scholarly journals The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak

2020 ◽  
Author(s):  
Ibrahim Y. Hachim ◽  
Mahmood Y. Hachim ◽  
Iman Mamdouh Talaat ◽  
Vanessa M. López-Ozuna ◽  
Narjes Saheb Sharif-Askari ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Mortality Rates ◽  
Therapeutic Options ◽  
The Novel ◽  
Novel Coronavirus ◽  
Gender Variations ◽  
Epidemiological Characteristics

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

scholarly journals The Molecular Basis of Gender Variations in Mortality Rates Associated With the Novel Coronavirus (COVID-19) Outbreak

2021 ◽  
Vol 8 ◽  
Author(s):  
Ibrahim Y. Hachim ◽  
Mahmood Y. Hachim ◽  
Iman Mamdouh Talaat ◽  
Vanessa M. López-Ozuna ◽  
Narjes Saheb Sharif-Askari ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Mortality Rates ◽  
Pathway Enrichment Analysis ◽  
The Novel ◽  
Differential Outcomes ◽  
Novel Coronavirus ◽  
Gender Variations ◽  
Epidemiological Characteristics

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact among different subpopulations. Emerging evidence from different parts of the world showed that male patients usually had a longer disease course as well as worse outcome compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for more effective and personalized response to this disease outbreak. For that reason, here we investigate the molecular basis of gender variations in mortality rates related to COVID-19 infection. To achieve this, we used publicly available lung transcriptomic data from 141 females and compare it to 286 male lung tissues. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Further analysis using pathway enrichment analysis revealed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (CHM, DDX3X, FGFR3, SFRP2, and NLRP2) in males lungs compared to females. This pathway is believed to be essential for immune response and antimicrobial activity in the lung tissues. In contrast, our results showed an increased upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation in male lungs compared to females. Finally, our results showed a differential expression of genes involved in the immune response including the NLRP2 and PTGDR2 in lung tissues of both genders, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed in both genders during the COVID-19 outbreak. This maybe essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

scholarly journals Cytokine Storms, Evolution, and COVID-19

2021 ◽  
Author(s):  
Joe Alcock ◽  
Alix Masters
Keyword(s):  
Immune Response ◽  
Evolutionary Medicine ◽  
Severe Illness ◽  
Host Immune System ◽  
The Novel ◽  
Cytokine Storm ◽  
Medical Interventions ◽  
Experimental Therapies ◽  
Novel Coronavirus

Abstract Since the identification of severe illness caused by the novel coronavirus SARS-CoV-2, the role of the host immune system in causing disease has attracted widespread attention, along with intense interest in medical interventions that target the host immune response. A wide variety of agents have been proposed to treat a cytokine storm in COVID-19, but so far, only one class of medications, corticosteroids, has proved useful. In recent decades, experimental therapies for cytokine storms have been tried and mostly failed to help patients with severe sepsis and other infections. We summarize this history in order to frame expectations for novel interventions in COVID-19 and to bring an evolutionary medicine perspective to the concept of cytokine storms and their treatment.

scholarly journals Immune response against SARS-CoV-2 variants: the role of neutralization assays

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Alicja Maria Chmielewska ◽  
Anna Czarnota ◽  
Krystyna Bieńkowska-Szewczyk ◽  
Katarzyna Grzyb
Keyword(s):  
Immune Response ◽  
Social Life ◽  
Neutralizing Antibody ◽  
The Novel ◽  
International Scientific Community ◽  
Rapid Spread ◽  
Cost Efficient ◽  
Novel Coronavirus

AbstractSince the emergence of the novel coronavirus SARS-CoV-2 in late 2019, the COVID-19 pandemic has hindered social life and global economic activity. As of July 2021, SARS-CoV-2 has caused over four million deaths. The rapid spread and high mortality of the disease demanded the international scientific community to develop effective vaccines in a matter of months. However, unease about vaccine efficacy has arisen with the spread of the SARS-CoV-2 variants of concern (VOCs). Time- and cost-efficient in vitro neutralization assays are widely used to measure neutralizing antibody responses against VOCs. However, the extent to which in vitro neutralization reflects protection from infection remains unclear. Here, we describe common neutralization assays based on infectious and pseudotyped viruses and evaluate their role in testing neutralizing responses against new SARS-CoV-2 variants. Additionally, we briefly review the recent findings on the immune response elicited by available vaccines against major SARS-CoV-2 variants, including Alpha, Beta, Gamma, and Delta.

SARS-COV2 virus and Coronavirus disease (COVID-19)

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  
Keyword(s):  
Close Contact ◽  
Antiviral Agents ◽  
Health Concern ◽  
The Novel ◽  
Global Public Health ◽  
Fatal Disease ◽  
Mild Disease ◽  
Life Threatening ◽  
Novel Coronavirus

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.

The role and relationship of mindreading and social attunement in HRI – position statements of interdisciplinary researchers. Workshop HRI'20

2020 ◽  
Author(s):  
Agnieszka Wykowska ◽  
Jairo Pérez-Osorio ◽  
Stefan Kopp
Keyword(s):  
Mental States ◽  
Human Robot Interaction ◽  
Human Interaction ◽  
Artificial Agents ◽  
The Novel ◽  
Robot Interaction ◽  
Novel Coronavirus ◽  
Relationship Of ◽  
The Relationship

This booklet is a collection of the position statements accepted for the HRI’20 conference workshop “Social Cognition for HRI: Exploring the relationship between mindreading and social attunement in human-robot interaction” (Wykowska, Perez-Osorio & Kopp, 2020). Unfortunately, due to the rapid unfolding of the novel coronavirus at the beginning of the present year, the conference and consequently our workshop, were canceled. On the light of these events, we decided to put together the positions statements accepted for the workshop. The contributions collected in these pages highlight the role of attribution of mental states to artificial agents in human-robot interaction, and precisely the quality and presence of social attunement mechanisms that are known to make human interaction smooth, efficient, and robust. These papers also accentuate the importance of the multidisciplinary approach to advance the understanding of the factors and the consequences of social interactions with artificial agents.

Enteric Microorganisms in Rheumatoid Diseases: Causative Agents and Possible Mechanisms

1985 ◽  
Vol 48 (6) ◽  
pp. 538-545 ◽  
Author(s):  
DOUGLAS L. ARCHER
Keyword(s):  
Immune Response ◽  
Ankylosing Spondylitis ◽  
Molecular Mechanisms ◽  
Enteric Pathogens ◽  
Gastrointestinal Illness ◽  
Hla B27 ◽  
Causative Agents ◽  
Related Individuals ◽  
Rheumatoid Diseases

The role of foodborne enteric pathogens in the development of three seronegative spondarthropathies (ankylosing spondylitis, Reiter's disease and reactive arthritis) is discussed. Although the prevalence of the HLA-B27 antigen in blood-related individuals suggests a genetic predisposition to these diseases, exogenous environmental factors are also indicated. A clinical profile is given to clarify certain relationships of the seronegative arthropathies. Evidence of the involvement of enteric pathogens in the onset of these conditions following gastrointestinal illness is considered along with the interactions of general and molecular mechanisms of the disease processes and the immune response.

scholarly journals Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Xingyi Guo ◽  
Zhishan Chen ◽  
Yumin Xia ◽  
Weiqiang Lin ◽  
Hongzhi Li
Keyword(s):  
Genetic Variation ◽  
The Novel ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Missense Variants ◽  
Catalytic Metal ◽  
Using Data ◽  
Novel Coronavirus ◽  
Insight Into

Abstract Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

scholarly journals The Immune Response to Tumors as a Tool toward Immunotherapy

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
F. Pandolfi ◽  
R. Cianci ◽  
D. Pagliari ◽  
F. Casciano ◽  
C. Bagalà ◽  
...  
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Cancer Colorectal ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Hematologic Malignancies ◽  
The Novel ◽  
Infiltrating Lymphocytes

Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes.

scholarly journals Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Franck Mauvais-Jarvis ◽  
Sabra L Klein ◽  
Ellis R Levin
Keyword(s):  
Immune Response ◽  
Distress Syndrome ◽  
Immune Dysregulation ◽  
Innate Immune ◽  
The Novel ◽  
Cytokine Storm ◽  
Inflammatory Infiltration ◽  
Biological Sex ◽  
17Β Estradiol ◽  
Novel Coronavirus

Abstract Severe outcomes and death from the novel coronavirus disease 2019 (COVID-19) appear to be characterized by an exaggerated immune response with hypercytokinemia leading to inflammatory infiltration of the lungs and acute respiratory distress syndrome. Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17β-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.

scholarly journals The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1849 ◽  
Author(s):  
Davide Brocco ◽  
Rosalba Florio ◽  
Laura De Lellis ◽  
Serena Veschi ◽  
Antonino Grassadonia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Normal Weight ◽  
Therapeutic Options ◽  
Therapeutic Interventions ◽  
Fat Accumulation ◽  
Adipose Organ ◽  
The Impact

Pancreatic cancer (PC) is a lethal malignancy with rising incidence and limited therapeutic options. Obesity is a well-established risk factor for PC development. Moreover, it negatively affects outcome in PC patients. Excessive fat accumulation in obese, over- and normal-weight individuals induces metabolic and inflammatory changes of adipose tissue microenvironment leading to a dysfunctional adipose “organ”. This may drive the association between abnormal fat accumulation and pancreatic cancer. In this review, we describe several molecular mechanisms that underpin this association at both local and systemic levels. We focus on the role of adipose tissue-derived circulating factors including adipokines, hormones and pro-inflammatory cytokines, as well as on the impact of the local adipose tissue in promoting PC. A discussion on potential therapeutic interventions, interfering with pro-tumorigenic effects of dysfunctional adipose tissue in PC, is included. Considering the raise of global obesity, research efforts to uncover the molecular basis of the relationship between pancreatic cancer and adipose tissue dysfunction may provide novel insights for the prevention of this deadly disease. In addition, these efforts may uncover novel targets for personalized interventional strategies aimed at improving the currently unsatisfactory PC therapeutic options.

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