Prevention and Treatment of Acute Respiratory Distress Syndrome by COVID-19: Role of Vitamin D on Immunomodulation and Renin-Angiotensin-Aldosterone System Regulation

The leading cause of complications or death from COVID-19 is due to the development of acute respiratory distress syndrome (ARDS). This syndrome is characterized by exacerbated inflammation, mainly at the pulmonary level, and an over-activation of the renin-angiotensin-aldosterone system (RAAS), usually culminating in death or permanent respiratory sequelae in the SARS-CoV-2 infected patients. In this sense, it has been proposed that vitamin D exerts numerous immunomodulatory effects by acting on various types of immune and epithelial cells, as well as being able to stimulate the protective arm (ACE2/Ang-(1-7)) and inhibit the harmful arm (ACE/Ang-II) of the RAAS. Therefore, some of the main mechanisms underlying these effects mediated by vitamin D and its receptors are discussed in the present review. The analysis of these mechanisms would positively influence the prevention and treatment of ARDS, thus preventing the progression of the disease and improving the prognosis of the patients.Fil: Carmona, Maximiliano. Gobierno de la Provincia de Mendoza. Hospital Luis Lagomaggiore.; Argentina. Ministerio de Salud de la Nación; Argentina. Ministerio de Desarrollo Social; Argentina. Ministerio de Desarrollo Social. Secretaria de Deportes de la Nacion; ArgentinaFil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentin

Relationship Between Vitamin D Levels and Covid-19 Severity Due to Circulating SARS-COV-2 Variants in Argentina: A Presentation of Clinical Cases

There is growing evidence that serum vitamin D levels are inversely related to the severity of COVID-19. However, it is not yet known whether this relationship is observed independently of the type of variant of SARS-CoV-2 that has caused the infection or if this is variant-dependent. In this context, we studied a series of clinical cases with a positive diagnosis of COVID-19 and required hospitalization in the unit of critical care at a hospital from Argentina. At the time of this study, the variants of SARS-CoV-2 with the highest circulation in this country were the Lambda (Andina) and Gamma (Manaus) variants. The obtained results would indicate that the inverse relationship studied is evidenced, at least, against infection by the two variants mentioned. However, to deepen this possible relationship against other variants, additional studies should be carried out in populations with a different viral circulation profile.Fil: Carmona, Maximiliano. Ministerio de Salud de la Nación; Argentina. Ministerio de Desarrollo Social; Argentina. Ministerio de Desarrollo Social. Secretaria de Deportes de la Nacion; Argentina. Gobierno de la Provincia de Mendoza. Hospital Luis Lagomaggiore.; ArgentinaFil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentin

Differences in RAAS/vitamin D linked to genetics and socioeconomic factors could explain the higher mortality rate in African Americans with COVID-19

COVID-19 is said to be a pandemic that does not distinguish between skin color or ethnic origin. However, data in many parts of the world, especially in the United States, begin to show that there is a sector of society suffering a more significant impact from this pandemic. The Black population is more vulnerable than the White population to infection and death by COVID-19, with hypertension and diabetes mellitus as probable predisposing factors. Over time, multiple disparities have been observed between the health of Black and White populations, associated mainly with socioeconomic inequalities. However, some mechanisms and pathophysiological susceptibilities begin to be elucidated that are related directly to the higher prevalence of multiple diseases in the Black population, including infection and death by COVID-19. Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system (RAAS) in Black people differ considerably from those of other races. The role of these factors in the development and progression of hypertension and multiple lung diseases, among them SARS-CoV-2 infection, is well established. In this sense, the present review attempts to elucidate the link between vitamin D and RAAS ethnic disparities and susceptibility to infection and death by COVID-19 in Black people, and suggests possible mechanisms for this susceptibility.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Ferder, León. Universidad de Maimónides; ArgentinaFil: Inserra, Felipe. Universidad de Maimónides; ArgentinaFil: García, Joxel. No especifíca;Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Vitamin D deficiency in African Americans is associated with a high risk of severe disease and mortality by SARS-CoV-2

COVID-19 is said to be a pandemic that does not distinguish skin color or ethnic origin, but data in many parts of the world, especially in the United States, begins to show that there is a sector of society that is suffering a more significant impact from this pandemic. The black population is being more vulnerable than the white population to infection and death by COVID-19, and hypertension and diabetes mellitus seems to predispose to this vulnerability. Over time, multiple disparities have been observed between the health of blacks and whites, mainly associated with inequalities in the socio-economic scope. However, little by little, some mechanisms and pathophysiological susceptibilities that are directly related to the higher prevalence of multiple diseases in the black population, including infection and death by COVID-19, begin to be elucidated.Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system in black people are considerably different between this and other races, and it is well established their role in the development and progression of hypertension and multiple lung diseases, among them, COVID-19 infection.This letter to discuss and proposes whether or not vitamin D and renin-angiotensin-aldosterone system ethnical disparities influence susceptibility to infection and death by COVID-19 in black people and suggests possible mechanisms for this susceptibility.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Felipe. Universidad Maimónides; ArgentinaFil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: García, Joxel. Ambitious Solutions for Health Cures; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

We are not alone: Melatonin and vitamin d may be good company during covid-19 pandemic

Loneliness and social isolation are associated with depression, anxiety and a progressive loss of higher cognitive faculties, mainly in older adults. In the current pandemic situation, with serious restrictions that limit interactions with members of our social circles, these cognitive alterations are becoming progressively more obvious in young adults, adolescents and even children. With the addition of eating disorders, sleep disturbances, and lack of exposure to solar radiation due to confinement, the condition can be considerably worse. Fortunately, there are two allies which from a psychological point of view, have many common features and could help to reverse some of the effects of social isolation; these molecules are melatonin and vitamin D. Their complementary functions on circadian rhythmicity may be useful in reestablishing mood balance. Thus, we suggest a re-education in new hygienic-dietary habits, especially related to the maintenance of adequate levels of melatonin and vitamin D, which may help prevent and possibly reverse the cognitive and psychological disorders until social contact is reestablished.Fil: García Menéndez, Sebastián Marcelo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; ArgentinaFil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reiter, Russel. University of Texas Health Science Center at Houston; Estados UnidosFil: Manucha, Walter Ariel Fernando. Universidad del Aconcagua. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

New proposal involving nanoformulated melatonin targeted to the mitochondria as a potential COVID-19 treatment

Melatonin may be a powerful auxiliary therapy in the prevention and treatment of viral infections, such as coronavirus disease 2019 (COVID-19). Casually, the so-called ‘super immunity’ of bats and the usually high levels of melatonin in children could contribute to their high resistance to the SARS-CoV-2 virus. Melatonin seems to play a key role in suppressing COVID-19 infections. This endogenous antioxidant inhibits cell apoptosis, blocks the inflammasomes that mediate lung inflammation, reduces blood vessel permeability which limits alveolar edema, improves anxiety and sleeps habits that stimulate general immunity and prevents lung fibrosis. These complications, which are usually the main consequences of COVID-19, may be significantly attenuated by melatonin...Fil: Martín Giménez, Virna Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Católica de Cuyo. Facultad de Ciencias Químicas y Tecnológicas; ArgentinaFil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; ArgentinaFil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; ArgentinaFil: Reiter, Russel. University of Texas at San Antonio; Estados Unido

Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D

Due to its high degree of contagiousness and like almost no other virus, SARS-CoV-2 has put the health of the world population on alert. COVID-19 can provoke an acute inflammatory process and uncontrolled oxidative stress, which predisposes one to respiratory syndrome, and in the worst case, death. Recent evidence suggests the mechanistic role of mitochondria and vitamin D in the development of COVID-19. Indeed, mitochondrial dynamics contribute to the maintenance of cellular homeostasis, and its uncoupling involves pathological situations. SARS-CoV-2 infection is associated with altered mitochondrial dynamics with consequent oxidative stress, pro-inflammatory state, cytokine production, and cell death. Furthermore, vitamin D deficiency seems to be associated with increased COVID-19 risk. In contrast, vitamin D can normalize mitochondrial dynamics, which would improve oxidative stress, pro-inflammatory state, and cytokine production. Furthermore, vitamin D reduces renin–angiotensin–aldosterone system activation and, consequently, decreases ROS generation and improves the prognosis of SARS-CoV-2 infection. Thus, the purpose of this review is to deepen the knowledge about the role of mitochondria and vitamin D directly involved in the regulation of oxidative stress and the inflammatory state in SARS-CoV-2 infection. As future prospects, evidence suggests enhancing the vitamin D levels of the world population, especially of those individuals with additional risk factors that predispose to the lethal consequences of SARS-CoV-2 infection.Fil: de Las Heras, Natalia. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; EspañaFil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo. Facultad de Ciencias Quimicas y Tecnologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Ferder, León. Universidad Maimónides; ArgentinaFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Lahera Juliá, Vicente. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; Españ

Genomic or Non-Genomic? A Question about the Pleiotropic Roles of Vitamin D in Inflammatory-Based Diseases

Vitamin D (vit D) is widely known for its role in calcium metabolism and its importance for the bone system. However, various studies have revealed a myriad of extra-skeletal functions, including cell differentiation and proliferation, antibacterial, antioxidant, immunomodulatory, and anti-inflammatory properties in various cells and tissues. Vit D mediates its function via regulation of gene expression by binding to its receptor (VDR) which is expressed in almost all cells within the body. This review summarizes the pleiotropic effects of vit D, emphasizing its anti-inflammatory effect on different organ systems. It also provides a comprehensive overview of the genetic and epigenetic effects of vit D and VDR on the expression of genes pertaining to immunity and anti-inflammation. We speculate that in the context of inflammation, vit D and its receptor VDR might fulfill their roles as gene regulators through not only direct gene regulation but also through epigenetic mechanisms

COVID-19 pandemic and vitamin D deficiency: a different approach with an analysis of the findings and a complimentary proposal

Vitamin D is an essential immune-modulator with receptors widely distributed throughout the body, and its serum levels fluctuate significantly among individuals between winter and summer months (from 30 to 50%). This study examines the association between low vitamin D status and prevalence of COVID-19 cases around the world and proposes a relationship between the seasonal character of the human immune system strength rather than to the seasonal infectivity of viruses. Also, this review suggests the observed geographical disparities in COVID-19 infections were due to differences in vitamin D levels. On the international scale, serum vitamin D levels are reportedly lowest in China, the Middle East, and South Europe; these populations also had the largest outbreaks of COVID-19 cases. In addition to the geographical differences in vitamin D status, there are known risk groups (ethnic, age-related, pregnancies). On the contrary, some countries including Canada, Finland, and North Europe incorporate increased amounts of vitamin D through fortified foods, vitamin D supplements, and sunbathing. These countries show the lowest morbidity and mortality rates by COVID-19 infection and demonstrate that lower ambient temperatures do not contribute to a higher number of COVID-19 cases. COVID-19 has spread around the globe almost simultaneously in both warm and cold areas. Given this information, vitamin D measurement should become an essential component of public health monitoring as a biomarker of immunity status. Clinical trials should be conducted to confirm this hypothesis. COVID-19 tests should be performed together with vitamin D status tests to verify this proposed relationship.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo. Facultad de Ciencias Quimicas y Tecnologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergam, Ivana. Croatia Osiguranje Pension Company; CroaciaFil: Inserra, Felipe. Universidad Maimónides; ArgentinaFil: Ferder, Leon Fernando. Universidad Maimónides; ArgentinaFil: Reiter, Russel. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentin

Key Aspects to Consider about Beneficial and Harmful Effects on the Central Nervous System by the Endocannabinoid Modulation Linked to New Cardiovascular Therapies

The endocannabinoid system (ECS) is closely related to the central nervous system (CNS) and exerts a promising therapeutic potential on the cardiovascular system, mainly through its neuromodulatory, neuroprotective, and neuroinflammatory effects. For this reason, when designing new treatments for different cardiovascular pathologies, it is necessary to consider the side effects that such therapies can cause at the neurological level. ObjectiveTo deepens the knowledge of each cannabinoid (CB) and the molecular mechanisms that can lead to undesired results to analyze its possible use in cardiovascular therapy.MethodsThe present review analyzes the psychoactive consequences of anandamide and other similar substances such as other endocannabinoids, phytocannabinoids, and synthetic cannabinoids, to assess their little-explored therapeutic potential in clinical investigations. Finally, the major behavioral tests most used until the moment to predict possible changes in the conduct of animals treated with various substances of cannabinoid nature are summarized. It has been observed that endocannabinoids have few adverse central nervous effects, unlike the phytocannabinoids, synthetic cannabinoids and antagonists of CB receptors. These molecules act on typical receptors due to a similar spatial configuration; however, their structure is not identical between them. For this reason, the competition and displacement of endogenous ligands of the ECS by exogenous cannabinoids provokes an alteration in the CNS normal functioning, leading to the associated side effects. An exhaustive analysis of each cannabinoid and the molecular mechanisms that can lead to undesired results is necessary at the time of proposing them as news cardiovascular therapeutic alternatives.Fil: Martín Giménez, Virna Margarita. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Mocayar Maron, Feres Jose. Universidad Nacional de Cuyo.Facultad de Ciencias Médicas; ArgentinaFil: Kassuha, Diego Enrique. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: Ferder, Leon Fernando. Universidad de Miami; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentin