Could Selenium Supplementation Prevent COVID-19? A Comprehensive Review of Available Studies.

The purpose of this review is to systematically examine the scientific evidence investigating selenium's relationship with COVID-19, aiming to support, or refute, the growing hypothesis that supplementation could prevent COVID-19 etiopathogenesis. In fact, immediately after the beginning of the COVID-19 pandemic, several speculative reviews suggested that selenium supplementation in the general population could act as a silver bullet to limit or even prevent the disease. Instead, a deep reading of the scientific reports on selenium and COVID-19 that are available to date supports neither the specific role of selenium in COVID-19 severity, nor the role of its supplementation in the prevention disease onset, nor its etiology.

Relationship between selenium status, selenoproteins and COVID-19 and other inflammatory diseases: A critical review.

The antioxidant effects of selenium as a component of selenoproteins has been thought to modulate host immunity and viral pathogenesis. Accordingly, the association of low dietary selenium status with inflammatory and immunodeficiency has been reported in the literature; however, the causal role of selenium deficiency in chronic inflammatory diseases and viral infection is still undefined. The COVID-19, characterized by acute respiratory syndrome and caused by the novel coronavirus 2, SARS-CoV-2, has infected millions of individuals worldwide since late 2019. The severity and mortality from COVID-19 have been associated with several factor, including age, sex and selenium deficiency. However, available data on selenium status and COVID-19 are limited, and a possible causative role for selenium deficiency in COVID-19 severity has yet to be fully addressed. In this context, we review the relationship between selenium, selenoproteins, COVID-19, immune and inflammatory responses, viral infection, and aging. Regardless of the role of selenium in immune and inflammatory responses, we emphasize that selenium supplementation should be indicated after a selenium deficiency be detected, particularly, in view of the critical role played by selenoproteins in human health. In addition, the levels of selenium should be monitored after the start of supplementation and discontinued as soon as normal levels are reached. Periodic assessment of selenium levels after supplementation is a critical issue to avoid over production of toxic metabolites of selenide because under normal conditions, selenoproteins attain saturated expression levels that limits their potential deleterious metabolic effects.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

The association between nutrients and occurrence of COVID-19 outcomes in the population of Western Iran: A cohort study.

INTRODUCTION: The study aimed to determine the association between nutrients (micronutrients, macronutrients, and antioxidants) and the occurrence of COVID-19-related outcomes (morbidity and hospitalization) using a cohort study in Western Iran. METHODS: The basic study information was collected from February 2019 to February 2020 from the baseline phase of the Dehgolan Prospective Cohort Study (DehPCS). The primary outcomes in this study included risk of contracting COVID-19 and hospitalization due to it at a specific time. To compare these outcomes based on different nutritional groups (macronutrients or micronutrients), Kaplan-Meier chart and log rank test were used. Also, univariate and multivariate regression models were used to investigate the association between different nutritional groups and desired outcomes (risk of contracting COVID-19 and hospitalization due to it at a certain time). RESULTS: The results showed that people having an insufficient intake of selenium (HR: 1.180; % 95 CI: 1.032-2.490; P: 0.042), vitamin A (HR: 1.119; % 95 CI: 1.020-1.442; p: 0.033), and vitamin E (HR: 1.544; % 95 CI: 1.136-3.093; p: 0.039) were significantly more infected with COVID-19 than the ones who had a sufficient intake of these nutrients. Also, the results showed that people having an insufficient intake of selenium (HR: 2.130; % 95 CI: 1.232-3.098; p: 0.018) and vitamin A (HR: 1.200; % 95 CI: 1.000-2.090; p: 0.043) were significantly hospitalized more than the ones who had a sufficient intake of these nutrients. CONCLUSION: Insufficient intake of selenium and vitamins A and E can significantly increase the incidence of COVID-19 and hospitalization due to it.

Effects of preharvest sprays of iodine, selenium and calcium on apple biofortification and their quality and storability.

The low dietary intake of iodine (I) and selenium (Se) by humans leads to serious health and socioeconomic problems. Therefore, enrichment of plants with I and Se using fertilisers containing these micronutrients is commonly recommended. In this study, we examined the impacts of combined spraying of I as iodide or iodate, Se as selenite or selenate, and calcium (Ca) as Ca-chloride on the enrichment of 'Red Jonaprince' (Malus domestica Borth.) apples, as well as fruit quality and their storability. Sprays were applied 2 weeks before harvest at rates of 0.5 kg I, 0.25 kg Se and 7 kg Ca per ha. Trees not sprayed with these nutrients served as controls. The tested sprays caused leaf burn, but they did not affect the cold injury of buds and shoots. Those sprays had no effect on yield, fruit size and russeting or skin colouring. At harvest, sprayed apples contained about 50 times more I and Se and 30% more Ca than the control fruit. After storage, compared to the control fruit, sprayed apples were firmer, had more organic acids and were less susceptible to disorders, such as bitter pit, internal breakdown and decay caused by Neofabraea spp. The results indicate that preharvest spraying with I, Se and Ca at high rates can be recommended to effectively enrich apples with I and Se and to simultaneously improve their storability.

Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, ß-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and ß-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and ß-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Selenium Status and Oxidative Stress in SARS-CoV-2 Patients.

Background and Objectives: Insufficient intake of essential micronutrient selenium (Se) increases the susceptibility to diseases associated with oxidative stress. The study aim was to assess Se status and oxidative stress in COVID-19 patients depending on severity of the disease. Materials and Methods: Blood plasma of 80 post-COVID-19 disease patients and 40 acutely ill patients were investigated. Concentration of Se was detected by a fluorometric method with di-amino-naphthalene using acidic hydrolysis. Selenoprotein P (Sepp1), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) and their metabolite adducts were evaluated by spectrophotometric methods using commercial assay kits. Results: Obtained results demonstrated that Se and Sepp1 concentration in acute patients were significantly (p < 0.05 for Se and p < 0.001 for Sepp1) decreased compared with post-COVID-19 disease patients. However, in post-COVID-19 disease patients, Se values were close to the low limit of the norm for the European population. 4-HNE adducts concentration as a marker of lipid peroxidation was significantly increased in the acute patients group compared to the recovery group (p < 0.001). Conclusions: COVID-19 pathology is characterized by the induction of oxidative stress and suppression of antioxidant defenses during the acute phase. Lower levels of Se and Sepp1 and higher levels of reactive oxygen species reflect this imbalance, highlighting the role of oxidative stress in the disease's pathogenesis.

Selenium intakes in the Irish adult population.

Selenium (Se) is an essential trace element which has an important role as a constituent of seleno-proteins involved in various physiological processes. Previous research in Irish adults suggests that intakes of this important nutrient are suboptimal. The aim of the present study was to estimate the current intakes and major food sources of Se by Irish adults. Mean daily intakes (MDIs) of Se were calculated using data from the National Adult Nutrition Survey which involved 1500 Irish adults aged 18-90 years. The Se content of foods and drinks consumed over a 4-d period was determined using data from the Irish Total Diet Study (TDS). Adequacy of Se intakes was assessed by calculating the proportion of the population with intakes below the adequate intake (AI) of 70 µg/d and lower reference nutrient intake of 40 µg/d (LRNI). The MDI of Se in the total population was 71⋅7 µg/d, with significantly higher intakes reported in men (80⋅2 µg/d) compared with women (63⋅4 µg/d, P < 0⋅01). Meat and meat products were the major contributing food group to Se intakes for both men (37 %) and women (31 %). Overall, 47 % of the population were not meeting the recommended AI, while 4 % of the total population were not meeting the LRNI. Although the average intake of Se is above the AI, a significant proportion of the population is not meeting this recommendation and continued monitoring of Se intakes is necessary, particularly by at-risk groups and also in the context of sustainability.

Selenoprotein P - Selenium transport protein, enzyme and biomarker of selenium status.

The habitual intake of selenium (Se) varies strongly around the world, and many people are at risk of inadequate supply and health risks from Se deficiency. Within the human organism, efficient transport mechanisms ensure that organs with a high demand and relevance for reproduction and survival are preferentially supplied. To this end, selenoprotein P (SELENOP) is synthesized in the liver and mediates Se transport to essential tissues such as the endocrine glands and the brain, where the "SELENOP cycle" maintains a privileged Se status. Mouse models indicate that SELENOP is not essential for life, as supplemental Se supply was capable of preventing the development of severe symptoms. However, knockout mice died under limiting supply, arguing for an essential role of SELENOP in Se deficiency. Many clinical studies support this notion, pointing to close links between health risks and low SELENOP levels. Accordingly, circulating SELENOP concentrations serve as a functional biomarker of Se supply, at least until a saturated status is achieved and SELENOP levels reach a plateau. Upon toxic intake, a further increase in SELENOP is observed, i.e., SELENOP provides information about possible selenosis. The SELENOP transcripts predict an insertion of ten selenocysteine residues. However, the decoding is imperfect, and not all these positions are ultimately occupied by selenocysteine. In addition to the selenocysteine residues near the C-terminus, one selenocysteine resides central within an enzyme-like environment. SELENOP proved capable of catalyzing peroxide degradation in vitro and protecting e.g. LDL particles from oxidation. An enzymatic activity in the intact organism is unclear, but an increasing number of clinical studies provides evidence for a direct involvement of SELENOP-dependent Se transport as an important and modifiable risk factor of disease. This interaction is particularly strong for cardiovascular and critical disease including COVID-19, cancer at various sites and autoimmune thyroiditis. This review briefly highlights the links between the growing knowledge of Se in health and disease over the last 50 years and the specific advances that have been made in our understanding of the physiological and clinical contribution of SELENOP to the current picture.

Association of COVID-19 mortality with serum selenium, zinc and copper: Six observational studies across Europe.

Introduction: Certain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe. Methods: Serum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory. Results: Median levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769). Discussion: The data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.

Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases.

Neglected tropical diseases (NTDs) encompass a group of infectious diseases with a protozoan etiology, high incidence, and prevalence in developing countries. As a result, economic factors constitute one of the main obstacles to their management. Endemic countries have high levels of poverty, deprivation and marginalization which affect patients and limit their access to proper medical care. As a matter of fact, statistics remain uncollected in some affected areas due to non-reporting cases. World Health Organization and other organizations proposed a plan for the eradication and control of the vector, although many of these plans were halted by the COVID-19 pandemic. Despite of the available drugs to treat these pathologies, it exists a lack of effectiveness against several parasite strains. Treatment protocols for diseases such as American trypanosomiasis (Chagas disease), leishmaniasis, and human African trypanosomiasis (HAT) have not achieved the desired results. Unfortunately, these drugs present limitations such as side effects, toxicity, teratogenicity, renal, and hepatic impairment, as well as high costs that have hindered the control and eradication of these diseases. This review focuses on the analysis of a collection of scientific shreds of evidence with the aim of identifying novel chalcogen-derived molecules with biological activity against Chagas disease, leishmaniasis and HAT. Compounds illustrated in each figure share the distinction of containing at least one chalcogen element. Sulfur (S), selenium (Se), and tellurium (Te) have been grouped and analyzed in accordance with their design strategy, chemical synthesis process and biological activity. After an exhaustive revision of the related literature on S, Se, and Te compounds, 183 compounds presenting excellent biological performance were gathered against the different causative agents of CD, leishmaniasis and HAT.

Iodine-Mediated Alkoxyselenylation of Alkenes and Dienes with Elemental Selenium.

A one-pot synthesis of linear and cyclic ß-alkoxyselenides is developed through the iodine-mediated three-component reaction of elemental selenium with alkenes (dienes) and alcohols. Selenylation of 1,5-hexadiene gives 2,5-di(methoxymethyl)tetrahydroselenophene and 2-methoxy-6-(methoxymethyl)tetrahydro-2H-selenopyran via the 5-exo-trig and 6-endo-trig cyclization. 1,7-Octadiene affords only linear 1:2 adduct with two terminal double bonds. 1,5-Cyclooctadiene results in one diastereomer of 2,6-dialkoxy-9-selenabicyclo [3.3.1]nonanes via 6-exo-trig cyclization. With 1,3-diethenyl-1,1,3,3-tetramethyldisiloxane, the first ring-substituted representative of a very rare class of heterocycles, 1,4,2,6-oxaselenadisilinanes, was obtained at a high yield.

Micronutrient deficiency risk in long-term enterally fed patients: A systematic review.

BACKGROUND AND AIMS: The micronutrient status of those receiving long-term enteral nutrition (EN) is poorly characterised. This systematic review was undertaken to determine prevalence of micronutrient deficiency in those receiving EN; the impact of the route of feeding; whether underlying disease or clinical factors were associated with micronutrient status; and the efficacy of interventions utilised to treat identified micronutrient deficiency. METHODS: Electronic databases (CINAHL, Embase, PubMed, Web of Science) were searched to June 2021 for publications of primary investigation of micronutrient status in adults or children (>5yrs) receiving EN for >2 months in their usual residence. Independent assessment of compliance with inclusion criteria (Covidence®), data extraction of predefined data points, assessment of basis (Academy of Dietetics Quality Checklist) and certainty of evidence (GRADE) was assessed by at least two authors. (PROSPERO Registration: CRD42021261113). RESULTS: Thirty-one studies (n = 744) met inclusion criteria. Deficiency was reported for copper, zinc, selenium, beta-carotene, and vitamins A, D and E: Only copper, zinc and selenium were associated with physical/haematological manifestations of deficiency. Jejunal feeding was associated with the development of copper deficiency and often required gastric or parenteral replacement to resolve the issue. Circumstances leading to deficiency included receiving feed products formulated with inadequate amounts of the implicated nutrient, low feed product volumes in the context of low macronutrient requirements, and nutritional decline prior to commencement of EN. Potential confounding factors such as inflammation were rarely accounted for. No studies investigated the contribution of underlying clinical condition on micronutrient status, and no other clinical or demographic features appeared to impact outcomes. Reported methods for treating identified deficiencies were usually successful in reversing deficiency symptoms. The certainty of evidence is very low, and the level of bias moderate to high. CONCLUSION: While the evidence is very uncertain about the effect of long-term enteral feeding on the development of micronutrient deficiencies, clinicians should be alert to the possibility of micronutrient deficiency developing in long-term EN fed patients. Those who may be at increased risk are those receiving nutrition into the jejunum, those who meet macronutrient requirements in low volumes of EN product, and those commencing EN in a nutritionally deplete state. Further research and surveillance of micronutrient status with contemporary EN products and practices is required.

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data.

OBJECTIVES: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). METHOD: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. RESULTS: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16). CONCLUSION: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Exploration of PDCoV-induced apoptosis through mitochondrial dynamics imbalance and the antagonistic effect of SeNPs.

Porcine Deltacoronavirus (PDCoV), an enveloped positive-strand RNA virus that causes respiratory and gastrointestinal diseases, is widely spread worldwide, but there is no effective drug or vaccine against it. This study investigated the optimal Selenium Nano-Particles (SeNPs) addition concentration (2 - 10 µg/mL) and the mechanism of PDCoV effect on ST (Swine Testis) cell apoptosis, the antagonistic effect of SeNPs on PDCoV. The results indicated that 4 µg/mL SeNPs significantly decreased PDCoV replication on ST cells. SeNPs relieved PDCoV-induced mitochondrial division and antagonized PDCoV-induced apoptosis via decreasing Cyt C release and Caspase 9 and Caspase 3 activation. The above results provided an idea and experimental basis associated with anti-PDCoV drug development and clinical use.

Can iron, zinc, copper and selenium status be a prognostic determinant in COVID-19 patients?

In severe COVID-19, the levels of iron (Fe), copper (Cu), zinc (Zn) and selenium (Se), do not only regulate host immune responses, but modify the viral genome, as well. While low serum Fe concentration is an independent risk factor for the increased death rate, Zn controls oxidative stress, synthesis of inflammatory cytokines and viral replication. Therefore, Zn deficiency associates with a worse prognosis. Although Cu exposure inactivates the viral genome and exhibits spike protein dispersal, increase in Cu/Zn due to high serum Cu levels, are correlated with enhanced risk of infections. Se levels are significantly higher in surviving COVID-19 patients. Meanwhile, both Zn and Se suppress the replication of SARS-CoV-2. Since the balance between the deficiency and oversupply of these metals due to a reciprocal relationship, has decisive effect on the prognosis of the SARS-CoV-2 infection, monitoring their concentrations may facilitate improved outcomes for patients suffering from COVID-19.

Molecular mechanisms and therapeutic effects of different vitamins and minerals in COVID-19 patients.

COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.

Selenium and mercury concentrations in biological samples from patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic disease affecting multiple organs. Furthermore, viral infection depletes several trace elements and promotes complex biochemical reactions in the body. Smoking has been linked to the incidence of COVID-19 and associated mortality, and it may impact clinical effects, viral and bacterial conversion, and treatment outcomes. OBJECTIVES: To study the relationship between severe acute respiratory syndrome coronavirus type 2 and the elemental concentrations of selenium (Se) and mercury (Hg) in biological samples from smokers and nonsmokers infected with the virus and in healthy individuals. METHOD: We evaluated changes in the concentrations of essential (Se) and toxic (Hg) elements in biological samples (blood, nasal fluid, saliva, sputum, serum, and scalp hair) collected from male smokers and nonsmokers (aged 29-59 years) infected with COVID-19 and from healthy men in the same age group. The patients lived in different cities in Sindh Province, Pakistan. The Se and Hg concentrations were determined using atomic absorption spectrophotometry. RESULTS: Se concentrations in all types of biological samples from smokers and nonsmokers with COVID-19 were lower than those of healthy smokers and nonsmokers. Hg concentrations were elevated in both smokers and nonsmokers with COVID-19. CONCLUSIONS: In the current study, persons infected with COVID-19 had higher concentrations of toxic Hg, which could cause physiological disorders, and low concentrations of essential Se, which can also cause weakness. COVID-19 infection showed positive correlations with levels of mercury and selenium. Thus, additional clinical and experimental investigations are essential.