Published: 2020.04.23
Updated: 2020.04.26 – revision of serum zinc, addition of serum selenium
Updated: 2020.04.27 – widespread zinc deficiency in crops, list of countries
Updated: 2020.05.05 – revision of serum selenium
Updated: 2020.05.19 – gap between how USA and non-USA black people are affected
Updated: 2020.06.02 – serum zinc updates; Iran’s serum zinc levels increased in recent years after introducing zinc fertilizers
Using numbers from https://www.worldometers.info/coronavirus/ from Sunday, 2020.04.12.
These numbers are highly dependent on the number of tests done, on how much each country is willing to report, on how it counts the deaths, on how close the contact is in some countries as opposed to others, but the numbers still indicate there are more factors influencing the gaps between countries, especially gaps between countries of the same region like Scandinavia or the Iberian Peninsula. And now the analysis can be made on very big numbers.
Limitations: death rate computed as total deaths/total cases is not a precise world indicator as long as the infection peak is not reached yet in some parts of the world.
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1) GENETICS
Scientists observe that the COVID-19 caused mortality decreases as the frequency of the ACE D allele increases. According to their databases, the frequency of the ACE D allele appears to be increased in Eastern Europe, Balkans, Middle East.
„Not only has ACE2 facilitated the invasion of SARS virus for rapid replication, but also ACE2 is depleted from the cell membrane and therefore the damaging effects of Ang II are enhanced, resulting in acute deterioration of lung”
“The D allele is associated with a reduced expression of ACE2”
“prevalence of COVID-19 infections inversely correlates with the ACE D allele frequency”
https://europepmc.org/article/pmc/pmc7102561
http://pdfs.semanticscholar.org/9280/84a3d33266b31121ff674f4645154476b405.pdf
UPDATE 2020.05.19: Black populations probably have higher frequency of the ACE D allele and all black populations from Africa and the American continents (including Jamaica, Haiti, Barbados, Bahamas, Antigua and Barbuda, Montserrat, Anguilla, Grenada, Saint Lucia, Virgin Islands, Martinique, etc) appear to have low virus spreading and low COVID-19 caused mortality except for the ones in the USA which are badly affected. Maybe there are some environmental factors in the USA which are aggravating for people with this genetic makeup? Note that non-USA blacks probably access less healthcare and may be more crowded in the big African cities and they are still doing better now.
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2) POLLUTION
Northern Italy has been very polluted and it is the most affected region: „the mortality rate is up to 12% in the northern part of Italy, while it is only approx. 4.5% in the rest of the country… The two northern Italian regions are among the most air-polluted regions in Europe.”
https://www.sciencedaily.com/releases/2020/04/200406100824.htm
New York is hit harder than other states in the USA. Coincidence: „Air pollution is killing New Yorkers”
https://nypost.com/2020/02/13/air-pollution-is-killing-new-yorkers-but-its-not-coming-from-here/
Mexico had a big increase in cases and death rate numbers towards the end of April (but total tests/total cases is too small for accuracy). Coincidence: “‘Just leave’: Delhi, Beijing and Mexico City residents on how to cope with pollution“
UK – 12.5%. Coincidence: „London, the Midlands and the north-west had the highest levels of nitrogen oxides and higher numbers of coronavirus deaths… Previous research showed air pollution increased deaths during the Sars outbreak in 2003, and long-term exposure to dirty air is well known to damage lung health… Our study adds to growing evidence from northern Italy and the US that high levels of air pollution are linked to deadlier cases,”
France – 10.57%. Coincidence: „In recent years, the European Commission has repeatedly criticized France for not respecting EU air quality norms and last year took France to the European Court of Justice.”
Netherlands 10.83% & Belgium 11.94%. Coincidence: satellite images show high nitrogen dioxide pollution over northern Belgium, western Netherlands and other areas affected by COVID-19 including Madrid, Barcelona, London, Paris, Brussels, western Germany, Milan and Moscow.
Pollution map for nitrogen dioxide (world view and Europe view from 2018):
Also, check out the connection between pollution and selenium at point 5.
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3) THE SUN (LATITUDE)
The sun is my favorite; we have a close relationship and we see each other often considering how much I suffered in its 45 days absence a few winters ago. „You cannot exhaust your vitamin D reserves in a month.” But what if these reserves were too low to begin with which also happens frequently to old people who are now isolated? And what if you keep them isolated even more?
And the benefits of the sun probably extend far beyond vitamin D.
Seeing the gap between Spain-Italy and Scandinavia, I thought initially that the sun was not a significant factor. Then I remembered the southern hemisphere: those people have just ended their summer with enhanced reserves and immune system, so table 1 does justice to the sun and emphasizes its importance:
- All countries south of parallel 10 have lower death rate
- All countries with high death rate (>8.7%) are in the northern hemisphere to the north of parallel 40
UPDATE 2020.05.26: Sunny Brazil, Ecuador and even Mexico appear to have higher death rates today (6.2%, 8.5%, 10.7%), but the total tests/total cases ratio is too small for accuracy (1.94, 2.85, 3.17). More testing should identify more people with lighter symptoms and higher survival rate. For example, this ratio is 180.6 in Australia and 721(!) in Venezuela, so the numbers should be much more accurate in these cases.
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4) ZINC
“Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973827/
“New research suggests that zinc helps control infections by gently tapping the brakes on the immune response in a way that prevents out-of-control inflammation that can be damaging and even deadly… our work is focused on what happens once you get an infection — if you are deficient in zinc you are at a disadvantage because your defense system is amplified, and inappropriately so”
https://www.sciencedaily.com/releases/2013/02/130207131344.htm
James A. Robb, “University of Colorado School of Medicine MD, a pathologist, and molecular virologist”: “In my experience as a virologist and pathologist, zinc will inhibit the replication of many viruses, including coronaviruses. I expect COVID-19 will be inhibited similarly, but I have no direct experimental support for this claim. I must add, however, that using zinc lozenges as directed by the manufacturer is no guarantee against being infected by the virus, even if it inhibits the viral replication in the nasopharynx.”
https://www.uchealth.org/today/zinc-could-help-diminish-extent-of-covid-19/
Gathering zinc numbers began with Italy 13.39 vs Austria 24.9, but then it seemed to reach a dead end because there are many factors which raise or lower serum zinc levels and which could hide very complex issues.
A French study from 2010 involving 12374 persons who were not supplementing made some interesting remarks:
- “Linear trends observed in women but not in men showed decreasing serum zinc concentration with education” – could this mean that intense intellectual activity uses more zinc especially in women and that these persons could benefit more from a zinc supplement?
- “Serum zinc concentration was significantly lower in women who did not take contraceptive pills” + “The higher serum zinc concentration in heavy female smokers compared with never and former smokers was unexpected although this observation was in agreement with some previous reports” + “The higher serum zinc concentrations in menopausal women than in non-menopausal women” show that serum zinc could be higher in less desirable situations also and could indicate processes which are not optimal anymore. Could these 3 factors impair the mobilization of vitamin A stores from the liver and thus lead to less zinc required for RBP (Retinol Binding Protein) and more zinc available in the blood?
- “Age was negatively associated with serum zinc only in men” – zinc absorption decreases with age, but is it possible that point 2) compensates for this tendency in women?
https://www.nature.com/articles/ejcn2010118
Lower zinc levels are observed with some diseases in the studies while higher zinc levels are observed with other diseases.
Seasonal variations of serum zinc were also observed “with the lowest and highest levels found in October and August (98.5 vs. 122.7)”:
And is it possible that an (acetate or gluconate) zinc supplement dissolved in the mouth could have more effect on the airways and coronaviruses (as the above and below studies imply) and less effect on serum zinc levels?
https://www.ncbi.nlm.nih.gov/pubmed/28515951
Unfortunately, zinc numbers from a few countries come from specific age groups. Although some adjustments were made, these numbers are subject to variations due to the reasons mentioned above, but the extremes are still powerful (as they can make up for these variations), especially the high zinc extreme (>15umol/l) which means Czech Republic, Portugal, Iran, Norway, Canada, South Korea, Pakistan and Austria – all with lower DR regardless of continent, latitude and approach. (Table 4)
UPDATE 2020.06.02: Iran noted zinc deficiency in 2005, but in recent years its serum zinc levels increased, often >100ug/dL after introducing zinc fertilizers. Unlike other countries like Canada which had an unexpected DR rise to ~8% today (what could be so aggravating there?), Iran’s DR is lower today (5%) than in the initial sampling (6.22%):
http://www.fao.org/tempref/agl/agll/docs/fertuseiran.pdf
The green numbers made me wonder: soils or genetics? Maybe gene expression is influenced by soil properties?
Findings of the following book from 2008 highlight some more coincidences:
The world map at page 109 suggests zinc deficiency in crops is widespread in South America (Brazil, Peru, Ecuador, Colombia, Venezuela), Mexico, most of Africa, Asia (most of Middle East, China, India). Note that Pakistan and Iran are using Zn fertilizers which could explain their high reported serum zinc levels.
In Europe, the book notes medium deficiency in Spain, Italy, France, Switzerland, Netherlands, Greece, parts of Germany without a wish to use zinc fertilizers.
More notes under the chapter about USA: “It has been found that the increased use of the herbicide glyphosate in intensive arable production, including with “glyphosate-tolerant” GM crops, can have an effect on the availability of micro-nutrients such as zinc, manganese and others to crops and may therefore necessitate increased applications of zinc fertilisers to overcome this problem… It is widely recognised that zinc deficiency becomes more prevalent with increasing intensity of cropping… In addition, these higher yielding crop varieties are often zinc-inefficient in comparison with the previously grown locally-adapted varieties”.
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5) SELENIUM
“Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses.”
https://www.mdpi.com/2072-6643/11/9/2101
“Selenium deficiency creates a weakening of the defense against infectious diseases by reducing selenoprotein expression. However, nutritional status of the host can also lead to viral genome mutations from a benign or mildly pathogenic virus to a highly virulent one under oxidative stress that could further spread in hosts with adequate selenium intake.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769590/
“When Se-deficient virus-infected hosts were supplemented with dietary Se, viral mutation rates diminished and immunocompetence improved.”
https://link.springer.com/article/10.1007%2Fs12011-011-8977-1
Se in measles patients was found to be almost half of the Se in healthy people: “The mean of selenium concentration was significantly lower in the patients [with measles] than in the controls (46.4±14.1μg/L versus 86.5±13.9μg/L, P<0.0001)“
https://www.ncbi.nlm.nih.gov/pubmed/28447938
Etc.
I found numbers on the estimated daily intake for several countries, sometimes numbers on serum selenium; some seem reliable, some less, some conflicting; about some countries it is mentioned that they fertilize with Se (Finland, New Zealand), about others it is not so clear although they are studying it and maybe they have implemented it (Czechia had very low levels and did several studies on Se soil fertilizing). There are also exceptions from the general trend (Croatia), but, overall, these numbers show a big coincidence.
The following were deleted from the table:
- Countries without Se numbers,
- Countries with the number of tests below 300/1M and countries with less than 1000 cases for more relevance,
- China which has both excess and low Se areas – Hubei seems to be a low Se region (also polluted)
Note: Se intake equivalent is estimated as follows:
- Mean if interval is given
- If only serum Se is available, then it is compared to other countries and a lower intake value is chosen
- If there are only remarks about high Se soils, then value 50 was chosen to be below the RDA of 55 for a lower weight than the confirmed cases
Table 3 – conclusions while observing the extremes:
- Top 7 countries by deaths/infected (>8.7%) appear to have lower Se intakes: Italy, UK, Belgium, Netherlands, France, Spain and Sweden;
- All countries with higher Se intakes have lower death rate: Switzerland 4%, USA 3.8%, Canada 2.5%, while the others are below 2%: S. Korea, Norway, Finland, Japan, Australia, Iceland, Singapore, New Zealand;
- With a lower weight, we can also take into consideration the countries with remarks about high Se soils: Chile, Peru, Israel, Colombia, Ireland.
Notice that all countries with higher selenium intake have lower death rates regardless of genetics, continent, latitude or the level of monitoring, control and restrictions applied to the population.
UPDATE 2020.05.28: Venezuela is the country with the highest known Se intakes without observing toxicity: 200-350ug/day. Virus spreading is low, DR is very low at 0.88% and testing is extensive (highest number of tests/1M population in South America, tests/cases ratio is 721!), so the numbers should be accurate and may indicate high Se protection against this novel coronavirus.
UPDATE 2020.04.26: more data gathered on serum selenium. The above are confirmed with a few exceptions: Ireland seems to have lower level while Greece, Portugal and Iceland appear to have higher levels.
Table 5 – similar conclusions:
- All countries with high death rate (>8.7%) have lower serum selenium (Netherlands was removed due to unclear and conflicting data)
- All countries with higher serum selenium levels (>92) have lower death rate: Switzerland 4.08%, USA 3.89%, while the others are below 3%: Finland, Portugal, Australia, S.Korea, Iceland, Norway, Singapore, Japan, Canada.
Again: all countries with high reported serum selenium have lower death rate regardless of genetics, latitude, continent or the level of monitoring, control and restrictions applied to the population.
Note1: USA has high Se levels overall, but the DR is higher compared to countries with similar Se levels which may mean that more aggravating factors are at play here.
Note2: Studies find that serum Se interval 92-122 ug/l is associated with decreasing risk of diabetes while very high selenium levels (>142ug/l) are associated with higher risk of diabetes:
https://nutritionj.biomedcentral.com/articles/10.1186/s12937-016-0169-6
But Canada, Japan and Venezuela have much lower diabetes rates than the US in spite of having much higher selenium levels, often >142ug/l. So, again, maybe more aggravating factors are at play in the US. For example, sugar consumption per capita in the US was at least 42% higher than in Canada, Japan and Venezuela in 2015.
https://www.statista.com/statistics/535219/global-sugar-per-capita-consumption-by-country/
Maybe higher selenium should be accompanied by higher chromium for better control of blood sugar. Maybe the extra selenium intensifies some processes which also require more chromium thus leaving less available chromium for other activities?
The Scandinavian gap. Coincidence:
“During the late 1970s and early 1980s … The average Se intake in Norway at that time was high enough… about 70–80 μg/day, but the average Se intake in Finland fell well below the American recommendations, being only about 30 μg/day… and the situation in Sweden was – and is – not much better. Because of concern that low Se intake might be an important contributory cause of high cardiovascular mortality, it was decided in Finland to start fertilization with Se... However, the Swedish health authorities did not want to do the same.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556185/
Current numbers:
- Sweden: 8.74%
- Finland: 1.69%
- Norway: 1.79%
Also, pollution mentioned at point 2 reduces the selenium availability even more. About mercury:
“In addition to stealing available selenium from selenoprotein synthesis, methylmercury can also bind to the selenium of the selenocysteine in the selenoprotein. Mercury is, therefore, biochemically defined as a “highly specific, irreversible selenoenzyme inhibitor.”
http://net-effects.und.edu/pdfs/Selenium-Mercury.pdf
Other toxic substances: “Selenium (Se) has been shown to counteract the toxicity of heavy metals such as cadmium, inorganic mercury, methylmercury, thallium… Se appears effective in counteracting the chemical carcinogens (3-methyl-4-dimethyl-aminoazobenzene, 2-acetylaminofluorene, diethylnitrosamine, aflatoxin, 7,12-dimethylben (a) anthracene, benzopyrene and 3-methylcholanthrene)“
https://www.ncbi.nlm.nih.gov/pubmed/1304229
The researchers’ conclusions almost 20 years ago are like a prophecy come true:
„Mounting evidence suggests that chronic marginal Se intake increases susceptibility to viral infection and viral disease sequelae, cancer, cardiovascular diseases, thyroid dysfunction and various inflammatory conditions. Se’s anti-viral activity is of particular interest, given the high global prevalence of severe viral infections, including HIV/AIDS, influenza, hepatitis B and hepatitis C. In a Se-deficient host the benign coxsackie virus becomes cardiomyopathic, influenza viruses cause more serious lung pathology and HIV infection progresses more rapidly to AIDS.” (Graham H Lyons, University of Adelaide, Australia, 2004)
“It is thus a matter of urgency that many countries begin to address this major public health issue and develop effective, sustainable ways to increase Se intakes” (G.F. Combs, 2001)
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The above coincidences applied to some cases:
Norway 1.79%:
- Pluses: selenium, zinc, low pollution
- Minuses: insufficient sun exposure
Sweden 8.74%:
- Pluses: low pollution
- Minuses: insufficient sun exposure, low selenium
Australia 0.89%:
- Pluses: selenium, full sun
- Minuses: some polluted regions
Japan 1.65%:
- Pluses: high selenium
- Minuses: NO2 pollution, oldest population (many say that Italy has old population, but Japan is ahead and still doing ok in the coronavirus statistics)
Iceland 0.41%:
- Pluses: selenium, low pollution, many tests/1M
- Minuses: insufficient sun exposure
Italy 12.77%:
- Pluses: –
- Minuses: heavy NO2 pollution in the north may make the difference if the rest of the country is at 4.5%, apparently baseline selenium&zinc, selenium may be lowered by pollution
South Korea 2%:
- Pluses: zinc, selenium
- Minuses: NO2 pollution
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Of course, there are more factors contributing to these numbers and it would be useful if more research went in these directions to gain more knowledge about lowering susceptibility to coronaviruses and to find out how we can honor and support our health in reaching its optimum.
3 out of 5 factors explored here are highly controllable.
The 4th – sun exposure – is sadly limited by quarantine restrictions although the sun is getting closer to the badly affected countries.
So, if we turned these factors to our advantage, could we reduce this coronavirus caused disease to a light cold or even less? As for many people it already goes by unnoticed.
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More resources:
https://www.frontiersin.org/articles/10.3389/fpls.2015.00136/full