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

Abstract

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.

Keywords: Aging; Immunity; Inflammation; Nutritional status; SARS-CoV-2; Selenium.

Fig. 1

The selenocysteinyl (Sec) residue in human glutathione peroxidase 1. Here a monomer is presented but the active form of the enzyme is homotetramer. The rare amino acid selenocysteine (Sec) is not found free in the body fluids of vertebrates, but it is found in the structure of 25 selenoproteins in the human body. The three-dimensional crystal structure (left) and the selenocysteinyl residue found in its active site are indicated in the left part in green with the Se atom in orange. The amino acids before (leucyl residue) and after (glycyl residue) the Sec are depicted with the free amino (NH) and carboxy groups (CO). The Se atom (orange) is depicted as the big ball linked to one hydrogen (white) forming the selenol group. The structures are based on the analysis of GPX1 performed by Epp; Ladenstein; Wendel (PDB ID: 1GP1). The hydrogen atoms were hidden for the sake of clarity (in the left). Details of Sec and the two adjacent amino acids (leucine and glycine) are shown on the right. The whole GPX1 structure and three amino acids (in the right) are depicted as sticks, except the selenol group (-SeH). The selenol group is represented by scaled balls.

Fig. 2

Inverted U-shaped relationship between Se status (in microgram/liter of serum) and risk of human disease.

Fig. 3

Schematic representation on how Se-dependent GPX (Se-GPX) indirectly modulate inflammation as originally proposed by McCarty . 5-HPETE, 5-hydroperoxyeicosatetraenoic acid; 5-LO, lipoxygenase; AA, arachidonic acid; COX, cyclooxygenase; GPX, glutathione peroxidase; GSH, reduced glutathione; GSSG, oxidized glutathione; HOOH, hydrogen peroxide; ROH, hydrogen oxidation; LT, leukotriene; Se, selenium; PGI, prostacyclin; PGI₂, prostaglandins; PLA₂, phospholipase A₂; TXA₂, thromboxane. Adapted from McCarty . ROOH can be either hydrogen peroxide (HOOH or H₂O₂) or lipid peroxides (ROOH) from biological membranes. GSH and GSSG represent reduced and oxidized glutathione. In this scheme, GPX1 and GPX4 modulates indirectly the inflammatory response by decreasing the steady-state levels of peroxides (peroxide tonus).

Fig. 4

The relationship of serum Se decreases with aging. The hypothetical decrease of Se as a function of age presented in the figure was qualitatively based on the study of Olivieri et al. ; Akbaraly et al. ; McKenzie et al. ; Cai; Zhang; Hongjun ; Steinbrenner et al. ; Lymbury et al. ; Almeida et al. ; Fujishima et al. .