experience acute cardiac injury, arrhythmia, coagulation defects, and acute stroke and are likely to have poorer outcomes as a result. As the COVID ‐19 pandemic continues, more data about potential cardiovascular and cerebrovascular manifestations of the disease are required.

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COVID-19 and Liver injury: hepatology perspectives

Clinical Medical Reviews and Reports ◽

10.31579/2690-8794/020 ◽

2020 ◽

Vol 2 (3) ◽

pp. 01-04

Author(s):

Irami Filho

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Severe Acute Respiratory Syndrome ◽

Angiotensin Converting Enzyme ◽

Liver Damage ◽

Clinical Manifestations ◽

Protein S ◽

Clinical Syndrome ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2

SARS-CoV-2, a severe acute respiratory syndrome caused by Coronavirus 2, discovered in 2019 in China, is responsible for the current pandemic declared by the WHO since March 2020. The clinical syndrome caused by Covid-19 has a broad spectrum of severity. The most common clinical manifestations are fever, dry cough, dyspnea, fatigue, and anosmia. The virus binds to receptors for angiotensin-converting enzyme 2 (ECA2) and serine protease TMPRSS2 for protein S initiation, which are expressed not only in the lungs but also in the liver, colonic, esophageal and biliary epithelial cells. In this context, the liver is a potential target for COVID-19 infection. Liver damage occurs during the course and treatment of viral infection in patients with or without previous liver disease. Therefore, the characteristics of liver injury associated with COVID-19 were reviewed based on research related, in the context of the pandemic.

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Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin

Journal of Virology ◽

10.1128/jvi.01085-07 ◽

2007 ◽

Vol 82 (4) ◽

pp. 1899-1907 ◽

Cited By ~ 80

Author(s):

Wuze Ren ◽

Xiuxia Qu ◽

Wendong Li ◽

Zhenggang Han ◽

Meng Yu ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Receptor Binding ◽

Protein S ◽

Cell Entry ◽

Angiotensin Converting Enzyme 2 ◽

Receptor Usage ◽

Virus Origin ◽

Immunodeficiency Virus ◽

Horseshoe Bat ◽

Insert Region

ABSTRACT Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed.

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Interferons and viruses induce a novel primate-specific isoform dACE2 and not the SARS-CoV-2 receptor ACE2

10.1101/2020.07.19.210955 ◽

2020 ◽

Cited By ~ 7

Author(s):

Olusegun O. Onabajo ◽

A. Rouf Banday ◽

Wusheng Yan ◽

Adeola Obajemu ◽

Megan L. Stanifer ◽

...

Keyword(s):

Amino Acids ◽

Tumor Microenvironment ◽

Severe Acute Respiratory Syndrome ◽

Current Knowledge ◽

Spike Protein ◽

Target Cells ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Terminal Amino

ABSTRACTSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, primate-specific isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In vitro, dACE2, which lacks 356 N-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results reconcile current knowledge on ACE2 expression and suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, inflammatory tumor microenvironment, or viral co-infections is unlikely to affect the cellular entry of SARS-CoV-2 and promote infection.

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Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

10.26434/chemrxiv.12186624.v3 ◽

2020 ◽

Author(s):

Cristina Garcia-Iriepa ◽

Cecilia Hognon ◽

Antonio Francés-Monerris ◽

Isabel Iriepa ◽

Tom Miclot ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Molecular Mechanisms ◽

Molecular Design ◽

Binding Free Energy ◽

Transmembrane Protein ◽

Spike Protein ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Rational Molecular Design ◽

Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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COVID-19: a review of current knowledge regarding exposure, quarantine, isolation and other preventive measures

Therapeutic Advances in Infectious Disease ◽

10.1177/20499361211032039 ◽

2021 ◽

Vol 8 ◽

pp. 204993612110320

Author(s):

Robert Rosolanka ◽

Andres F. Henao-Martinez ◽

Larissa Pisney ◽

Carlos Franco-Paredes ◽

Martin Krsak

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Clinical Response ◽

Preventive Measures ◽

Current Knowledge ◽

Therapeutic Options ◽

Exposure Control ◽

Knowledge Gaps ◽

Vaccination Strategies ◽

Speed Up

Deeper understanding of the spread, morbidity, fatality, and development of immune response associated with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is necessary in order to establish an appropriate epidemiological and clinical response. Exposure control represents a key part of the combat against COVID-19, as the effectiveness of current therapeutic options remains partial. Since the preventive measures have not been sufficiently able to slow down this pandemic, in this article we explore some of the pertinent knowledge gaps, while overall looking to effective vaccination strategies as a way out. Early on, such strategies may need to rely on counting the convalescents as protected in order to speed up the immunization of the whole population.

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High-Intensity Focused Ultrasound Circular Cyclocoagulation in Glaucoma: A Step Forward for Cyclodestruction?

Journal of Ophthalmology ◽

10.1155/2017/7136275 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Rodolfo Mastropasqua ◽

Vincenzo Fasanella ◽

Alessandra Mastropasqua ◽

Marco Ciancaglini ◽

Luca Agnifili

Keyword(s):

High Intensity ◽

Ciliary Body ◽

Focused Ultrasound ◽

Current Knowledge ◽

High Intensity Focused Ultrasound ◽

High Rate ◽

Dose Effect ◽

Computer Assisted ◽

Refractory Glaucoma ◽

High Level

The ciliary body ablation is still considered as a last resort treatment to reduce the intraocular pressure (IOP) in uncontrolled glaucoma. Several ablation techniques have been proposed over the years, all presenting a high rate of complications, nonselectivity for the target organ, and unpredictable dose-effect relationship. These drawbacks limited the application of cyclodestructive procedures almost exclusively to refractory glaucoma. High-intensity focused ultrasound (HIFU), proposed in the early 1980s and later abandoned because of the complexity and side effects of the procedure, was recently reconsidered in a new approach to destroy the ciliary body. Ultrasound circular cyclocoagulation (UC3), by using miniaturized transducers embedded in a dedicated circular-shaped device, permits to selectively treat the ciliary body in a one-step, computer-assisted, and non-operator-dependent procedure. UC3 shows a high level of safety along with a predictable and sustained IOP reduction in patients with refractory glaucoma. Because of this, the indication of UC3 was recently extended also to naïve-to-surgery patients, thus reconsidering the role and timing of ciliary body ablation in the surgical management of glaucoma. This article provides a review of the most used cycloablative techniques with particular attention to UC3, summarizing the current knowledge about this procedure and future possible developments.

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Severe acute respiratory syndrome (SARS) related coronavirus in bats

Animal Diseases ◽

10.1186/s44149-021-00004-w ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Rong Geng ◽

Peng Zhou

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Current Knowledge ◽

Disease Outbreaks ◽

First Century ◽

Intermediate Hosts ◽

Human Coronavirus ◽

Transmission Potential ◽

Disease Agent ◽

And Control ◽

Genomic Similarity

AbstractThree major human coronavirus disease outbreaks, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and 2019 coronavirus disease (COVID-19), occurred in the twenty-first century and were caused by different coronaviruses (CoVs). All these viruses are considered to have originated from bats and transmitted to humans through intermediate hosts. SARS-CoV-1 and SARS-CoV-2, disease agent of COVID-19, shared around 80% genomic similarity, and thus belong to SARS-related CoVs. As a natural reservoir of viruses, bats harbor numerous other SARS-related CoVs that could potentially infect humans around the world, causing SARS or COVID-19 like outbreaks in the future. In this review, we summarized the current knowledge of CoVs on geographical distribution, genetic diversity, cross-species transmission potential and possible pathogenesis in humans, aiming for a better understanding of bat SARS-related CoVs in the context of prevention and control.

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Do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression explain increased severity and mortality of COVID-19 in males?

Diagnosis ◽

10.1515/dx-2020-0054 ◽

2020 ◽

Vol 7 (4) ◽

pp. 385-386 ◽

Cited By ~ 3

Author(s):

Jens Vikse ◽

Giuseppe Lippi ◽

Brandon Michael Henry

Keyword(s):

Mortality Rate ◽

Severe Acute Respiratory Syndrome ◽

Lung Injury ◽

Angiotensin Converting Enzyme ◽

Converting Enzyme ◽

Sars Coronavirus ◽

Immunomodulatory Treatment ◽

Angiotensin Converting Enzyme 2 ◽

Cytopathic Effects ◽

Severe Lung

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

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A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies

Journal of General Virology ◽

10.1099/vir.0.80844-0 ◽

2005 ◽

Vol 86 (5) ◽

pp. 1435-1440 ◽

Cited By ~ 65

Author(s):

Milosz Faber ◽

Elaine W. Lamirande ◽

Anjeanette Roberts ◽

Amy B. Rice ◽

Hilary Koprowski ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Protein S ◽

S Protein ◽

Cellular Immune Responses ◽

Glycoprotein G ◽

Cellular Immune ◽

Animal Reservoirs ◽

S Genes

Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.

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