Geographical distribution of trace elements (selenium, zinc, iron, copper) and case fatality rate of COVID-19: a national analysis across conterminous USA.

Severe outcome particularly death is the largest burden of COVID-19. Clinical observations showed preliminary data that deficiency in certain trace elements, essential for the normal activity of immune system, may be associated with worse COVID-19 outcome. Relevant study of environmental epidemiology has yet to be explored. We investigated the geographical association between concentrations of Se, Zn, Fe and Cu in surface soils and case fatality rate of COVID-19 in USA. Two sets of database, including epidemiological data of COVID-19 (including case fatality rate, from the University of John Hopkinson) and geochemical concentration data of Se, Zn, Fe and Cu in surface soils (from the National Geochemical Survey), were mapped according to geographical location at the county level across conterminous USA. Characteristics of population, socio-demographics and residential environment by county were also collected. Seven cross-sectional sampling dates, with a 4-week interval between adjacent dates, constructed an observational investigation over 24 weeks from October 8, 2020, to March 25, 2021. Multivariable fractional (logit) outcome regression analyses were used to assess the association with adjustment for potential confounding factors. In USA counties with the lowest concentration of Zn, the case fatality rate of COVID-19 was the highest, after adjustment for other influencing factors. Associations of Se, Fe and Cu with case fatality rate of COVID-19 were either inconsistent over time or disappeared after adjustment for Zn. Our large study provides epidemiological evidence suggesting an association of Zn with COVID-19 severity, suggesting Zn deficiency should be avoided.

A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: an in silico investigation.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of -6.7 kcal/mol compared with the -6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.

Association between fatality rate of COVID-19 and selenium deficiency in China.

BACKGROUND: COVID-19 has impacted populations around the world, with the fatality rate varying dramatically across countries. Selenium, as one of the important micronutrients implicated in viral infections, was suggested to play roles. METHODS: An ecological study was performed to assess the association between the COVID-19 related fatality and the selenium content both from crops and topsoil, in China. RESULTS: Totally, 14,045 COVID-19 cases were reported from 147 cities during 8 December 2019-13 December 2020 were included. Based on selenium content in crops, the case fatality rates (CFRs) gradually increased from 1.17% in non-selenium-deficient areas, to 1.28% in moderate-selenium-deficient areas, and further to 3.16% in severe-selenium-deficient areas (P = 0.002). Based on selenium content in topsoil, the CFRs gradually increased from 0.76% in non-selenium-deficient areas, to 1.70% in moderate-selenium-deficient areas, and further to 1.85% in severe-selenium-deficient areas (P < 0.001). The zero-inflated negative binomial regression model showed a significantly higher fatality risk in cities with severe-selenium-deficient selenium content in crops than non-selenium-deficient cities, with incidence rate ratio (IRR) of 3.88 (95% CIs: 1.21-12.52), which was further confirmed by regression fitting the association between CFR of COVID-19 and selenium content in topsoil, with the IRR of 2.38 (95% CIs: 1.14-4.98) for moderate-selenium-deficient cities and 3.06 (1.49-6.27) for severe-selenium-deficient cities. CONCLUSIONS: Regional selenium deficiency might be related to an increased CFR of COVID-19. Future studies are needed to explore the associations between selenium status and disease outcome at individual-level.