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

Zhang, Jinsong; Taylor, Ethan Will; Bennett, Kate; Saad, Ramy; Rayman, Margaret P.

doi:10.1093/ajcn/nqaa095

Cited by 318 publications

(368 citation statements)

References 12 publications

(31 reference statements)

Supporting

Mentioning

330

Contrasting

Unclassified

Order By: Relevance

“…Because NF-κB is an activator of many pro-inflammatory cytokines, including IL-6 ( 32 ), this could contribute to increased inflammation and the cytokine storms observed in COVID-19, and be a significant basis of pathogenic effects associated with SCoV2 infection of various tissues, including the lung, gastrointestinal tract and cardiovascular system. Importantly, these consequences of virus-mediated proteolysis would be taking place in everyone who is actively infected, regardless of their Se status , and would thus be consistent with results suggesting that Se intakes up to several times the minimal dietary requirement are associated with an increase in cure rate from COVID-19 ( 1 ). But people with suboptimal nutritional status could be particularly at risk, because their GSH and selenoprotein levels might be low to begin with, making them more vulnerable to the detrimental effects of virus-induced proteolysis.…”

Section: Discussionsupporting

confidence: 80%

“…Several independent studies have now established a significant association between the outcome of COVID-19 and previously documented regional selenium (Se) status in Chinese cities ( 1 ), and a similar relationship between serum Se and mortality in a European cohort of COVID-19 patients ( 2 ). These observations invite questions about the mechanisms involved, particularly because they fit into a consistent pattern of a role for Se that has been reported over several decades for a variety of RNA viruses (enteroviruses, hantaviruses, and influenza A) and viruses with an RNA stage (HIV-1 and Hepatitis B virus), as reviewed by various authors ( 3 – 5 ).…”

Section: Introductionmentioning

confidence: 79%

See 1 more Smart Citation

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Taylor

Radding

2020

Front. Nutr.

Self Cite

View full text Add to dashboard Cite

Glutathione peroxidases (GPX), a family of antioxidant selenoenzymes, functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Thus, it is highly significant that cytosolic GPX1 has been shown to interact with an inactive C145A mutant of M pro , the main cysteine protease of SARS-CoV-2, but not with catalytically active wild-type M pro . This seemingly anomalous result is what might be expected if GPX1 is a substrate for the active protease, leading to its fragmentation. We show that the GPX1 active site sequence is substantially similar to a known M pro cleavage site, and is identified as a potential cysteine protease site by the Procleave algorithm. Proteolytic knockdown of GPX1 is highly consistent with previously documented effects of recombinant SARS-CoV M pro in transfected cells, including increased reactive oxygen species and NF-κB activation. Because NF-κB in turn activates many pro-inflammatory cytokines, this mechanism could contribute to increased inflammation and cytokine storms observed in COVID-19. Using web-based protease cleavage site prediction tools, we show that M pro may be targeting not only GPX1, but several other selenoproteins including SELENOF and thioredoxin reductase 1, as well as glutamate-cysteine ligase, the rate-limiting enzyme for glutathione synthesis. This hypothesized proteolytic knockdown of components of both the thioredoxin and glutaredoxin systems is consistent with a viral strategy to inhibit DNA synthesis, to increase the pool of ribonucleotides for RNA synthesis, thereby enhancing virion production. The resulting “collateral damage” of increased oxidative stress and inflammation would be exacerbated by dietary deficiencies of selenium and glutathione precursors.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 79%

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Taylor

Radding

2020

Front. Nutr.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Se deficiency is also a risk factor for death from severe disease, as shown, e.g., in sepsis [14] or polytraumatic injury [15]. Notably, the cure rate from COVID-19 was recently associated with basal Se status in different areas of China [16]. Collectively, the available studies support the notion that Se may be of relevance for infection with SARS-CoV-2 and disease course of COVID-19 [17][18][19].…”

Section: Introductionmentioning

confidence: 66%

“…The present care on the ICU over long periods of time constitutes a fundamental different situation, where the constant suppression of hepatic SELENOP biosynthesis may require supplemental measures in the long run [39]. Concordant with this notion, the hypothesized association of low Se status with impaired recovery was reported from an in silico analysis of cure rates from COVID-19 in the different areas of China with diverging baseline Se status [16].…”

Section: Discussionmentioning

confidence: 83%

Selenium Deficiency Is Associated with Mortality Risk from COVID-19

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

“…When the cure rate (%) in cities outside Hubei province was plotted against population hair Se concentration (a surrogate for Se intake), a significant, positive linear association was shown, with a Pearson r of 0.85 (p<0.0001). 4 Consistently, a German study found that serum Se and SELENOP concentrations in COVID-19 patients were significantly lower than healthy controls, and Se status was significantly higher in samples from surviving COVID patients than in those of non-survivors. 5 Relevant to these observations, ebselen, an organoselenium compound, was found to have the strongest inhibitory activity out of 10,000 compounds examined (the current drug arsenal) against the SARS-CoV-2 main protease, which mediates the life cycle of the virus and is a well-recognized target for inhibition.…”

Section: Introductionmentioning

confidence: 80%

SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, endoplasmic reticulum stress and DNA synthesis

Wang

Huang

Sun

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

A significant, positive association between selenium status and COVID-19 prognosis has recently been identified. The present study investigated the influence of SARS-CoV-2 on host selenoproteins which mediate many beneficial actions of selenium. We found that SARS-CoV-2 suppressed mRNA expression of selenoproteins associated with ferroptosis (GPX4), ER stress (SELENOF, SELENOK, SELENOM and SELENOS) and DNA synthesis (TXNRD3) in Vero cells, providing a deeper insight into the connection between selenium and SARS-CoV-2.

show abstract

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

Cited by 318 publications

References 12 publications

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?

Selenium Deficiency Is Associated with Mortality Risk from COVID-19

SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, endoplasmic reticulum stress and DNA synthesis

Contact Info

Product

Resources

About