† A COVID-19 case in a fully vaccinated person occurred when SARS-CoV-2 RNA or antigen was detected in a respiratory specimen collected ≥14 days after completing the primary series of a COVID-19 vaccine with Food and Drug Administration (FDA) approval or emergency use authorization. The COVID-19 case definition, including criteria to distinguish a new case from an existing case, is per the July 2021 update to the national standardized surveillance case definition and national notification for 2019 novel coronavirus disease (COVID-19) (21-ID-01) (https://ndc.services.cdc.gov/case-definitions/ coronavirus-disease-2019-2021/). Fully vaccinated persons were those with a completed primary series of 2 doses of the Pfizer-BioNTech or Moderna mRNA vaccine or a single dose of the Janssen vaccine (https://www.cdc.gov/ coronavirus/2019-ncov/vaccines/stay-up-to-date.html). A COVID-19 case in an unvaccinated person occurred when the person did not receive any FDAauthorized COVID-19 vaccine doses before the specimen collection date. Cases were excluded in partially vaccinated persons who received at least one FDAauthorized or approved vaccine dose but did not complete a primary series ≥14 days before collection of a respiratory specimen with SARS-CoV-2 RNA or antigen detected. Ascertaining vaccination status for COVID-19 patients through active linkage of case surveillance and immunization information systems typically assumes that cases among persons who are unmatched to the registry are unvaccinated. This analysis represents the combined impact of the Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccines, which had different clinical efficacies against confirmed infection. Information on different FDA-authorized and approved COVID-19 vaccine products, including clinical efficacy, is available online. https://www.cdc.gov/coronavirus/2019-ncov/ vaccines/different-vaccines.html

The pharmacokinetics and utilization (flavocoenzyme synthesis) of orally and intravenously administered riboflavin in healthy humans were assessed. After the determination of circadian rhythms of riboflavin concentrations in blood plasma and urine of four males and five females (control period), each of these subjects received three different oral riboflavin doses (20, 40, and 60 mg) and one intravenous bolus injection of riboflavin (11.6 mg). Vitamins were administered in a randomized, cross-over design with 2 wk between each administration. Blood plasma and urine specimens were collected repeatedly over a period of 48 h after each administration. Concentrations of flavocoenzymes and riboflavin were analyzed in blood plasma; riboflavin was assayed in urine. During the control period, a small circadian variation was observed: plasma concentrations and urinary excretion of riboflavin were low during the afternoon (P < 0.05). Pharmacokinetics were calculated using a two-compartment open model. The maximal amount of riboflavin that can be absorbed from a single dose was 27 mg per adult. Half-life of absorption was 1.1 h. First-order rate constants describing distribution and elimination of riboflavin were significantly higher after intravenous than after oral administration (P < 0.01). Release of flavocoenzymes into plasma was low compared with the increase of riboflavin concentrations. 7 alpha-Hydroxyriboflavin was identified in plasma. Clearance data indicated that urinary excretion of riboflavin contributes to one-half of the overall removal of riboflavin from plasma. No sex differences were observed for any of the pharmacokinetic variables (P > 0.05).

The significance of metal ions in biological systems is currently obvious. For example, the functioning of many enzymes is metal ion dependent.'t2 Enzymes contain metal ions a t their active sites, for example, Zn2+ in dihydro~rotase,~ carboxypeptidase, and carbonic anhydrase, Mn2+ in isocitric dehydrogenase and malic enzyme, and Mg2+ in enolase and a variety of kinase^.^ Other enzymes appear to require the presence of an ion, frequently a monovalent one such as Na+, K+, or NH4+, for stabilization of the particular conformation responsible for maximal catalytic a~t i v i t y .~ Recently, Gillard5 summarized the possible reactions at an active site of a metal ion potentiated enzyme in the following way. (a) The metal ion may induce, by coordination, a specific "lock" geometry of the apoprotein metal binding site so that only certain substrates are able to become attached to the framework produced. (b) The metal ion may activate a bond or bonds of the substrate (or the protein) through coordination. This is quite feasible, since it may well be that the metal binding site of the apoprotein has a constant geometry, whether or not the metal ion is present. (c) The metal ion may induce by coordination a specific "key" geometry of the substrate so that it will fit the "lock" of the apoprotein specifically.Besides the question about the functions of the metal ion, there are others such as: which are the factors that determine the coordination of metal ions to ligands, for example, in biological fluids or enzymemetal ion-substrate complexes? For the special case of the latter, some of the general questions6 that arise can be formulated in the following way. (I) What are the reasons for the "right" metal ion coordinating a t the "right" enzyme (or substrate)? (5) R. D. Gillard, Inorg. Chim. Acta Rev., 1, 69 (1967). (6) H. Sigel, Chimia (Aarau), 21,489 (1967).(11) How great is the coordination tendency of the remaining coordination positions of such a bound metal ion? Does the first coordinated ligand influence the type of ligand which may be coordinated at further coordination sites? EM#: $1 '\ ? $ -; M + 1 ) e CJ)(111) Why does the "right" substrate, i.e., the substrate that can be converted to products by a special enzyme, coordinate to the "right" enzyme-metal ion complex (or the "right" enzyme to the "right" substratemetal ion complex)?f ' s All these questions are closely connected with each other and can be summarized in one question: what are the control mechanisms that determine the coordination and coordination tendency of metal ions? This article is an attempt to answer this question as far as our current understanding and available space allow. Kind of Metal Ions and Their Availability. Metalions that all living organisms require are sodium, potassium, magnesium calcium, manganese, iron, cobalt, copper, and zinc. In addition, there are small quantities of vanadium, chromium, molybdenum, niobium, and cadmium in particular organism^.^ According to william^,^ these metal ions can conveniently be divided with regard...

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