scholarly journals Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies

2020 ◽  
Vol 7 ◽  
Author(s):  
Thushara Galbadage ◽  
Brent M. Peterson ◽  
Jeffrey S. Wang ◽  
Avishka Jayasekara ◽  
Danny A. Ramirez ◽  
...  
Keyword(s):  
Risk Factor ◽  
Viral Entry ◽  
Targeted Therapies ◽  
Molecular Mechanisms ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Epidemiological Studies ◽  
Endocrine Regulation ◽  
Regulatory Systems ◽  
Males And Females

Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2019 (COVID-19). Currently, there are no guidelines or protocols to help alter the course of sex-specific COVID-19 prognosis, especially in severe disease presentations. This is partly due to the lack of research studies characterizing the differences in male vs. female host response to the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and a lack of a well-rounded understanding of the molecular mechanisms involved. Here, we discuss three distinct but interconnected molecular-level differences in males and females that likely play an essential role in the COVID-19 prognosis. We review interactions of SARS-CoV-2 with host cell angiotensin-converting enzyme 2 (ACE2) in the viral entry between males vs. females and discuss the differential regulation of the renin-angiotensin system (RAS) between the two sexes. Next, we present immune response disparities and how immune function and endocrine regulation may render males increasingly vulnerable to severe COVID-19. We describe the interconnected roles of these three regulatory systems in males and females in response to SARS-CoV-2 infection. Finally, we highlight the clinical implications of these mechanisms to patients with COVID-19 and propose putative targeted therapies that can help reduce COVID-19 severity in those critically ill.

COVID-19 and diabetes mellitus: potential metabolic associations

2021 ◽  
Vol 21 ◽  
Author(s):  
Pedro Henrique Abreu da Silva ◽  
Andressa Santos Garcia ◽  
Fábio Aguiar Alves ◽  
André Luis Souza dos Santos ◽  
Cátia Lacerda Sodré
Keyword(s):  
Diabetes Mellitus ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Renin Angiotensin System ◽  
Cell Receptor ◽  
Protective Role ◽  
Infection Process ◽  
Point Of View ◽  
Diabetic Patients ◽  
Viral Binding

: The COVID-19 pandemic turned the SARS-CoV-2 into the main target of scientific research all around the world. Many advances have already been made, but there is still a long way to go to solve the molecular mechanisms related to the process of the SARS-CoV-2 infection, as well as the particularities of the disease, its course and the complex host-pathogen relationships. However, a lot has been theorized and associated with COVID-19, like the worst prognosis of the disease among individuals with some comorbidities, like diabetes mellitus. In this perspective, diabetic patients are repeatedly associated with more severe cases of COVID-19 when compared to non-diabetic patients. Even though ACE2 (angiotensin-converting enzyme 2) was recognized as the host cell receptor for both binding and entering of SARS-CoV-2 particles, it was also pointed out that this enzyme plays an important protective role against pulmonary damage. Therefore, paradoxically as it may seem, the low baseline level of this receptor in people with diabetes is directly linked to a more expressive loss of ACE2 protective effect, which could be one of the possible factors for the worst prognosis of COVID-19. Still, COVID-19 may also have a diabetogenic effect. From this point of view, the main topics that will be highlighted are (i) the mechanism of the viral entry, with special attention to the cellular receptor (ACE2) and the viral binding protein (spike), (ii) the relationship among the renin-angiotensin system, the infection process and the patients' prognosis, (iii) the glucose control and the medicines used in this event, and (iv) a brief analysis on diabetes triggered by COVID-19.

scholarly journals Innate immunology in COVID-19—a living review. Part I: viral entry, sensing and evasion

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Clarissa Coveney ◽  
Michel Tellier ◽  
Fangfang Lu ◽  
Shayda Maleki-Toyserkani ◽  
Ruth Jones ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Severe Disease ◽  
World Health ◽  
Health Concern ◽  
Viral Immunity ◽  
Restriction Factors ◽  
Innate Immunology ◽  
Host Restriction

Abstract The coronavirus infectious disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a world health concern and can cause severe disease and high mortality in susceptible groups. While vaccines offer a chance to treat disease, prophylactic and anti-viral treatments are still of vital importance, especially in context of the mutative ability of this group of viruses. Therefore, it is essential to elucidate the molecular mechanisms of viral entry, innate sensing and immune evasion of SARS-CoV-2, which control the triggers of the subsequent excessive inflammatory response. Viral evasion strategies directly target anti-viral immunity, counteracting host restriction factors and hijacking signalling pathways to interfere with interferon production. In Part I of this review, we examine SARS-CoV-2 viral entry and the described immune evasion mechanisms to provide a perspective on how the failure in initial viral sensing by infected cells can lead to immune dysregulation causing fatal COVID-19, discussed in Part II.

scholarly journals The Impact of Work Hours on Depressive Symptoms among Koreans Aged 45 and Over

2021 ◽  
Vol 18 (3) ◽  
pp. 853
Author(s):  
Juyeong Kim ◽  
Eun-Cheol Park
Keyword(s):  
Older Adults ◽  
Depressive Symptoms ◽  
Social Services ◽  
Depression Scale ◽  
Epidemiological Studies ◽  
Work Hours ◽  
Middle Aged ◽  
Health Studies ◽  
Males And Females ◽  
The Impact

Background: Given the documented importance of employment for middle-aged and older adults’ mental health, studies of the association between their number of work hours and depressive symptoms are needed. Objectives: To examine the association between the number of work hours and depressive symptoms in Korean aged 45 and over. Methods: We used data from the first wave to fourth wave of the Korea Longitudinal Study of Aging. Using the first wave at baseline, data included 9845 individuals. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression scale. We performed a longitudinal analysis to estimate the prevalence of depressive symptoms by work hours. Results: Both unemployed males and females aged 45–65 years were associated with higher depressive symptoms (β = 0.59, p < 0.001; β = 0.32, p < 0.001). Females working ≥ 69 h were associated with higher depressive symptoms compared to those working 41–68 h (β = 0.25, p = 0.013). Among those both middle-aged and older adults, both males and females unemployed were associated with higher depressive symptoms. Those middle-aged female working ≥69 h were associated with higher depressive symptoms. Conclusions: An increase in depressive symptoms was associated with unemployed males and females working ≥69 h compared to those working 41–68 h. Although this association was found among middle-aged individuals, a decrease in depressive symptoms in both sexes was associated with working 1–40 h. Depressive symptoms should decrease by implementing employment policies and social services to encourage employers to support middle-aged and older adults in the workforce considering their sex and age differences.

scholarly journals Obesity as a Risk Factor for Severe COVID-19 and Complications: A Review

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 933
Author(s):  
Fien Demeulemeester ◽  
Karin de Punder ◽  
Marloes van Heijningen ◽  
Femke van Doesburg
Keyword(s):  
Risk Factor ◽  
Disease Severity ◽  
Viral Entry ◽  
Thrombus Formation ◽  
Clinical Findings ◽  
High Risk Group ◽  
Therapeutic Interventions ◽  
Cytokine Storm ◽  
Negative Consequences ◽  
Major Complications

Emerging data suggest that obesity is a major risk factor for the progression of major complications such as acute respiratory distress syndrome (ARDS), cytokine storm and coagulopathy in COVID-19. Understanding the mechanisms underlying the link between obesity and disease severity as a result of SARS-CoV-2 infection is crucial for the development of new therapeutic interventions and preventive measures in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe COVID-19 and complications. First, viral entry can be facilitated by the upregulation of viral entry receptors, like angiotensin-converting enzyme 2 (ACE2), among others. Second, obesity-induced chronic inflammation and disruptions of insulin and leptin signaling can result in impaired viral clearance and a disproportionate or hyper-inflammatory response, which together with elevated ferritin levels can be a direct cause for ARDS and cytokine storm. Third, the negative consequences of obesity on blood coagulation can contribute to the progression of thrombus formation and hemorrhage. In this review we first summarize clinical findings on the relationship between obesity and COVID-19 disease severity and then further discuss potential mechanisms that could explain the risk for major complications in patients suffering from obesity.

scholarly journals SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

2021 ◽  
Vol 11 (5) ◽  
pp. 431
Author(s):  
Sabine Hofer ◽  
Norbert Hofstätter ◽  
Albert Duschl ◽  
Martin Himly
Keyword(s):  
Risk Factor ◽  
Particle Deposition ◽  
Early Stage ◽  
Severe Disease ◽  
Ambient Air ◽  
Aerosol Deposition ◽  
Pulmonary Involvement ◽  
Mild Disease ◽  
Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

scholarly journals The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

2021 ◽  
Vol 18 (9) ◽  
pp. 5038
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Maria Clara La Rosa ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pilot Study ◽  
Alcohol Consumption ◽  
Telomere Length ◽  
Molecular Mechanisms ◽  
Epidemiological Studies ◽  
Potential Association ◽  
Significant Difference ◽  
Periconceptional Period ◽  
Using Data

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

scholarly journals Assessment of new-onset depression and anxiety associated with COVID-19

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Eman Hurissi ◽  
Ethar Abu-jabir ◽  
Amnah Mohammed ◽  
Mashael Mahnashi ◽  
Sana Alharbi ◽  
...  
Keyword(s):  
Epidemiological Studies ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Online Questionnaire ◽  
Final Sample ◽  
Significant Difference ◽  
Patient Health ◽  
Males And Females ◽  
Arabian Population ◽  
New Onset

Abstract Background Psychological disorders are common among individuals who experienced COVID-19. Previous studies have shown that females report higher depression and anxiety than males. The present study aims to test the differences in depression and anxiety between males and females who have experienced COVID-19. This a descriptive, observational, comparative study, among Saudi Arabian population. A total of 686 participants have been recruited. Participants completed an online questionnaire that contains questions about sociodemographic, COVID-19, Generalized Anxiety Disorder (GAD-7) questionnaire, and Patient Health Questionnaire (PHQ-9) to measure anxiety and depression, respectively. Results Twenty-six percent of the participants were excluded and our final sample consisted of 507 participants (median age 23; 65% females). Of the final sample, 23% (118) have been previously diagnosed with COVID-19. There is no significant difference in GAD-7 and PHQ-9 scores between COVID-19- positive and COVID-19-negative populations. However, females who have experienced COVID-19 reported significantly higher GAD-7 and PHQ-9 scores compared to males. Conclusion The results of our study show that females are significantly at a higher risk for depression and anxiety as a result of COVID-19 infection compared to males. Further epidemiological studies are required for a better understanding of this correlation.

scholarly journals High-resolution view of HIV-1 reverse transcriptase initiation complexes and inhibition by NNRTI drugs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Betty Ha ◽  
Kevin P. Larsen ◽  
Jingji Zhang ◽  
Ziao Fu ◽  
Elizabeth Montabana ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Viral Entry ◽  
Reverse Transcription ◽  
Molecular Mechanisms ◽  
Dissociation Kinetics ◽  
Structural Mechanism ◽  
Medium Resolution ◽  
Kinetics Of ◽  
Hiv 1

AbstractReverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon viral entry, HIV-1 reverse transcriptase (RT) initiates from a host tRNALys3 primer bound to the vRNA genome and is the target of key antivirals, such as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Initiation proceeds slowly with discrete pausing events along the vRNA template. Despite prior medium-resolution structural characterization of reverse transcriptase initiation complexes (RTICs), higher-resolution structures of the RTIC are needed to understand the molecular mechanisms that underlie initiation. Here we report cryo-EM structures of the core RTIC, RTIC–nevirapine, and RTIC–efavirenz complexes at 2.8, 3.1, and 2.9 Å, respectively. In combination with biochemical studies, these data suggest a basis for rapid dissociation kinetics of RT from the vRNA–tRNALys3 initiation complex and reveal a specific structural mechanism of nucleic acid conformational stabilization during initiation. Finally, our results show that NNRTIs inhibit the RTIC and exacerbate discrete pausing during early reverse transcription.

scholarly journals Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. Flook ◽  
C. Jackson ◽  
E. Vasileiou ◽  
C. R. Simpson ◽  
M. D. Muckian ◽  
...  
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Systematic Review ◽  
At Risk ◽  
Risk Factor ◽  
Disease Severity ◽  
Severe Disease ◽  
Public Health Response ◽  
Wide Range ◽  
Multivariable Analyses

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

scholarly journals SARS-CoV-2 and Obesity: “CoVesity”—a Pandemic Within a Pandemic

2021 ◽  
Author(s):  
Kimberley Zakka ◽  
◽  
Swathikan Chidambaram ◽  
Sami Mansour ◽  
Kamal Mahawar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Viral Load ◽  
Respiratory Failure ◽  
Health Outcomes ◽  
Severe Disease ◽  
Vulnerable Population ◽  
Low Grade ◽  
Obesity Management ◽  
Low Grade Inflammation

AbstractIndividuals who are overweight or suffering from obesity are in a chronic state of low-grade inflammation, making them particularly susceptible to developing severe forms of respiratory failure. Studies conducted in past pandemics link obesity with worse health outcomes. This population is thus of particular concern within the context of the COVID-19 pandemic, considering the cessation of obesity management services. This systematic review highlights [1] the reciprocal link between the obesity and COVID-19 pandemics, [2] obesity as a risk factor for more severe disease in past pandemics, [3] potential mechanisms that make individual’s suffering from obesity more susceptible to severe disease and higher viral load, and [4] the need to safely resume bariatric services as recommended by expert guidelines, in order to mitigate the health outcomes of an already vulnerable population.

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