COVID-19 and Selenium

An Exploratory Study of Selenium Status in Normal Subjects and COVID-19 Patients in South Indian population: Case for Adequate Selenium Status: Selenium Status in COVID-19 Patients

Muhammed Majeed, Kalyanam Nagabhushanam, Sujay Gowda, Lakshmi Mundkur
Nutrition, 2020, 111053
ISSN 0899-9007
doi: 10.1016/j.nut.2020.111053.
(http://www.sciencedirect.com/science/article/pii/S0899900720303361)

Abstract: The pandemic of acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected millions of individuals, causing major health and economic disruption worldwide. Although the numbers of infections are declining in some parts of the World, new infections are steadily rising in India. Nutrition and immune status are two critical aspects of fighting the virus successfully. Recently, the selenium status was reported to positively correlate with the survival of COVID patients as compared with non-survivors. We analysed the blood serum levels in apparently healthy (N=30) individuals and those with confirmed COVID -19 infection(N=30) in the southern part of India. Patients showed a significantly lower selenium level of 69.2 ±8.7 ng/ml than controls 79.1 ± 10.9 ng/ml, the difference was statistically significant (P=0.0003). Interestingly the controls showed a borderline level of selenium, suggesting that the level of this micronutrient is not optimum in the population studied. The results of this exploratory study pave the way for further research in a larger population and suggest that selenium supplementation may be helpful to reduce the impact of the virus.
Keywords: Micronutrient; Immune response; inflammation; Selenium status; Viral infection; COVID -19

Association between regional selenium status and reported outcome of COVID-19 cases in China

Jinsong Zhang, Ethan Will Taylor, Kate Bennett, Ramy Saad, Margaret P Rayman
The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1297–1299
doi: https://doi.org/10.1093/ajcn/nqaa095

Dear Editor:

Potentially relevant to the recent appearance of COVID-19 in China is the fact that there is a belt of selenium deficiency running from northeast to southwest in the country and, indeed, China has populations that have both the lowest and the highest selenium status in the world (1). A set of interesting studies published by the Beck laboratory in the 1990s showed that host selenium deficiency increased the virulence of RNA viruses such as coxsackievirus B3 and influenza A (2, 3). Passage through a selenium-deficient animal that was unable to produce sufficient antioxidant selenoproteins for its own protection resulted in the virus mutating to a virulent form that caused more severe pathology (2, 3). Those findings shed light on a human selenium-deficiency disease, a cardiomyopathy known as Keshan disease, named after the area in northeast China where it was endemic. The disease showed a seasonal variation, suggesting a viral cofactor that was later identified as coxsackievirus B3 (2). When the population was supplemented with selenium, the incidence of Keshan disease decreased dramatically

Application and interpretation of Mendelian randomization approaches in exploring the causality between folate and coronary artery disease

Peng-Fei Wu, Wan Zhang, Xinghao Zhang, Rongsen Zhang
The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1299–1300
doi: https://doi.org/10.1093/ajcn/nqaa069

Dear Editor:

It has long been disputed whether folate deficiency plays a causal role in cardiovascular disease and whether folate fortification should be promoted worldwide. Recently we read with great interest the article by Long et al. (1) that aimed at investigating the association, possibly causation, between serum folate and coronary artery disease (CAD) in a Chinese population. We applaud the authors for rigorously completing observational epidemiological analyses based on a nested case-control study. Nevertheless, we wish to comment on their subsequent findings through Mendelian randomization (MR) approaches.

Selenium and RNA Virus Interactions: Potential Implications for SARS-CoV-2 Infection (COVID-19)

Hiffler L and Rakotoambinina B (2020)
Front. Nutr. 7:164.
Nutrients. 2020 Aug 7;12(8):2358.
doi: 10.3389/fnut.2020.00164

SARS-CoV-2 is an RNA virus responsible for the COVID-19 pandemic that already claimed more than 340,000 lives worldwide as of May 23, 2020, the majority of which are elderly. Selenium (Se), a natural trace element, has a key and complex role in the immune system. It is well-documented that Se deficiency is associated with higher susceptibility to RNA viral infections and more severe disease outcome. In this article, we firstly present evidence on how Se deficiency promotes mutations, replication and virulence of RNA viruses. Next, we review how Se might be beneficial via restoration of host antioxidant capacity, reduction of apoptosis and endothelial cell damages as well as platelet aggregation. It also appears that low Se status is a common finding in conditions considered at risk of severe COVID-19, especially in the elderly. Finally, we present a rationale for Se use at different stages of COVID-19. Se has been overlooked but may have a significant place in COVID-19 spectrum management, particularly in vulnerable elderly, and might represent a game changer in the global response to COVID-19.

Early Nutritional Interventions with Zinc, Selenium and Vitamin D for Raising Anti-Viral Resistance Against Progressive COVID-19

Alexander, J.; Tinkov, A.; Strand, T.A.; Alehagen, U.; Skalny, A.; Aaseth, J.
Nutrients. 2020 Aug 7;12(8):2358.
doi: 10.3390/nu12082358

Abstract
Objectives: The novel coronavirus infection (COVID-19) conveys a serious threat globally to health and economy because of a lack of vaccines and specific treatments. A common factor for conditions that predispose for serious progress is a low-grade inflammation, e.g., as seen in metabolic syndrome, diabetes, and heart failure, to which micronutrient deficiencies may contribute. The aim of the present article was to explore the usefulness of early micronutrient intervention, with focus on zinc, selenium, and vitamin D, to relieve escalation of COVID-19. Methods: We conducted an online search for articles published in the period 2010–2020 on zinc, selenium, and vitamin D, and corona and related virus infections. Results: There were a few studies providing direct evidence on associations between zinc, selenium, and vitamin D, and COVID-19. Adequate supply of zinc, selenium, and vitamin D is essential for resistance to other viral infections, immune function, and reduced inflammation. Hence, it is suggested that nutrition intervention securing an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome – coronavirus-2) and mitigate the course of COVID-19. Conclusion: We recommended initiation of adequate supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority as regards this nutritive adjuvant therapy, which should be started prior to administration of specific and supportive medical measures.
Keywords: COVID-19; corona virus; nutritional; therapy; micronutrients; selenium; zinc; vitamin A; vitamin D; coenzyme Q,sub>10

Selenium Deficiency Is Associated with Mortality Risk from COVID-19

Moghaddam, A.; Heller, R.A.; Sun, Q.; Seelig, J.; Cherkezov, A.; Seibert, L.; Hackler, J.; Seemann, P.; Diegmann, J.; Pilz, M.; Bachmann, M.; Minich, W.B.; Schomburg, L.
Nutrients 2020, 12, 2098.
doi: 10.3390/nu12072098.

Abstract: SARS-CoV-2 infections underlie the current coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. The mortality risk from a severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n = 166) from COVID-19 patients (n = 33) were collected consecutively and analyzed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r = 0.7758, p < 0.001), pointing to an insufficient Se availability for optimal selenoprotein expression. In comparison with reference data from a European cross-sectional analysis (EPIC, n = 1915), the patients showed a pronounced deficit in total serum Se (mean ± SD, 50.8 ± 15.7 vs. 84.4 ± 23.4 µg/L) and SELENOP (3.0 ± 1.4 vs. 4.3 ± 1.0 mg/L) concentrations. A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L, was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared with non-survivors (Se; 53.3 ± 16.2 vs. 40.8 ± 8.1 µg/L, SELENOP; 3.3 ± 1.3 vs. 2.1 ± 0.9 mg/L), recovering with time in survivors while remaining low or even declining in non-survivors. We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion of a relevant role of Se for COVID convalescence and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.
Keywords: trace element; inflammation; selenoprotein P; micronutrient; COVID-19

Selenium, Selenoproteins, and Immunity.

Avery, J.C.; Hoffmann, P.R.
Nutrients 2018, 10, 1203.
doi: 10.3390/nu10091203.

Abstract: Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.
Keywords: selenocysteine; macrophage; T cell; antibody; inflammation; cancer

Selenium and selenoproteins in viral infection with potential relevance to COVID-19

Jinsong Zhang, Ramy Saad, Ethan Will Taylor, Margaret P. Rayman
Redox Biology, Volume 37, 2020, 101715
ISSN 2213-2317
doi: 10.1016/j.redox.2020.101715.
(http://www.sciencedirect.com/science/article/pii/S2213231720309204)

Abstract: Selenium is a trace element essential to human health largely because of its incorporation into selenoproteins that have a wide range of protective functions. Selenium has an ongoing history of reducing the incidence and severity of various viral infections; for example, a German study found selenium status to be significantly higher in serum samples from surviving than non-surviving COVID-19 patients. Furthermore, a significant, positive, linear association was found between the cure rate of Chinese patients with COVID-19 and regional selenium status. Moreover, the cure rate continued to rise beyond the selenium intake required to optimise selenoproteins, suggesting that selenoproteins are probably not the whole story. Nonetheless, the significantly reduced expression of a number of selenoproteins, including those involved in controlling ER stress, along with increased expression of IL-6 in SARS-CoV-2 infected cells in culture suggests a potential link between reduced selenoprotein expression and COVID-19-associated inflammation. In this comprehensive review, we describe the history of selenium in viral infections and then go on to assess the potential benefits of adequate and even supra-nutritional selenium status. We discuss the indispensable function of the selenoproteins in coordinating a successful immune response and follow by reviewing cytokine excess, a key mediator of morbidity and mortality in COVID-19, and its relationship to selenium status. We comment on the fact that the synthetic redox-active selenium compound, ebselen, has been found experimentally to be a strong inhibitor of the main SARS-CoV-2 protease that enables viral maturation within the host. That finding suggests that redox-active selenium species formed at high selenium intake might hypothetically inhibit SARS-CoV-2 proteases. We consider the tactics that SARS-CoV-2 could employ to evade an adequate host response by interfering with the human selenoprotein system. Recognition of the myriad mechanisms by which selenium might potentially benefit COVID-19 patients provides a rationale for randomised, controlled trials of selenium supplementation in SARS-CoV-2 infection.
Keywords: SARS-CoV-2; COVID-19; Selenium; Selenoproteins; Redox-active selenium species; Ebselen

Selenium and viral infection: Are there lessons for COVID-19?

Bermano, G., Méplan, C., Mercer, D., & Hesketh, J. (2020).
British Journal of Nutrition, 1-10.
doi:10.1017/S0007114520003128

Se is a micronutrient essential for human health. Sub-optimal Se status is common, occurring in a significant proportion of the population across the world including parts of Europe and China. Human and animal studies have shown that Se status is a key determinant of the host response to viral infections…

Selenium supplementation in the prevention of coronavirus infections (COVID-19)

Marek Kieliszek, Boguslaw Lipinski
Medical Hypotheses, Volume 143, 2020, 109878
ISSN 0306-9877
doi: 10.1016/j.mehy.2020.109878.
(http://www.sciencedirect.com/science/article/pii/S030698772031104X)

Abstract: Selenium (Se) is a ubiquitous element akin to sulfur (S) existing in the Earth crust in various organic and inorganic forms. Selenium concentration varies greatly depending on the geographic area. Consequently, the content of selenium in food products is also variable. It is known that low Se is associated with increased incidence of cancer and heart diseases. Therefore, it is advisable to supplement diet with this element albeit in a proper form. Although blood increased concentrations of Se can be achieved with various pharmacological preparations, only one chemical form (sodium selenite) can offer a true protection. Sodium selenite, but not selenate, can oxidize thiol groups in the virus protein disulfide isomerase rendering it unable to penetrate the healthy cell membrane. In this way selenite inhibits the entrance of viruses into the healthy cells and abolish their infectivity. Therefore, this simple chemical compound can potentially be used in the recent battle against coronavirus epidemic.
Keywords: SARS-CoV-2; COVID-19; Coronavirus; Selenium

COVID-19: Review outlines Selenium supplementation action plan

14-Sep-2020 By Nikki Hancocks

Selenium (Se) deficiency has a ‘striking’ yet overlooked link with COVID-19 severity, researchers have argued in a review which outlines a supplementation action plan.