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Major trace elements and their binding proteins in the early phase of Covid-19 infection

Nedić et al., JBIC Journal of Biological Inorganic Chemistry, doi:10.1007/s00775-022-01931-w
Feb 2022  
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Zinc for COVID-19
2nd treatment shown to reduce risk in July 2020
 
*, now with p = 0.00000064 from 45 studies, recognized in 17 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
Analysis of 60 COVID-19 patients and 60 matched controls, showing higher zinc levels in COVID-19 patients. The concentration of zinc was close to the lower reference limit in healthy people, and above the reference limit in 20 out of 60 COVID-19 patients. Authors note the increase for COVID-19 patients may be due to the use of zinc supplementation or cellular redistribution of zinc ions.
Nedić et al., 12 Feb 2022, USA, peer-reviewed, 6 authors. Contact: olgica@inep.co.rs.
This PaperZincAll
Major trace elements and their binding proteins in the early phase of Covid-19 infection
Olgica Nedić, Miloš Šunderić, Dragana Robajac, Goran Miljuš, Danilo Četić, Ana Penezić
JBIC Journal of Biological Inorganic Chemistry, doi:10.1007/s00775-022-01931-w
Metal ions seem to play important roles in the pathogenesis of the novel coronavirus disease of 2019 and are under investigation as potential prognostic markers and supplements in therapeutic procedures. The present study was aimed at assessing the relationship between the most abundant essential microelements (iron, zinc and copper) and their major binding proteins in the circulation in the early stage of infection. The concentration of zinc ions was measured to be higher in infected than in healthy persons, as well as ratios zinc/albumin and zinc/alpha-2-macroglobulin. Increased zinc levels could be attributed to cellular redistribution of zinc ions or to a use of zinc supplementation (zinc concentration was above the upper reference limit in one-third of infected individuals). Immunoblot analysis of protein molecular forms revealed that infected persons had greater amounts of proteinase-bound alpha-2-macroglobulin tetramer and albumin monomer than healthy individuals. The quantities of these forms were correlated with the concentration of zinc ions (r = 0.42 and 0.55, respectively) in healthy persons, but correlations were lost in infected individuals, most likely due to very high zinc concentrations in some participants which were not proportionally followed by changes in the distribution of protein species. Although we still have to wait for a firm confirmation of the involvement of zinc in beneficial defense mechanisms in patients with Covid-19, it seems that this ion may contribute to the existence of circulating protein forms which are the most optimal.
Declarations Conflict of interest There are no conflicts or competing interests to declare. Ethical approval Approval no. 02-286/4. Consent to participate Oral informed consent was obtained from participants regarding the use of their blood leftovers for the research purpose. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Nature Commun 11:5859', 'journal-title': 'Nature Commun'}, { 'key': '1931_CR38', 'doi-asserted-by': 'publisher', 'first-page': '1094', 'DOI': '10.1016/j.exger.2006.08.010', 'volume': '41', 'author': 'E Mocchegiani', 'year': '2006', 'unstructured': 'Mocchegiani E, Costarelli L, Giacconi R et al (2006) Zinc-binding ' 'proteins (metallothionein and alpha-2 macroglobulin) and ' 'immunosenescence. Exp Gerontol 41:1094–1107', 'journal-title': 'Exp Gerontol'}, { 'key': '1931_CR39', 'doi-asserted-by': 'publisher', 'first-page': '154', 'DOI': '10.1016/j.exger.2014.08.002', 'volume': '58', 'author': 'M Šunderić', 'year': '2014', 'unstructured': 'Šunderić M, Mihailović N, Nedić O (2014) Protein molecular forms of the ' 'insulin-like growth factor binding protein 2 change with ageing. Exp ' 'Gerontol 58:154–158', 'journal-title': 'Exp Gerontol'}, { 'key': '1931_CR40', 'doi-asserted-by': 'publisher', 'first-page': '379', 'DOI': '10.1007/s12263-013-0379-x', 'volume': '9', 'author': 'JR Nuttall', 'year': '2014', 'unstructured': 'Nuttall JR, Oteiza PI (2014) Zinc and the aging brain. Genes Nutr 9:379', 'journal-title': 'Genes Nutr'}, { 'key': '1931_CR41', 'doi-asserted-by': 'publisher', 'first-page': '61', 'DOI': '10.1007/s00775-018-1628-7', 'volume': '24', 'author': 'AZ Penezić', 'year': '2019', 'unstructured': 'Penezić AZ, Aćimović JM, Pavićević ID et al (2019) The interplay between ' 'copper(II), human serum albumin, fatty acids, and carbonylating agent ' 'interferes with Cys 34 thiol reactivity and copper binding. 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