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.
Highlights
Selenium (Se) is a unique trace element; it is the only one of the trace elements to be specified in the genetic code
We have presented above the evidence that shows an association between selenium species and SARS-CoV-2 or COVID-19 disease
As NF-κB is crucial for transcription of inflammatory cytokines associated with severe COVID-19 [109], further trials are needed to elucidate whether selenium supplementation can downregulate NF-κB expression in vivo and whether this confers a survival benefit
Summary
Selenium (Se) is a unique trace element; it is the only one of the trace elements to be specified in the genetic code. In the 1960s, Se toxicity (selenosis) was prevalent in Enshi County and, as late as 1981, intake was reported to be as high as 4990 μg/d in some areas of Enshi [9] With this remarkable degree of variation in intake, it is not surprising that there have been numerous examples of adverse health conditions linked to selenium deficiency including those caused by viruses [3,10] and by selenium excess [11]. There is a U-shaped relationship between Se intake or status and its health effects; that relationship is noticeable for selenium [11] In this comprehensive review we will explore the evidence for the involvement of selenium, whether as particular selenium species or selenoproteins, in viral infections. We will finish by discussing whether selenium supplementation might potentially benefit SARS-CoV-2 infec ted individuals, and if so, what the relevant dose might be
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