Association of genetic polymorphisms in glucocorticoid pathway with dexamethasone treatment in COVID-19 patients

Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.

Diazepam and exercise training combination synergistically reduces lipopolysaccharide-induced anxiety-like behavior and oxidative stress in the prefrontal cortex of mice.

Anxiety-related disorders are among the most important risks for global health, especially in recent years due to the COVID-19 pandemic. Benzodiazepines like diazepam are generally used to treat anxiety disorders, but the overall outcome is not always satisfactory. This is why psychiatrists encourage patients with anxiety to change their lifestyle habits to decrease the risk of anxiety recurrence. However, the effect of diazepam and exercise in combination is unknown. This study aimed to investigate the effect of diazepam alone or in combination with swimming exercise on lipopolysaccharide (LPS)-induced anxiety-like behavior and oxidative stress in the hippocampus and prefrontal cortex of mice. Mice were exposed to diazepam and swimming exercise alone or in combination with each other and then received LPS. We assessed anxiety-like behavior using open field and light-dark box and measured oxidative markers including glutathione (GSH), malondialdehyde (MDA), and glutathione disulfide (GSSG) in the hippocampus and prefrontal cortex. The findings showed that LPS increased anxiety-related symptoms and oxidative stress by decreasing GSH and increasing MDA and GSSG levels in the prefrontal cortex but not in the hippocampus. Although diazepam alone did not reduce anxiety-like behavior and oxidative stress, it in combination with exercise significantly decreased anxiety-like behavior and oxidative stress in the prefrontal cortex of LPS-treated mice. This drug and exercise combination also displayed a more effective effect in comparison with exercise alone. Overall, this study suggests that diazepam in combination with swimming exercise has higher efficacy on anxiety-like behavior and oxidative stress than when they are used alone.

Association of deletion polymorphisms of GSTM1 and GSTT1 genes with the degree of lung damage in elderly people after COVID-19

To analyze the association of polymorphisms of the GSTM1 and GSTT1 genes with the degree of lung damage in elderly people in Yakutia who suffered from COVID-19, a survey of volunteers who had a coronavirus infection aged 60 to 75 years (average age 64.470 +/- 0.602 years) was conducted. The results of our study find out that the combination of zero deletion genotypes GSTM1 and GSTT1 is a risk factor for the development of severe lung lesions in the elderly.

Ferroptosis Is a Potential Therapeutic Target for Pulmonary Infectious Diseases

Ferroptosis is a new type of iron-dependent cell death caused by lipid peroxide (LPO) accumulation and involved in disease of pulmonary infection. The dysregulation of iron metabolism, the accumulation of LPO, and the inactivation and consumption of glutathione peroxidase 4 (GPX4) are the crucial cause of ferroptosis. Pulmonary infectious diseases caused by Pseudomonas aeruginosa (PA), Mycobacterium tuberculosis (MTB), and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are associated with ferroptosis. Ferroptosis may be a potential therapeutic target for pulmonary infectious diseases. However, the mechanisms by which these infections are involved in ferroptosis and whether pulmonary infectious diseases caused by Staphylococcus aureus, Klebsiella pneumoniae, and Leishmania spp are related to ferroptosis are unclear. Accordingly, more researches are needed.Copyright © 2023 Yurong Zhang et al.

Lung injury associated with an e-cigarette (vaping) use during the COVID-19 pandemic

In recent years, the excessive use of electronic cigarettes (e-cigarettes), and vaping, as a re-placement for traditional tobacco cigarettes, have highlighted potential health risks for users. One such risk is the development of "electronic cigarette (vaping) product use-associated lung injury" (EVALI). This type of lung injury has an unclear cause that may be related to the various components found in e-cigarette fluids. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (coronavirus disease . 2019 or COVID-19) may worsen EVALI symptoms in individuals with both conditions. This could be due to the increased oxidative stress and inflammation caused by e-cigarette use, as re-search shows increased levels of reactive oxygen species (ROS) and decreased glutathione. In this paper, we present two critical cases of COVID-19 patients with a history of chronic e-cigarette smoking and describe their clinical progression during hospitalization. The findings suggest that their prolonged use of e-cigarettes may have sig-nificantly impacted the severity of the disease.Copyright © 2023, The Indonesian Foundation of Critical Care Medicine. All rights reserved.

Immunogenetic studies on SARS-CoV-2: Our experience at SKIMS

Background: The pathophysiology of viral-infections is highly complex and involves host immunocompetence, host genetics, and gene-environment interactions. We hypothesized that polymorphic variants in host genes, blood group and previous vaccination status against H1N1 may affect the clinical course of covid-19 infection. Method(s): A total of 202 subjects who were RT-PCR negative after Covid-19 infection were recruited. We investigated association between Covid-19 infection (Severity and recovery period) and multiple factors including ABO and Rh blood groups, H1N1 vaccination, polymorphism in Viral susceptibility genes (ACE2 G8790A), and polymorphism in host response genes (ACE I/D rs4646994, IL6- 174G/C, GSTT1/GSTM1 I/D and GSTP1 Ile 105 Val). Result(s): B-ve and O-ve ABO and Rh blood groups had significantly higher Covid-19 recovery period applied on one-vs.-all in a nonparametric t-test (p<0.05). Subjects who had vaccinated themselves against H1N1 presented with a lower recovery-period (p<0.05). Both variables (blood group and H1N1 vaccination) were not however associated with Covid-19 severity. Out of the studied polymorphisms, ACE2 G8790A and GSTT1/GSTM1 were significantly associated with covid-19 infection. Our results indicated that G/G genotype of ACE2 G8790A (OR 3.52, P 0.007) and GSTT1/ GSTM1 null (M1 - / - OR = 3.98, P = 0.0004;T1 - / - OR 3.84, P = 0.004) and double null (M1 - / - /T1 - / - OR = 9.66, P = 0.001) are likely to be associated with an increased risk for severe-critical outcomes in individuals with COVID-19. Other polymorphisms analyzed in this study were found to have no significant association with Covid-19 outcome. Conclusion(s): This study suggests that outcome of Covid-19 infection is affected by both clinical and genetic factors. Thus it seems plausible to utilize these factors as prediction and susceptibility markers in the prognosis of COVID-19, which may help to personalize the treatment.

Interaction Between the Viral RNA Leader Sequence and nsp1 in SARS Coronavirus

Nonstructural protein 1 (nsp1) of severe acute respiratory syndrome coronavirus (SARS-CoV), inhibits host translation thorough cleaving host mRNA and blocking the translation initiation site on the 40S ribosome. Stem-Loop-1 (SL-1) of the viral RNA leader sequence has been identified to bind to nsp1, allowing viral RNA to escape translation repression. However, the specific residues on nsp1 and the specific sequences on SL-1 important to binding have not been experimentally verified. To investigate this binding, we used gel-shift assay and RNA pull-down to verify binding between nsp1 and SL-1. By mutating SL- 1, we seek to identify the nucleotides of SL-1 that bind to nsp1. Based on recent literature, we hypothesized that disrupting the stem region of SL-1 will decrease binding between nsp1 and SL-1. Moreover, we seek to identify the residues important to binding to SL-1 by mutating specific amino acids of nsp1. Interestingly, nsp1 is a small protein (180 amino acids) with intrinsically unstructured regions at both C- and N-terminal ends of the protein. Based on recent literature we hypothesize that disrupting the R124 and K125 residues will decrease binding to SL-1. The results of this study will increase the knowledge of how viral RNA is able to escape suppression of host gene expression. To investigate the binding of nsp1 to SL1, we used nsp1 purified from bacterial lysate using glutathione beads followed by precision protease cleavage of GST-nsp1, and biotinylated RNA. LightShift Chemiluminescence RNA EMSA Kit (Promega) was used to detect the RNA in complex with nsp1 using a gel shift assay. Contrary to our hypothesis, we found an increase in nsp1 binding to the RNA carrying stem mutation, and a decrease in nsp1 binding to the RNA with the loop mutation. Moreover, we observed two distinct bands in the stem mutant indicating two possible binding sites on SL-1. Using an electrophoretic mobility shift assay, the loop region of SL-1 has been determined to be vital for binding to nsp1 in vitro. We hypothesize when the stem was mutated, we created a new binding site for nsp1. Currently we are further investigating several mutations in SL-1 to identify the actual binding site. This project was supported by the DRP award from SC INBRE (NIGMS, P20GM103499).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Association between vitamin D3 and glutathione levels in COVID-19 individuals

Background: COVID-19 is an infectious disease associated with high rates of infection and death, espe-cially in older males with low glutathione (GSH) and vitamin D (vit D) levels. The GSH status is positively associated with bioavailability of vit D. GSH deficiency correlated with increased oxidative stress (OxS) and inflammatory markers, which implicate an increase in the severity of the disease. Objective: To verify the interaction of vit D and GSH levels among healthy individuals and COVID-19 patients. Method: The study population involved 166 healthy individuals, who formed the control group, and 171 COVID-19 patients. OxS and antioxidant parameters, and levels of vit D and inflammatory markers were estimated in both groups. Results: The COVID-19 patients showed significantly higher levels for malondialdehyde (MDA), protein carbonyl group (PC), interleukin-6, tumor necrosis factor alpha, and C-reactive protein and significantly low levels for GSH and vit D compared to the healthy control group. The aged and male COVID-19 groups displayed significantly higher levels of MDA and PC and significantly low levels of GSH compared with the younger and women groups. Conclusion: The COVID-19 patients displayed higher levels of OxS and inflammatory markers and low levels of antioxidant GSH and vit D, which developed by advancement of age especially within males.

Association between vitamin D3 and glutathione levels in COVID-19 individual

Background: COVID-19 is an infectious disease associated with a high rate of infection and death, especially for the older males when they have low levels of glutathione (GSH) and vitamin D. The GSH status is positively associated with the bioavailability of vitamin D. The GSH deficiency is correlated by increased oxidative stress and inflammatory markers which implicate the increase in the severity of the disease. Objective: To verify the vitamin D-GSH levels interaction among healthy and COVID- 19 patients. Method: Control healthy group (166) individuals and (171) COVID-19 patients were involved in this study. Oxidative stress and antioxidant parameters, vitamin D, and inflammatory markers were estimated in both Results: The COVID-19 patients showed significantly higher levels of malondialdehyde (MDA), protein and significantly low levels of GSH and vitamin D compared to the healthy control group, the aged and male COVID-19 group display significantly higher levels of MDA, PC, and significantly low levels for GSH Conclusion: The COVID-19 patient correlated with higher oxidative stress, inflammatory marker, and low level of antioxidant GSH and vitamin D which occur with advancing age, especially within the male.

The possibilities of using the effects of ozone therapy in neurology

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHOD(S): The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULT(S): Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION(S): Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.Copyright © 2021 Neuroendocrinology Letters.

The Multifaceted Role of Glutathione S-Transferases in Health and Disease.

In humans, the cytosolic glutathione S-transferase (GST) family of proteins is encoded by 16 genes presented in seven different classes. GSTs exhibit remarkable structural similarity with some overlapping functionalities. As a primary function, GSTs play a putative role in Phase II metabolism by protecting living cells against a wide variety of toxic molecules by conjugating them with the tripeptide glutathione. This conjugation reaction is extended to forming redox sensitive post-translational modifications on proteins: S-glutathionylation. Apart from these catalytic functions, specific GSTs are involved in the regulation of stress-induced signaling pathways that govern cell proliferation and apoptosis. Recently, studies on the effects of GST genetic polymorphisms on COVID-19 disease development revealed that the individuals with higher numbers of risk-associated genotypes showed higher risk of COVID-19 prevalence and severity. Furthermore, overexpression of GSTs in many tumors is frequently associated with drug resistance phenotypes. These functional properties make these proteins promising targets for therapeutics, and a number of GST inhibitors have progressed in clinical trials for the treatment of cancer and other diseases.

Prolonged stay and endothelial dysfunction in hospitalized patients with covid-19

Introduction: COVID-19 is not only a respiratory disease, produces a severe systemic and multi-organ response. This illness generates vascular disorders, leading the patient to endothelial dysfunction. It acutely and chronically affects the patient's evolution, prolonging the patient's stay and worsening life prognosis. Objective(s): To evaluate differences in endothelial dysfunction present in patients hospitalized for COVID-19 who had a hospital stay longer than 18 days compared to those who did not. Method(s): A prospective cohort study was conducted. Hospitalized patients with confirmed SARS-COV 2 andolder than 18 years were included. Subjects in whom endothelial function markers could not be processed wereexcluded. Endothelial dysfunction was evaluated using E-selectin, endothelin-1, glutathione-s-transferase, arginase, and MDAM. A prolonged hospital stay was established >=18 days. Result(s): A total of 165 patients were evaluated, the average age of the population was 57.18 +/- 13.37 years, 73.33% were men. Subjects with prolonged hospital stay were older (59.38 +/- 12.08 vs 51.15 +/- 14.96, p=0.004), a higher number of patients required intubation (87.60 % vs 75, p=0.049) and e-selectin (1 [0.79 - 1.32] vs 0.88 [0.68 -1.14], p=0.0323) compared to subjects without prolonged hospital stay. Conclusion(s): Hospitalized patients over 18 days showed elevated levels of E-selectin reflecting endothelial damage, affecting vascular homeostasis, added to this, a significant number of them were intubated, increasing the risk of mortality, as well as future cardiovascular complications.

Role of oxidative stress and therapeutic options in SARS-COV-2 infection [Version 1, Peer Review - In Progress]

Introduction: elevated levels of oxidative stress in patients with SARS-CoV-2 infection generate tissue damage, causing organ dysfunction and generating a suitable environment for viral replication. Aim: to describe the mechanisms by which oxidative stress is generated in patients with Sars-Cov-2 and its therapeutic options. Methodology: a non-experimental and narrative study of bibliographic review type was carried out, data will be collected from original articles in indexed journals using the PubMed database. Results: patients with SARS-CoV-2 infection present elevated levels of oxidative stress, on the contrary, the levels of antioxidant agents are depleted, increasing the degree of oxidative stress to a greater extent. The use of N-acetylcysteine in a COVID-19 positive patient is a subject under discussion since, although there are inconsistencies in its degree of efficacy, no adverse effects of any kind have been observed. Conclusions: there are antioxidant therapeutic options under study, however, despite having a high safety profile, their efficacy in the treatment of COVID-19 is still unproven. © Este es un artículo en acceso abierto, distribuido bajo los términos de una licencia Creative Commons.

Role of vitamin D, folic acid, ferritin, inflammation and oxidative stress in the pathogenesis of COVID-19

The COVID-19 pandemic is one of the most devastating and significant events of recent times. COVID-19 has so far become one of the worst infectious disease outbreaks of recent times, with more than 635 million cases and more than 6.6 million deaths. Viruses cause an explosion of inflammatory cytokines and reactive oxygen types. Oxidative stress is thought to have a key role in COVID-19. vitamin D, folic acid, calcium (Ca), magnesium (Mg) and ferritin levels are thought to be associated with COVID-19. This study aims to investigate the role of oxidative stress, inflammation, vitamin D and folic acid, ferritin, Ca and Mg in the pathogenesis of COVID-19. Material(s) and Method(s): 45 patients diagnosed with COVID-19 and 45 healthy persons (control group) were included in the study. Vitamin D, ferritin, folic acid, CRP, Ca, Mg and Phosphorus were measured in an autoanalyzer, and SOD, GSH-Px and MDA were spectrophotometrically measured in the serum of the participants. TNF-alpha, IL-1beta and IL6 levels were studied by the ELISA method. Result(s): The activity of SOD, GSH-px, antioxidant enzymes, Serum vitamin D, folic acid, Ca and Mg of the COVID-19 group was found to be significantly lower than the control group (p<0.05). Conclusion(s): Again, the levels of MDA, TNF-alpha, IL-1beta, IL-6, CRP and ferritin in the Covid-19 group were found to be significantly higher than in the control group (p<0.05).Antioxidant enzyme activities were low and oxidative stress was high in patients with COVID-19. At the same time, the levels of serum ferritin, CRP, TNF-alpha, IL-1beta and IL6 were high, and levels of Ca and Mg were low in patients with COVID-19.According to these results, we hypothesize think that the level of oxidative stress, inflammation, vitamin D, and serum ferritin, Ca, and Mg levels play a role in the pathogenesis of COVID-19. Future clinical trials should be conducted to further clarify the pathogenesis in patients with COVID-19.Copyright © 2022 Mattioli 1885. All rights reserved.

The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review.

Immunothrombosis has emerged as a dominant pathological process exacerbating morbidity and mortality in acute- and long-COVID-19 infections. The hypercoagulable state is due in part to immune system dysregulation, inflammation and endothelial cell damage, as well as a reduction in defense systems. One defense mechanism in particular is glutathione (GSH), a ubiquitously found antioxidant. Evidence suggests that reduction in GSH increases viral replication, pro-inflammatory cytokine release, and thrombosis, as well as decreases macrophage-mediated fibrin removal. The collection of adverse effects as a result of GSH depletion in states like COVID-19 suggest that GSH depletion is a dominant mechanism of immunothrombosis cascade. We aim to review the current literature on the influence of GSH on COVID-19 immunothrombosis pathogenesis, as well as the beneficial effects of GSH as a novel therapeutic for acute- and long-COVID-19.

SARS-CoV-2 Main Protease Targets Host Selenoproteins and Glutathione Biosynthesis for Knockdown via Proteolysis, Potentially Disrupting the Thioredoxin and Glutaredoxin Redox Cycles.

Associations between dietary selenium status and the clinical outcome of many viral infections, including SARS-CoV-2, are well established. Multiple independent studies have documented a significant inverse correlation between selenium status and the incidence and mortality of COVID-19. At the molecular level, SARS-CoV-2 infection has been shown to decrease the expression of certain selenoproteins, both in vitro and in COVID-19 patients. Using computational methods, our group previously identified a set of six host proteins that contain potential SARS-CoV-2 main protease (Mpro) cleavage sites. Here we show experimentally that Mpro can cleave four of the six predicted target sites, including those from three selenoproteins: thioredoxin reductase 1 (TXNRD1), selenoprotein F, and selenoprotein P, as well as the rate-limiting enzyme in glutathione synthesis, glutamate-cysteine ligase catalytic subunit (GCLC). Cleavage was assessed by incubating recombinant SARS-CoV-2 Mpro with synthetic peptides spanning the proposed cleavage sites, and analyzing the products via UPLC-MS. Furthermore, upon incubation of a recombinant Sec498Ser mutant of the full TXNRD1 protein with SARS-CoV-2 Mpro, the predicted cleavage was observed, destroying the TXNRD1 C-terminal redox center. Mechanistically, proteolytic knockdown of both TXNRD1 and GCLC is consistent with a viral strategy to inhibit DNA synthesis, conserving the pool of ribonucleotides for increased virion production. Viral infectivity could also be enhanced by GCLC knockdown, given the ability of glutathione to disrupt the structure of the viral spike protein via disulfide bond reduction. These findings shed new light on the importance of dietary factors like selenium and glutathione in COVID-19 prevention and treatment.

The role of high dose vitamin d and glutathione supplementation in COVID-19 treatment: A case series.

COVID-19 has been affecting millions of people worldwide and becoming a global public health burden. Therefore, exploring treatment options is essential to help flatten the curve and reduce hospitalization time. This is a case series of ten COVID-19 patients in Jakarta and Tangerang, Indonesia, who received a high dose of vitamin D and glutathione supplementation daily. Within 5-7 days of treatment, all patients were confirmed COVID-19 negative. To date, this is the first report from Indonesia describing the potential benefit of supplementing vitamin D and glutathione concurrently in improving clinical conditions and expediting the recovery time of COVID-19 patients.

Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections.

The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.

Salat dhuha effect on oxidative stress in elderly women: A randomized controlled trial.

Background: The aging process and a chronic sedentary lifestyle in the elderly as a result of physical restrictions during the COVID-19 pandemic, induces oxidative stress through oxygen supply and antioxidant activity imbalance which in turn induce degenerative diseases. Salat dhuha as a prayer and mind-body medicine which is practiced by the Muslim community can hopefully be a solution to decrease oxidative stress in the elderly. Objective: To evaluate the acute physiological effects of salat dhuha on Glutathione Peroxidase activity (GPx) as an antioxidant and Malondialdehyde (MDA) as an oxidant in healthy elderly Muslim women population who have done salat dhuha regularly. Method: A randomized controlled study was done on elderly women (aged 60-74 years old) who are treated in the North Sumatra Government's Nursing Home in Binjai and who routinely do 2 rakaat of salat dhuha every day. Several physical, clinical, and blood examinations were done pre and post-intervention. 101 elderly Muslim women in the nursing home were selected, 26 met the study criteria and were included in the study. The volunteers were randomized into 2 groups using lottery papers, the "2-rakaat salat dhuha group" (n = 13) and the "8-rakaat salat dhuha group" (n = 13). All volunteers did salat dhuha for at least 5 days per week for 6 weeks. Result: 24 elderly women completed the study, and one volunteer from each group dropped out. The characteristics of participants from both groups were homogenous. Results of the t-independent analysis showed that MDA concentrations in both groups in the pre and post-test were not significantly different (p > 0,05). Mann Whitney analysis showed that GPx on both groups in the pre and post-test were not significantly different (p > 0,05). Paired sample t-test analysis on the MDA concentrations pre and post-test in the 8-rakaat group showed a significant difference in MDA levels (p < 0,05). The 8-rakaat salat dhuha group showed that GPx activity increases as much as 8,9% and MDA levels decrease as much as 48,35 % after 6 weeks. Conclusion: Salat dhuha promotes redox homeostasis and has the potential to prevent oxidative stress in elderly women.

Nutritional deficiencies that may predispose to long COVID.

Multiple nutritional deficiencies (MND) confound studies designed to assess the role of a single nutrient in contributing to the initiation and progression of disease states. Despite the perception of many healthcare practitioners, up to 25% of Americans are deficient in five-or-more essential nutrients. Stress associated with the COVID-19 pandemic further increases the prevalence of deficiency states. Viral infections compete for crucial nutrients with immune cells. Viral replication and proliferation of immunocompetent cells critical to the host response require these essential nutrients, including zinc. Clinical studies have linked levels of more than 22 different dietary components to the likelihood of COVID-19 infection and the severity of the disease. People at higher risk of infection due to MND are also more likely to have long-term sequelae, known as Long COVID.