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The Renin-Angiotensin System (RAS) in COVID-19 Disease: Where We Are 3 Years after the Beginning of the Pandemic.
Prato, M, Tiberti, N, Mazzi, C, Gobbi, F, Piubelli, C, Longoni, SS
Microorganisms. 2024;(3)
Abstract
The RAS is a hormonal system playing a pivotal role in the control of blood pressure and electrolyte homeostasis, the alteration of which is associated with different pathologies, including acute respiratory distress syndrome (ARDS). As such, it is not surprising that a number of studies have attempted to elucidate the role and balance of the renin-angiotensin system (RAS) in COVID-19. In this review article, we will describe the evidence collected regarding the two main enzymes of the RAS (i.e., ACE and ACE2) and their principal molecular products (i.e., AngII and Ang1-7) in SARS-CoV-2 infection, with the overarching goal of drawing conclusions on their possible role as clinical markers in association with disease severity, progression, and outcome. Moreover, we will bring into the picture new experimental data regarding the systemic activity of ACE and ACE2 as well as the concentration of AngII and Ang1-7 in a cohort of 47 COVID-19 patients hospitalized at the IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy) between March and April 2020. Finally, we will discuss the possibility of considering this systemic pathway as a clinical marker for COVID-19.
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The Ongoing Impact of COVID-19 on Pediatric Obesity.
Iacopetta, D, Catalano, A, Ceramella, J, Pellegrino, M, Marra, M, Scali, E, Sinicropi, MS, Aquaro, S
Pediatric reports. 2024;(1):135-150
Abstract
In the developed world, pediatric obesity (PO) has been a major health concern since the last century, and this condition may lead to detrimental life-long physical and mental comorbidities. Currently, its prevalence has increased in low- and middle-income countries and in many high-income countries. Thus, the provision of effective and tailored care for children and their families has become vital. The social consequences of the COVID-19 pandemic are known everywhere, and among these, it has been argued that the COVID-19 pandemic has had a major impact on PO. Overall, the growth of PO over the last decade has been enhanced by the pandemic. During the COVID-19 pandemic, children, adolescents and young adults gained weight as the pediatric population dealt with sedentary lifestyles and changes in food habits. In this review, we want to highlight the impact that the COVID-19 pandemic had on PO.
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Molecular cross-talk between long COVID-19 and Alzheimer's disease.
Pszczołowska, M, Walczak, K, Misków, W, Antosz, K, Batko, J, Karska, J, Leszek, J
GeroScience. 2024;(3):2885-2899
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Abstract
The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some of its symptoms affect the nervous system and resemble symptoms of Alzheimer's disease (AD)-a neurodegenerative condition caused by the accumulation of amyloid beta and hyperphosphorylation of tau proteins. Multiple studies have found dependence between these two conditions. Patients with Alzheimer's disease have a greater risk of SARS-CoV-2 infection due to increased levels of angiotensin-converting enzyme 2 (ACE2), and the infection itself promotes amyloid beta generation which enhances the risk of AD. Also, the molecular pathways are alike-misregulations in folate-mediated one-carbon metabolism, a deficit of Cq10, and disease-associated microglia. Medical imaging in both of these diseases shows a decrease in the volume of gray matter, global brain size reduction, and hypometabolism in the parahippocampal gyrus, thalamus, and cingulate cortex. In some studies, a similar approach to applied medication can be seen, including the use of amino adamantanes and phenolic compounds of rosemary. The significance of these connections and their possible application in medical practice still needs further study but there is a possibility that they will help to better understand long COVID.
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Phytoimmunomodulators: A review of natural modulators for complex immune system.
Hooda, P, Malik, R, Bhatia, S, Al-Harrasi, A, Najmi, A, Zoghebi, K, Halawi, MA, Makeen, HA, Mohan, S
Heliyon. 2024;(1):e23790
Abstract
In the past few decades, the medicinal properties of plants and their effects on the human immune system are being studied extensively. Plants are an incredible source of traditional medicines that help cure various diseases, including altered immune mechanisms and are economical and benign compared to allopathic medicines. Reported data in written documents such as Traditional Chinese medicine, Indian Ayurvedic medicine support the supplementation of botanicals for immune defense reactions in the body and can lead to safe and effective immunity responses. Additionally, some botanicals are well-identified as magical herbal remedies because they act upon the pathogen directly and help boost the immunity of the host. Chemical compounds, also known as phytochemicals, obtained from these botanicals looked promising due to their effects on the human immune system by modulating the lymphocytes which subsequently reduce the chances of getting infected. This paper summarises most documented phytochemicals and how they act on the immune system, their properties and possible mechanisms, screening conventions, formulation guidelines, comparison with synthetic immunity-enhancers, marketed immunity-boosting products, and immune-booster role in the ongoing ghastly corona virus wave. However, it focuses mainly on plant metabolites as immunomodulators. In addition, it also sheds light on the current advancements and future possibilities in this field. From this thorough study, it can be stated that the plant-based secondary metabolites contribute significantly to immunity building and could prove to be valuable medicaments for the design and development of novel immunomodulators even for a pandemic like COVID-19.
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COVID-19-Associated Rhinocerebral Mucormycosis, an Incidental Finding or a Matter of Concern - Mixed-Method Systematic Review.
Andreescu, M, Moldovan, C, Lespezeanu, DA, Mocanu, AI, Schipor, MA, Mocanu, H
Infection and drug resistance. 2024;:387-402
Abstract
With the advent of COVID-19, the number of patients diagnosed with mucormycosis has increased, especially in developing countries. The reason behind this increase is that COVID-19 causes hypoxia that promotes the growth of fungus. To identify the association between mucormycosis and COVID-19, in critically ill or immunocompromised COVID-19 patients. The literature included in the review was researched from October 1, 2021, to November 1, 2022, by using the Google Scholar database as the search engine. Of the 20 articles included, there were 4 case reports, 2 case series, 10 narrative reviews, and 4 quantitative studies. Mucormycetes growth is caused by several factors, including hyperglycemia owing to previously existing diabetes or excessive use of steroids, increased ferritin levels owing to the inflammatory cascade initiated by COVID-19, and immunosuppression caused by the use of steroids or other immunosuppressive therapy. Reduced white-cell count and activity in COVID-19 leads to increased germination of fungal spores hence developing a catastrophic picture of rhinocerebral mucormycosis. Considering that the hematological patient is frequently treated with cortisone, immunosuppressed due to the underlying condition, but also through the administered therapy, the association with a possible diabetes makes this patient susceptible to developing rhinocerebral mucormycosis during COVID-19 infection. Despite being severe, the association between mucormycosis and COVID-19 is specific and treatable. Development of mucormycosis in hematological patients suffering from severe COVID-19 disease is dangerous, yet not compulsory and can be prevented. Using a common steroid-dose protocol with hyperbaric oxygen and necessary preventive measure reveals the disease as a superadded infection. Hypoxia, poor glycemic control and overuse of steroids or immunosuppressive drugs cause it.
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Field based research in the era of the pandemic in resource limited settings: challenges and lessons for the future.
Mulchandani, R, Lyngdoh, T, Gandotra, S, Isser, HS, Dhamija, RK, Kakkar, AK
Frontiers in public health. 2024;:1309089
Abstract
The coronavirus pandemic that began in December 2019, has had an unprecedented impact on the global economy, health systems and infrastructure, in addition to being responsible for significant mortality and morbidity worldwide. The "new normal" has brought along, unforeseen challenges for the scientific community, owing to obstructions in conducting field-based research in lieu of minimizing exposure through in-person contact. This has had greater ramifications for the LMICs, adding to the already existing concerns. As a response to COVID-19 related movement restrictions, public health researchers across countries had to switch to remote data collections methods. However, impediments like lack of awareness and skepticism among participants, dependence on paper-based prescriptions, dearth of digitized patient records, gaps in connectivity, reliance on smart phones, concerns with participant privacy at home and greater loss to follow-up act as hurdles to carrying out a research study virtually, especially in resource-limited settings. Promoting health literacy through science communication, ensuring digitization of health records in hospitals, and employing measures to encourage research participation among the general public are some steps to tackle barriers to remote research in the long term. COVID-19 may not be a health emergency anymore, but we are not immune to future pandemics. A more holistic approach to research by turning obstacles into opportunities will not just ensure a more comprehensive public health response in the coming time, but also bolster the existing infrastructure for a stronger healthcare system for countries.
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Molecular mechanisms of dexamethasone actions in COVID-19: Ion channels and airway surface liquid dynamics.
Harvey, BJ
Steroids. 2024;:109348
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Abstract
The COVID-19 pandemic has been a global health crisis of unprecedented magnitude. In the battle against the SARS-CoV-2 coronavirus, dexamethasone, a widely used corticosteroid with potent anti-inflammatory properties, has emerged as a promising therapy in the fight against severe COVID-19. Dexamethasone is a synthetic glucocorticoid that exerts its therapeutic effects by suppressing the immune system and reducing inflammation. In the context of COVID-19, the severe form of the disease is often characterized by a hyperactive immune response, known as a cytokine storm. Dexamethasone anti-inflammatory properties make it a potent tool in modulating this exaggerated immune response. Lung inflammation may lead to excessive fluid accumulation in the airways which can reduce gas exchange and mucociliary clearance. Pulmonary oedema and flooding of the airways are hallmarks of severe COVID-19 lung disease. The volume of airway surface liquid is determined by a delicate balance of salt and water secretion and absorption across the airway epithelium. In addition to its anti-inflammatory actions, dexamethasone modulates the activity of ion channels which regulate electrolyte and water transport across the airway epithelium. The observations of dexamethasone activation of sodium ion absorption via ENaC Na+ channels and inhibition of chloride ion secretion via CFTR Cl- channels to decrease airway surface liquid volume indicate a novel therapeutic action of the glucocorticoid to reverse airway flooding. This brief review delves into the early non-genomic and late genomic signaling mechanisms of dexamethasone regulation of ion channels and airway surface liquid dynamics, shedding light on the molecular mechanisms underpinning the action of the glucocorticoid in managing COVID-19.
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COVID-19 and Bone Loss: A Review of Risk Factors, Mechanisms, and Future Directions.
Creecy, A, Awosanya, OD, Harris, A, Qiao, X, Ozanne, M, Toepp, AJ, Kacena, MA, McCune, T
Current osteoporosis reports. 2024;(1):122-134
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Abstract
PURPOSE OF REVIEW SARS-CoV-2 drove the catastrophic global phenomenon of the COVID-19 pandemic resulting in a multitude of systemic health issues, including bone loss. The purpose of this review is to summarize recent findings related to bone loss and potential mechanisms. RECENT FINDINGS The early clinical evidence indicates an increase in vertebral fractures, hypocalcemia, vitamin D deficiencies, and a loss in BMD among COVID-19 patients. Additionally, lower BMD is associated with more severe SARS-CoV-2 infection. Preclinical models have shown bone loss and increased osteoclastogenesis. The bone loss associated with SARS-CoV-2 infection could be the result of many factors that directly affect the bone such as higher inflammation, activation of the NLRP3 inflammasome, recruitment of Th17 cells, the hypoxic environment, and changes in RANKL/OPG signaling. Additionally, SARS-CoV-2 infection can exert indirect effects on the skeleton, as mechanical unloading may occur with severe disease (e.g., bed rest) or with BMI loss and muscle wasting that has also been shown to occur with SARS-CoV-2 infection. Muscle wasting can also cause systemic issues that may influence the bone. Medications used to treat SARS-CoV-2 infection also have a negative effect on the bone. Lastly, SARS-CoV-2 infection may also worsen conditions such as diabetes and negatively affect kidney function, all of which could contribute to bone loss and increased fracture risk. SARS-CoV-2 can negatively affect the bone through multiple direct and indirect mechanisms. Future work will be needed to determine what patient populations are at risk of COVID-19-related increases in fracture risk, the mechanisms behind bone loss, and therapeutic options. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.
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Changes to Public Health Surveillance Methods Due to the COVID-19 Pandemic: Scoping Review.
Clark, EC, Neumann, S, Hopkins, S, Kostopoulos, A, Hagerman, L, Dobbins, M
JMIR public health and surveillance. 2024;:e49185
Abstract
BACKGROUND Public health surveillance plays a vital role in informing public health decision-making. The onset of the COVID-19 pandemic in early 2020 caused a widespread shift in public health priorities. Global efforts focused on COVID-19 monitoring and contact tracing. Existing public health programs were interrupted due to physical distancing measures and reallocation of resources. The onset of the COVID-19 pandemic intersected with advancements in technologies that have the potential to support public health surveillance efforts. OBJECTIVE This scoping review aims to explore emergent public health surveillance methods during the early COVID-19 pandemic to characterize the impact of the pandemic on surveillance methods. METHODS A scoping search was conducted in multiple databases and by scanning key government and public health organization websites from March 2020 to January 2022. Published papers and gray literature that described the application of new or revised approaches to public health surveillance were included. Papers that discussed the implications of novel public health surveillance approaches from ethical, legal, security, and equity perspectives were also included. The surveillance subject, method, location, and setting were extracted from each paper to identify trends in surveillance practices. Two public health epidemiologists were invited to provide their perspectives as peer reviewers. RESULTS Of the 14,238 unique papers, a total of 241 papers describing novel surveillance methods and changes to surveillance methods are included. Eighty papers were review papers and 161 were single studies. Overall, the literature heavily featured papers detailing surveillance of COVID-19 transmission (n=187). Surveillance of other infectious diseases was also described, including other pathogens (n=12). Other public health topics included vaccines (n=9), mental health (n=11), substance use (n=4), healthy nutrition (n=1), maternal and child health (n=3), antimicrobial resistance (n=2), and misinformation (n=6). The literature was dominated by applications of digital surveillance, for example, by using big data through mobility tracking and infodemiology (n=163). Wastewater surveillance was also heavily represented (n=48). Other papers described adaptations to programs or methods that existed prior to the COVID-19 pandemic (n=9). The scoping search also found 109 papers that discuss the ethical, legal, security, and equity implications of emerging surveillance methods. The peer reviewer public health epidemiologists noted that additional changes likely exist, beyond what has been reported and available for evidence syntheses. CONCLUSIONS The COVID-19 pandemic accelerated advancements in surveillance and the adoption of new technologies, especially for digital and wastewater surveillance methods. Given the investments in these systems, further applications for public health surveillance are likely. The literature for surveillance methods was dominated by surveillance of infectious diseases, particularly COVID-19. A substantial amount of literature on the ethical, legal, security, and equity implications of these emerging surveillance methods also points to a need for cautious consideration of potential harm.
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Effectiveness and Feasibility of Telehealth-Based Dietary Interventions Targeting Cardiovascular Disease Risk Factors: Systematic Review and Meta-Analysis.
Trivedi, R, Elshafie, S, Tackett, R, Young, H, Sattler, ELP
Journal of medical Internet research. 2024;:e49178
Abstract
BACKGROUND Telehealth-based dietary interventions were recommended for cardiovascular disease (CVD) management during the COVID-19 pandemic; however, data regarding their effectiveness and feasibility are limited. OBJECTIVE We aimed to examine (1) the effectiveness of telehealth-based dietary interventions in improving clinical CVD risk factors and (2) the feasibility of these interventions among individuals with CVD. METHODS To conduct this systematic review and meta-analysis of randomized controlled trials (RCTs), 2 investigators searched PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov databases based on predetermined search terms and included English-language RCTs published between January 2000 and July 2022. The Cochrane Risk of Bias tool was used to assess RCT quality. To evaluate intervention effectiveness, weight, BMI, systolic and diastolic blood pressure, and levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, or blood glucose were compared postintervention in telehealth and usual care (UC) groups. Feasibility was determined through the number of participants retained in intervention and UC groups. Pooled data for each CVD outcome were analyzed using a random effects model. Mean difference (MD), standardized MD, or risk ratio were calculated using R software. RESULTS A total of 13 RCTs with 3013 participants were included in the analysis to assess the effectiveness and feasibility of telehealth-based dietary interventions among individuals with CVD. Participants had a mean age of 61.0 (SD 3.7) years, and 18.5% (n=559) were women. Approximately one-third of RCTs were conducted in the United States (n=4, 31%). Included studies used telephone, app, text, audio-visual media, or website-based interventions. Of the 13 included studies, 3 were of high quality, 9 were of moderate quality, and only 1 was of low quality. Pooled estimates showed systolic blood pressure (MD -2.74, 95% CI -4.93 to -0.56) and low-density lipoprotein cholesterol (standardized MD -0.11, 95% CI -0.19 to -0.03) to be significantly improved among individuals with CVD as a result of telehealth-based dietary interventions compared to UC. No significant difference in effectiveness was detected for weight, BMI, and levels of diastolic blood pressure, total cholesterol, high-density lipoprotein, and triglycerides between telehealth-based dietary interventions and UC among those with CVD. There was no significant difference between the feasibility of telehealth-based dietary interventions versus UC. Significant I2 indicated moderate to considerable heterogeneity. CONCLUSIONS Telehealth-based dietary interventions show promise in addressing CVD risk factors.