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On the reduction of COVID-19 associated case fatality rate: reckoning of a physicist

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We argue that the human immune system is perfectly equipped to tackle SARS-CoV-2 virus and COVID-19 associated case fatality rate (C.F.R.) can be largely reduced by improving the zinc dietary intake and zinc cellular absorption (via Zn2+ ionophores for the elderly – chloroquine, possibly quinine or clioquinol). Question for the readers: Does the classic anti-malarial Quinine work as a zinc ionophore and/or inhibitor of endosomal acidification (like the chloroquine)?
On the reduction of COVID-19 associated case fatality rate
: reckoning of a physicist
Върху намалението на степента на смъртност
от COVID-19: мислите на физик
Victor Atanasov
/ Виктор Атанасов
Sofia University, Faculty of Physics, 5 blvd J. Bourchier 1164 Sofia, Bulgaria / Софийски Университет,
Физически Факултет, бул. Дж. Баучер 5, 1164 София, България
We argue that the human immune system is perfectly equipped to tackle SARS-CoV-2 virus and COVID-19
associated case fatality rate (C.F.R.) can be largely reduced by improving the zinc dietary intake and zinc
cellular absorption (via Zn2+ ionophores for the elderly).
Твърдим, че имунната система на човека е перфектно оборудвана за справяне с вируса SARS-CoV-2 и
COVID-19 свързаната степен на смъртност (С.С.) може значително да се намали чрез подобряване на
приема на цинк чрез диетата и клетъчната абсорбция на цинка (чрез Zn2+ йонофори за възрастните
Key words: SARS-CoV-2, 2019-nCoV, COVID-19, coronavirus / ключови думи: САРС-КоВ-2, 2019-нКоВ,
КОВИД-19, корона вирус
Date/Дата: 17/03/2020
English lang. text/Текст на англ. език
The Observables associated with COVID-19 include [1]:
1. 80.9% of people will get over the SARS-CoV-2 virus infection (and COVID-19 disease) with mild or no symptoms at all.
2. COVID-19 is mild if present at all in children under 9 years of age (0% C.F.R.).
3. COVID-19 is manifest with progressively increasing C.F.R. as a function of the age ( 10-39y 0.2%; 40-49y 0.4%; 50-59y
1.3%; 60-69y 3.6%; 70-79y 8% and >80y 14.8%).
4. COVID-19 associated C.F.R. is sex dependent with bias towards men. Male’s C.F.R. of 2.8% and is markedly higher than
female’s 1.7%.
5. COVID-19 associated C.F.R. dominates in the retiree occupation group 5.1%.
6. COVID-19 associated C.F.R. increases with the presence of comorbidities: cardiovascular disease 10.5%; diabetes 7.3%;
chronic respiratory disease/ hypertension 6%; cancer 5.6%.
7. Hemoglobin median concentration (in g/L) in ICU
care patients is 122, while for non-ICU care patients is 130.5, with little
statistical significance (p=0.2) [2].
The first observable is key to conquering the panic over the present lack of a vaccine and/or a specific virus chemotherapy, that is the
identification (approval) of a small molecule capable of a.) inhibiting the virus replication; b.) achieving therapeutic concentrations in
affected tissues (lung, heart, intestines) in vivo and c.) being non-toxic.
The first observable is a proof that the human immune system is perfectly equipped to tackle the virus, therefore disease C.F.R. is
mainly rooted in its improper functioning.
Naturally, we pose the question: What is the most likely reason for the immune system dysfunction, which leads to non-negligible
COVID-19 associated C.F.R. and is capable of explaining away the rest of the observables as self-evident?
For the purpose of working out an answer to the question, we would raise a hypothesis based on the recommended Chinese treatment
with chloroquine [3,4]. The almost universal anti-viral action of chloroquine (an inhibitor of endosomal acidification) is mainly
associated with inhibiting pH-dependent steps of the viral replication[5].
Case Fatality Rate C.F.R. = #deaths/(#deaths + #recovered); 2.3% according to [1].
Степен на Смъртност С.С. = #смъртни случаи/(# смъртни случаи + # излекувани); 2.3% според [1].
Intensive Care Units (ICU)
However, chloroquine is amongst the few Zn2+ ionophores [6]. Others include zinc pyrithione, zinc dimethyldithiocarbamate (Ziram)
and clioquinol [7]. The latter being a potential alternative to chloroquine. Ionophores are facilitators of ion transport across the cellular
Next, it is realized that Zn2+ inhibits coronavirus RNA polymerase activity in cell culture provided it is effectively heralded into the
intracellular milieu, that is zinc ionophores block the replication of the virus [8].
Now we are in position to raise the following hypothesis: Zn-deficit (in all its aspects) is the major cause of the COVID-19 associated
high C.F.R.
Suppose, this is indeed the most likely reason for the immune system dysfunction, than it should be able to explain the rest of the
Let us begin:
Observables 2, 3 & 5 are exhausted by the statement that COVID-19 is characterized by progressively increasing C.F.R. as a
function of the age and are explained away by Zn-deficiency being age related [9]: The serum Zn concentration is correlated
inversely with age (r=-0.11, p=0.018). Note, the age-dependent deficiency is not necessarily dietary dependent but is rather
an absorption issue.
Zn-deficiency and anemia are gender related [9]: The serum Zn concentration is 77.4 +/- 9.7
microg/dL in men and 79.1 +/- 10.4 microg/dL in women (p= 0.09). Anemia (A) diagnosed by the World Health
Organization criteria is present in 17.3% of men and in 13.5% of women - Amen/Awomen = 1.28, while Covid-19 associated = 1.65 which is close enough (28%) to explain Observable 4.
Observable 6, that is COVID-19 associated C.F.R. increases with the presence of comorbidities, can be explained away by
the chronic condition induced Zn-deficiency in cancer (5.6% COVID-19 C.F.R.) and diabetes (7.3% COVID-19 C.F.R.)
sufferers. The rest of the relevant comorbidities generally reduce survivability in acute inflammatory instances.
Zn is also the only variable associated with anemia risk [10] and is correlated with hemoglobin concentration [9], that is
hemoglobin concentration can be used to infer Zn-deficiency. The serum Zn concentration is significantly lower in patients
with anemia than in those without anemia. Note, Observable 7 points to complications due to COVID-19 being associated
with hemoglobin concentration being in the lower end (or below) of the range for the average healthy individual, which we
interpret as an indication of Zn-deficiency.
In conclusion, we would like to turn the attention towards the 1+ billion people worldwide, who are Zn-deficient [11] and therefore at
risk with respect to COVID-19 associated complications. The three major causes of Zn- deficiency are 1.) dietary vegeratians at
highest risk; 2.) poor absorption elderly or suffering from acrodermatitis enteropathica; 3.) chronic conditions: alcohol addiction,
cancer, diabetes, ect. The present hypothesis represents a falsifiable statement. If proven correct, improvement in the zinc dietary
intake and zinc cellular absorption (via Zn2+ ionophores for the elderly) can lay the foundation for a doable and strong SARS-CoV-2
viral counter-measure and greatly reduce COVID-19 associated C.F.R., therefore reduce the need for draconian social distancing
which vastly damages world economy.
Текст на български език /Bulgarian lang. text
Наблюдаемите, свързани с COVID-19 включват [1]:
1. 80,9% от хората ще преболедуват SARS-CoV-2 вирусната инфекция (и болестта COVID-19) с лека или никаква
2. COVID-19 е мека, ако изобщо присъства при деца под 9 години (0% С.С.).
3. COVID-19 се проявява с прогресивно увеличаваща се С.С. като функция на възрастта (10-39г 0,2%; 40-49г 0,4%;
50-59г 1,3%; 60-69г 3,6%; 70-79г 8% и > 80г 14,8%).
4. COVID-19, обвързаната C.С. зависи от пола с уклон към мъжете. Мъжката C.С. от 2,8% и е значително по-висока
от 1,7% при жените.
5. COVID-19, обвързаната C.С. доминира в окупационната група на пенсионерите 5,1%.
6. COVID-19, обвързаната C.С. нараства с наличието на съпътстващи заболявания: сърдечно-съдови 10,5%; диабет
7,3%; хронични респираторни / хипертония 6%; рак 5,6%.
7. Средната концентрация на хемоглобина (в g / L) при пациентите, които се нуждаят от интензивно лечение, е 122,
докато при пациентите, които не се нуждаят от интензивно лечение, е 130,5 с малка статистическа значимост (p =
0,2) [2].
Първото наблюдаемо е от ключово значение за побеждаването на паниката порoдена от липсата на ваксина и/или
специфична вирусна химиотерапия, тоест идентифицирането (и одобрението) на малка молекула, способна да а.) инхибира
репликацията на вируса; б.) постигане терапевтични концентрации в засегнатите тъкани (белите дробове, сърцето, червата)
ин виво и в.) която не е токсична.
Първото наблюдаемо е доказателство, че имунната система на човека е перфектно оборудвана за справяне с вируса,
следователно степента на смъртност от болестта се корени главно в неправилното функциониране на имунната система.
Естествено, ние поставяме въпроса: Коя е най-вероятната причина за дисфункцията на имунната система , и която води до
не-пренебрежима С.С. свързана с COVID-19 и е в състояние да обясни останалата част от наблюдаемите като очевидни?
За да се достигне до отговор на въпроса, излагаме хипотеза на базата на препоръчаното китайско лечение с хлороквин [3,4].
Почти универсалното анти-вирусно действие на хлороквина (инхибитор на ендозомното подкисляване) е свързано главно с
инхибиране на pH-зависимите етапи на вирусната репликация [5].
Хлороквинът обаче е сред малкото Zn2+ йонофори [6]. Други подобни молекули включват цинк пиритион (zinc pyrithione),
цинк диметилдитиокарбамат (zinc dimethyldithiocarbamate (Ziram)) и клиоквинол (clioquinol) [7]. Последният е потенциална
алтернатива на хлороквина. Йонофорите са молекули улесняващи транспортирането на йони през клетъчната мембрана.
По-нататък, показано е, че Zn2+ инхибира активността на коронавирусната РНК полимераза в клетъчна култура, при условие
че е ефективно въведена във вътрешноклетъчната среда, тоест цинковите йонофори блокират репликацията на вируса [8].
Сега сме в състояние да изкажем следната хипотеза: Дефицитът на цинк (във всичките му аспекти) е основната причина за
свързаната със COVID-19 висока степен на смъртност.
Да предположим, че това наистина е най-вероятната причина за дисфункцията на имунната система, тогава трябва да можем
да обясни останалата част от наблюдаемите като очевидни.
Нека започнем:
Наблюдаеми 2, 3 и 5 се изчерпват с твърдението, че COVID-19 се характеризира с прогресивно увеличавaща се C.С.
като функция на възрастта и се обясняват с това, че дефицитът на цинк е свързан с възрастта [9]: Серумната
концентрация на цинк е анти-корелирана с възрастта (r = -0,1, p = 0,02). Забележете, възрастово обусловеният
дефицит на цинк не е непременно свързан с хранителния режим, а е по-скоро въпрос на затруднено усвояване.
Дефицитът на цинк и анемията са свързани с пола [9]: Серумната концентрация на цинк е 77,4 +/- 9,7 microg/dL при
мъжете и 79,1 +/- 10,4 microg/dL при жените (p = 0,09). Анемията (A), диагностицирана по критериите на Световната
здравна организация, е налична при 17,3% от мъжете и при 13,5% от жените, т.е. отношението - A мъже / A жени = 1,28,
докато С,С.мъже/С.С.жени=1,65 свързана с Covid-19, е достатъчно близо (28%), за да се обясни Наблюдаемо 4.
Наблюдаемо 6, което е свързано със увеличаваща се с наличието на придружаващи заболявания С.С. при COVID-19,
може да се обясни със хроничния цинков дефицит на страдащите от рак (5,6% С.С. при COVID-19) и диабет (7,3%
С.С. при COVID-19). Останалите от значимите съпътстващите заболявания са стандартно свързани с редукция на
преживяемостта при остри възпалителни заболявания.
Концентрацията на цинк е и единствената променлива, свързана с риска от анемия [10] и определя концентрацията
на хемоглобин [9], тоест концентрацията на хемоглобин може да се използва за установяване на дефицит на цинк.
Серумната концентрация на цинк е значително по-ниска при пациенти с анемия, отколкото при тези без анемия.
Забележете, Наблюдаемо 7 сочи, че усложненията при COVID-19 се дължат на това, че концентрацията на
хемоглобин при страдащите е в долния край (или под) диапазона за средно статистическия здрав индивид, което ние
интерпретираме като индикация за дефицит на цинк.
В заключение, бихме искали да обърнем внимание на това, че 1+ милиарда души по света, страдат от дефицит на цинк [11] и
следователно са изложени на риск от усложнения, свързани с COVID-19. Трите основни причини за недостиг на цинк са: 1.
хранителен режим - вегетарианци са с най-висок риск; 2.) лоша абсорбция - възрастните хора или страдащите от
акродерматит ентеропатика; 3.) хронични състояния: алкохолна зависимост, рак, диабет и др. Настоящата хипотеза
представлява фалшифицируемо твърдение, т.е. може да бъде подложена на проверка. Ако се окаже правилна, подобряването
на приема на цинк в хранителния режим и клетъчната абсорбция на цинк (чрез Zn2+ йонофори за възрастните хора) може да
постави основата за изпълнимо и силно противодействие на вируса SARS-CoV-2 и значително да намали свързаната с
COVID-19 степен на смъртност, като по този начин доведе до отпадане на нуждата от драконовски мерки за социална
изолация – силно увреждаща световната икономика.
[1] Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. [The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus
Diseases (COVID-19) in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020; 41(2):145151. DOI:10.3760/cma.j.issn.0254-6450.2020.02.003.
[2] Chaolin Huang,, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, the Lancet,395, p497 (2020)
[3] Jianjun Gao, Zhenxue Tian, Xu Yang, Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in
clinical studies, BioScience Trends, 2020, Volume 14, Issue 1, Pages 72-73, Released March 16, 2020, [Advance publication] Released February 19, 2020, Online
ISSN 1881-7823, Print ISSN 1881-7815,
[4] Wang, M., Cao, R., Zhang, L. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269
271 (2020).
[5] A. Savarino, J. R. Boelaert, A. Cassone, G. Majori, R. Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases, The Lancet, 3, p722
[6] Xue J, Moyer A, Peng B, Wu J, Hannafon BN, et al. (2014) Chloroquine Is a Zinc Ionophore, PLoS ONE 9(10): e109180. doi:10.1371/journal.pone.0109180
[7] Ding, W.‐Q. and Lind, S.E. (2009), Metal ionophores – An emerging class of anticancer drugs, IUBMB Life, 61: 1013-1018. doi:10.1002/iub.253
[8] te Velthuis AJW, van den Worm SHE, Sims AC, Baric RS, Snijder EJ, et al. (2010) Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro
and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLoS Pathog 6(11): e1001176. doi:10.1371/journal.ppat.1001176
[9] Idei M, Miyake K, Horiuchi Y, et al. [Serum zinc concentration decreases with age and is associated with anemia in middle-aged and elderly people]. Rinsho byori.
The Japanese Journal of Clinical Pathology. 2010 Mar; 58(3):205-210. PMID: 20408437 40 years course study!
[10] Lisa A Houghton, Winsome R Parnell, Christine D Thomson, Timothy J Green, Rosalind S Gibson, Serum Zinc Is a Major Predictor of Anemia and Mediates the
Effect of Selenium on Hemoglobin in School-Aged Children in a Nationally Representative Survey in New Zealand, The Journal of Nutrition, Volume 146, Issue 9,
September 2016, Pages 16701676,
[11] Kumssa, D., Joy, E., Ander, E. et al. Dietary calcium and zinc deficiency risks are decreasing but remain prevalent. Sci Rep 5, 10974 (2015).
... Роль цинка в функционировании организма и, в частности, иммунной и дыхательной системы, не подлежит сомнению [27,28]. В статье [29] показаны достаточно устойчивые корреляции между развивающимися при COVID-19 осложнениями и уровнем цинка в тканях и жидкостях. В то же время в ряде публикаций приводятся опровергающие это утверждение данные [30,31] Применение нашей разработки как средства против SARS-CoV-2 при введении композиции ингаляционным способом после ее нанесения на поверхности обычной медицинской маски оказалось достаточно эффективным, что было установлено предварительными исследованиями на добровольцах. ...
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Background: Zinc, selenium, and vitamin D status of New Zealand (NZ) school-aged children was examined in a national survey in 2002. To our knowledge, however, the role of these micronutrients as predictors of hemoglobin has not been explored despite plausible mechanisms for such relations. Objective: We examined the relations of iron, zinc, selenium, and vitamin D status with hemoglobin and anemia in children of New Zealand European and other (NZEO) ethnicity enrolled in the 2002 Children's Nutrition Survey and explored whether zinc mediated the relation between selenium and hemoglobin. Methods: Multivariate regression was performed to examine the relations of serum micronutrient biomarkers, acute inflammation, socioeconomic status, and body mass index (BMI) with hemoglobin and anemia of NZEO children aged 5-15 y (n = 503). A mediation analysis also investigated direct and indirect (through zinc) relations between selenium and hemoglobin. Results: In total, 4.6% of the children were anemic, 3.2% had depleted iron stores, and none had iron deficiency anemia. The prevalence of low serum zinc (<8.7-10.1 μmol/L depending on age and sex), selenium (<0.82 μmol/L), and 25-hydroxyvitamin D (<50 nmol/L) was 14.1%, 22.9%, and 48.5%, respectively. Major predictors of hemoglobin were serum zinc, age, and BMI-for-age z score (P < 0.001); log ferritin and being female were also statistically significant (P < 0.05). Selenium had an indirect effect that was mediated by zinc, with a significant effect of selenium on zinc (P = 0.002) and zinc on hemoglobin (P < 0.001). Zinc was the only variable associated with anemia risk (OR: 5.49; 95% CI: 1.95, 15.46). Conclusions: Low serum zinc was an independent risk factor for anemia in NZEO school-aged children and mediated the effect of low selenium on hemoglobin. These findings emphasize the importance of considering multiple micronutrient deficiencies in addition to iron when interpreting anemia and of appreciating the mechanistic interactions that underlie these associations.
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lobally, more than 800 million people are undernourished while >2 billion people have one or more chronic micronutrient deficiencies (MNDs). More than 6% of global mortality and morbidity burdens are associated with undernourishment and MNDs. Here we show that, in 2011, 3.5 and 1.1 billion people were at risk of calcium (Ca) and zinc (Zn) deficiency respectively due to inadequate dietary supply. The global mean dietary supply of Ca and Zn in 2011 was 684 ± 211 and 16 ± 3 mg capita−1 d−1 (±SD) respectively. Between 1992 and 2011, global risk of deficiency of Ca and Zn decreased from 76 to 51%, and 22 to 16%, respectively. Approximately 90% of those at risk of Ca and Zn deficiency in 2011 were in Africa and Asia. To our knowledge, these are the first global estimates of dietary Ca deficiency risks based on food supply. We conclude that continuing to reduce Ca and Zn deficiency risks through dietary diversification and food and agricultural interventions including fortification, crop breeding and use of micronutrient fertilisers will remain a significant challenge.
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Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.
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Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference with viral polyprotein processing. In this study we demonstrate that the combination of Zn(2+) and PT at low concentrations (2 µM Zn(2+) and 2 µM PT) inhibits the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture. The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC). Using an activity assay for RTCs isolated from cells infected with SARS-CoV or EAV--thus eliminating the need for PT to transport Zn(2+) across the plasma membrane--we show that Zn(2+) efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses. Enzymatic studies using recombinant RdRps (SARS-CoV nsp12 and EAV nsp9) purified from E. coli subsequently revealed that Zn(2+) directly inhibited the in vitro activity of both nidovirus polymerases. More specifically, Zn(2+) was found to block the initiation step of EAV RNA synthesis, whereas in the case of the SARS-CoV RdRp elongation was inhibited and template binding reduced. By chelating Zn(2+) with MgEDTA, the inhibitory effect of the divalent cation could be reversed, which provides a novel experimental tool for in vitro studies of the molecular details of nidovirus replication and transcription.
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Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Its best-studied effects are those against HIV replication, which are being tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of tumour necrosis factor alpha and interleukin 6, which mediate the inflammatory complications of several viral diseases. We review the available information on the effects of chloroquine on viral infections, raising the question of whether this old drug may experience a revival in the clinical management of viral diseases such as AIDS and severe acute respiratory syndrome, which afflict mankind in the era of globalisation.
The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China for treatment of COVID-19 infection in larger populations in the future.
Zinc (Zn) is an essential trace element for humans and its deficiency can lead to several clinical problems. This study examined the relationship between the serum zinc concentration and anemia in middle-aged and elderly people. Samples were obtained from 150 men and 303 women who received health checkups over the course of 40 years. The serum concentration of Zn was measured as well as the complete blood count (CBC), alanine aminotransferase (AST), aspartate aminotransferase (ALT), gamma-glutamyl transferase (gamma GT), total cholesterol (TC), high density lipoprotein (HDL-C), triglyceride (TG), creatinine (Cr), uric acid (UA) and fasting plasma glucose (FPG). The serum Zn concentration was 77.4 +/- 9.7 microg/dL in men and 79.1 +/- 10.4 microg/dL in women (p= 0.09). The serum Zn concentration correlated inversely with age (r=-0.11, p=0.018). Anemia diagnosed by the World Health Organization criteria, was present in 17.3% of men and in 13.5% of women. However, more than 80% of the anemia was normocytic (men 86%, women 81%). The serum Zn concentration was significantly lower in those with anemia than in those without anemia. The Hb level correlated with the serum Zn concentration (men r=0.25, p=0.002, women r=0.23, p<0.001). A multiple regression analysis confirmed a low serum Zn concentration to be associated with a low Hb level. In conclusion, this study indicates that the serum Zn concentration decreases with age and that a low Zn concentration is associated with normocytic anemia, thus suggesting that a Zn deficiency may therefore be one of the causes of anemia in elderly people.
Compounds that bind metals such as copper and zinc have many biological activities, including the ability to induce apoptosis in cancer cells. Although some of these compounds have been considered to act as chelators of metals, decreasing their bioavailability, others increase intracellular metal concentrations. We review recent work regarding the recognition of the biological effects of metal ionophores with different structures, particularly with regard to their actions upon cancer cells focusing on dithiocarbamates, pyrithione, and the 8-hydroxyquinoline derivative, clioquinol. We provide a biologically based classification of metal-binding compounds that allows an experimental distinction between chelators and ionophores that can be readily used by biologists, which may lead to further study and classification of metal-binding drugs. Metal ionophores may kill cancer cells by a number of mechanisms, including lysosomal disruption and proteasome inhibition, and likely others. Because some of these compounds have been safely administered to animals and humans, they have the potential to become clinically useful anticancer agents.
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, the Lancet
  • Chaolin Huang
Chaolin Huang,, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, the Lancet,395, p497 (2020) S0140-6736(20)30183-5