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

Abstract

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. In this review, we address the question whether Se intake is a factor in determining the severity of response to coronavirus disease 2019 (COVID-19). Emphasis is placed on epidemiological and animal studies which suggest that Se affects host response to RNA viruses and on the molecular mechanisms by which Se and selenoproteins modulate the inter-linked redox homeostasis, stress response and inflammatory response. Together these studies indicate that Se status is an important factor in determining the host response to viral infections. Therefore, we conclude that Se status is likely to influence human response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and that Se status is one (of several) risk factors which may impact on the outcome of SARS-CoV-2 infection, particularly in populations where Se intake is sub-optimal or low. We suggest the use of appropriate markers to assess the Se status of COVID-19 patients and possible supplementation may be beneficial in limiting the severity of symptoms, especially in countries where Se status is regarded as sub-optimal.

Keywords: COVID-19; Inflammation; Micronutrients; Redox status; Selenium; Severe acute respiratory syndrome coronavirus 2; Viral infection.

Fig. 1.

Selenium and response to viral infection. In humans, dietary selenium is incorporated into twenty-five selenoproteins as the amino acid selenocysteine. Selenoproteins include glutathione peroxidases (GPX), 15 kDa selenoprotein F (SELENOF), selenoproteins K and S and thioredoxin reductases (TXNRD). They play crucial roles in molecular pathways such as oxidative stress response, redox control and mitochondrial function, as well as endoplasmic reticulum (ER) stress and unfolded protein responses (UPR), and immune and inflammatory response in particular involving NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2) signalling. Cross-talk between these pathways has been shown to be key to produce an adequate response to viral infections, and low selenium status has been linked to poorer response to RNA virus infection in human studies, and animal and cell culture models. The diagram illustrates how reduced expression of selenoproteins as a result of low/sub-optimal selenium status could alter molecular pathways involved in stress responses and contribute to an aggressive pro-inflammatory environment leading to poorer disease prognosis.

Fig. 2.

Hypothetical model of the impact of selenium on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Disease outcome of a coronavirus disease 2019 (COVID-19) patient is influenced by age, obesity and the presence of co-morbidities such as type 2 diabetes (T2D), CVD and by being immunocompromised. Based on the current knowledge of the effects of selenium status on RNA virus infections, it can be speculated that patients with low/sub-optimal selenium status and reduced selenoprotein expression could be at higher risk of poor disease outcome. This could be influenced not only by dietary intake but also by genotype for a number of genetic variants in selenoprotein genes. Nutritional intervention such as selenium supplementation with selenomethionine (SeMet) or sodium selenite (Na₂SeO₃) may therefore improve disease outcomes for individuals with sub-optimal selenium status. Furthermore, therapeutic interventions may also include synthetic selenium compounds such as ebselen that has been found to inhibit SARS-CoV-2 main protease (M^pro). ACE2, angiotensin-converting enzyme 2.