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.

Eukaryotic translation initiation factor eIF-4E plays a central role in the recognition of the 7-methylguanosine-containing cap structure of mRNA and the formation of initiation complexes during protein synthesis. eIF-4E exists in both phosphorylated and nonphosphorylated forms, and the primary site of phosphorylation has been identified. Previous studies have suggested that eIF-4E phosphorylation facilitates its participation in protein synthesis. However, the biochemical basis for the functional difference between the two forms of eIF-4E is unknown. To address this directly, we have developed a method for the separation of phosphorylated and nonphosphorylated eIF-4E from rabbit reticulocytes by chromatography on rRNA-Sepharose. Using the resultant purified forms, we have studied the protein's interaction with the cap analogs m7GTP and m7GpppG and with the cap of globin mRNA by fluorescence quenching of tryptophan residues. It was found that phosphorylated eIF-4E had 3-to 4-fold greater affinity for cap analogs and mRNA than nonphosphorylated eIF-4E. The equilibrium binding constants (x 105, expressed as M-1) for the interaction of phosphorylated eIF-4E with m7GTP, m7GpppG, and globin mRNA were 20.0 ± 0.1, 16.4 ± 0.1, and 31.0 ± 0.1, respectively, whereas those for the nonphosphorylated form were 5.5 ± 0.4, 4.3 ± 0.4, and 10.0 ± 0.1, respectively. Treatment with potato acid phosphatase converted the phosphorylated form to the nonphosphorylated form and decreased the binding constant for m7GTP by a factor of3. The increased affinity for mRNA caps may account for the in vivo and in vitro correlations between eIF-4E phosphorylation and accelerated protein synthesis and cell growth.Except in unusual circumstances such as virus infection, cellular stress, or deprivation of nutrients, the overall rate of protein synthesis in eukaryotic cells is thought to be determined by the rate of formation of 48S initiation complexes. This is based on the observations that 48S complexes are present at very low steady-state levels compared with other initiation complexes (1), usually being detected only in the presence of inhibitors (2), and that the ATP-dependent step ofinitiation is rate-limiting (3). Formation ofthe 48S initiation complex involves the binding of mRNA to the 43S initiation complex and is catalyzed by group 4 initiation factors (reviewed in refs. 4-6). The four polypeptides of the eIF-4 group-eIF-4A, eIF-4B, eIF-4E, and eIF-41-collectively bind to the m7GTP-containing cap, unwind mRNA secondary structure at the expense of ATP, and facilitate the movement of the 40S ribosomal subunit along the mRNA until the initiation codon is reached. Various complexes of the eIF-4 polypeptides have been isolated, the best studied of which is termed eIF-4F. eIF-4F isolated from mammalian cells was originally shown to contain the polypeptides eIF-4A, eIF-4E, and eIF-4y (7, 8), but other purifications yield a twocomponent factor consisting of eIF-4E and eIF-4y (9-11). Similarly, eIF-4F and eIF(iso)-4F from plants (12) and ...