HOW TO PREVENT DEVELOPMENT OF SEVERE COVID-19 DISEASE

Jun 6, 2020
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HOW TO PREVENT DEVELOPMENT OF SEVERE COVID-19 DISEASE


Evidence suggests that targeting innate lymphoid cells (ILCs) may be beneficial in the design of therapeutics for COVID-19 generated autoimmune disorders. As ILCs and T cells have many redundant functions, targeting and neutralizing their effector cytokines might be a better option. Alternatively, targeting their upstream activating mediators (IL-23, IL-1B, or IL-6), or their survival factors (IL-7) could be used as an approach to treat inflammatory diseases.

The epithelium comprises a physical barrier, which together with the mucus layer and production of anti-microbial peptides provides a containment barrier, which confines microbes in the lumen. The innate lymphoid cells residing in the immune compartment of the lamina propria, which is a thin layer of connective tissue that forms part of the moist linings known as mucous membranes or mucosa, which line various tubes in the body, such as the respiratory tract, the gastrointestinal tract, and the urogenital tract, are key early warning sentinels detecting invading pathogens through conserved pattern recognition receptors, such as toll-like receptors. Pathogen detecting populations, include cells of the mononuclear phagocyte system, including macrophages and dendritic cells (DCs), which engulf and process microbial antigens and present the antigens to adaptive immune cells, thus providing initial signals to adaptive immune system lymphocytes to engage potent antigen-specific T and B cell responses.

Innate lymphoid cells (ILCs) are distributed throughout the human body in lymphoid and non-lymphoid tissues, but are especially enriched at the mucosal barrier surfaces, where they directly interact with a number of different cell types; hematopoietic or other . ILCs have lymphoid-like morphology, but lack any antigen-specific receptors. Arising from a common lymphoid progenitor and similarly to T cells, they can be further subdivided into phenotypically and functionally distinct populations that produce different combinations of effector cytokines to mediate their functions. Their development depends on different transcription factors, which are also used to help divide ILCs into 5 main groups; group 1 ILCs that includes Natural Killer cells, as well as the non-cytotoxic ILC1s, group 2 ILCs or ILC2s, group 3 ILCs including ILC3s, group 4 containing lymphoid tissue inducer (LTi) cells and, group 5 are regulatory ILCs or ILCregs.

The production of Interleukin-5 (IL-5) by ILC2s in the lung leads to eosinophil recruitment, and other cell populations interact and shape the presence of lung ILC2s in airway inflammation. In addition, they also promote proliferation of B cells. It seems, that the increase in ILC2s present correlates with the severity of inflammation in the lungs, intestines, kidneys and other organs of patients suffering from severe COVID-19, and evidence confirms some ‘immunogen- experienced’ ILC2s persist after the resolution of the initial inflammation, portraying similarities to memory T cells. So, people who have been previously exposed to other coronaviruses may carry some some "Immunogen-experienced" ILC2s in the in the immune compartment of their lamina propria, that can provide at least partial protection against SARS-CoV-2.

It has been shown in mice that Natural Killer cells (NK cells) and ILC1s inhibit ILC2 expansion due to the production of Interferon- Gamma, and therefore they (NK cells and non- cytotoxic group 1 Innate Lymphocyte Cells) may help prevent the development of severe COVID-19 disease.

I intend to support my thesis, that the primary obligatory weapon against SARS-COV-2 is our highly complex and ancient, innate immune system, and not the simple, modern adaptive immune system.


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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One of the reasons, why Caucasians are more susceptible to severe COVID-19 than East Asians:

Activation of the innate immune system is initiated by soluble pathogen pattern recognition molecules, which may be expressed on innate immune cells, bound to the extracellular matrix, or circulate in the blood as soluble molecules. One such soluble pathogen pattern recognition molecule is MBL (Mannose-Binding Lectin), which plays an important role in the body's immune response by attaching to foreign invaders such as bacteria, viruses, or yeast and turning on (activating) the complement system, which is one of the most important component of the innate immune system.

In the lung, MBL is found in the bronchial alveolar lavage of healthy individuals and also on the smooth muscle in airways following infection.

MBL deficiency can be caused by inherited gene defects, which have been identified in 5%–30% of the world population.

There are three coding region single nucleotide polymorphisms (SNPs) at codons 52, 54 and 57, termed the C, B, and D alleles respectively.

The frequency of these alleles varies depending on ethnicities. While all three alleles are observed in Caucasians, alleles C and D are very rare in East Asians.

Most MBL deficiency is due to the heterozygosity of these SNPs.


MBL-deficient hosts (those who contain C and D alleles also---the Caucasians) may present with systemic infection involving multiple organs, including blood (bacteremia), and uncontrolled inflammation due to cytokine storm (The major cause of death from COVID-19). Such infection and subsequent cytokine release may establish an autocrine loop which further escalate complications.


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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Aboriginal and Torres Strait Islander people, make up 30 per cent of the NT's population in Australia.

In the Northern Territory, Aboriginal people are often over-represented in the health system — but it's a different story for COVID-19, with official data indicating there have been no Aboriginal coronavirus patients in the NT to date.

Key points:

1) There have been just 30 confirmed cases of COVID-19 in the NT.

2) And, no community transmission.

AMSANT's John Paterson was "surprised" no Aboriginal people in the NT had
tested positive.

Conclusions:

1) Austronesian genes of this aboriginal population carry some Denisovan admixture, which protects them from catching and transmitting the virus.

2) Their 30% population in the Northern Territory, has given the whole territory, a herd immunity like effect.
I define, Pseudo Herd Immunity as a herd immunity like effect, seen at the level of total diverse population, which is due to the genetic grace of one of the member sub- population, that is different from the rest of the population by having an exclusive genetic difference, which is advantageous for saving the whole population from a communicable disease.

3) The ancestors of Austronesians were the Hunter gatherers, who bred and assimilated (or were assimilated by) the earlier Paleolithic Australo-Melanesian Negrito, Orang Asli, and Papuan populations in the islands at varying levels of admixture. They reached as far as Rapa Nui, Madagascar, and New Zealand at their furthest extent, possibly also reaching Canada and Greenland. Giving all the pre-existing populations at these places some Denisovan genes.

4) The Pseudo- herd immunity like effect, which we see in China, was due to secondary transfer of Denisovan genes attained by south China farmers, getting transferred to North upto Mongolia and northeast Russia, and west, Upto Tibet and Uzbekistan.
Directly by the mother population or through secondary crosses of the progeny populations. Some of which will be listed in my later posts regarding innate resistance of some human populations to COVID-19 disease at the individual as well as, population level (by virtue of they being, poor spreaders, of the disease).
 
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Jun 6, 2020
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Some Denisovan gene admixture in a population, protects it's members from Covid-19 caused severe illness and death. Members of these populations are also, less infective to others.
A good example are the indigenous people of Papua New Guinea.
Look at China.There the hunter gatherer populations crossed with farming populations 5000 to 10,000 years ago. This supplied a great chunk of their population with some Denisovan genes.
Now it looks, as if, China has already achieved some pseudo- herd immunity. Though only a negligible percentage of their 1.7 billion population got infected, and, with negligible number of deaths in ratio to their population.
The same is true for other ethnic populations of those south east asian countries, which were not additionally populated by later migrations of farming/trading communities from the middle east.
Example: Compare the infection and death rates of Indonesia and Papua New Guinea, which share borders.
Data:
https://en.wikipedia.org/wiki/Melanesians

Based on his genetic studies of the Denisova hominin, an ancient human species discovered in 2010, Svante Pääbo claims that ancient human ancestors of the Melanesians interbred in Asia with these humans. He has found that people of New Guinea share 4%–6% of their genome with the Denisovans, indicating this exchange.
 
Jun 6, 2020
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Indigenous Fijians made up only 56.8 percent of the population, 37.5 percent were Indian and the remaining groups including Chinese made up 5.7 percent.Apr 28, 2009

Different populations contain different amounts of Denisovan genes. This should be taken into account.

Hundreds of ethnic populations are there in Indonesia, some interacted for a longer time and more with austronesians and some, not at all. Depending on this, the distribution of Denisovan genes by the Austronesians took place.
Too mixed populations can confuse.
As on 15 May
There have only been
18 confirmed cases,
Out of which 15 have recovered and no deaths have occurred
in Fiji.
It is yet another example of Pseudo-Herd Immunity, bestowed on the total population by the aboriginal population.
Study shows COVID-19 vulnerability is highly dependent on host genetic architecture - https://www.news-medical.net/news/20200 ... cture.aspx

Humans and viruses have evolved together for millennia, resulting in genetic polymorphisms that guide the host responses to viral infection. Consequently, clinical variation in COVID-19 severity and symptomatic presentation may be a result of differences in host genetic factors related to the immune response.


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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https://www.washingtonpost.com/climate- ... ronavirus/

“When you look at the health disparities in Indian Country — high rates of diabetes, cancer, heart disease, asthma and then you combine that with the overcrowded housing situation where you have a lot of people in homes with an elder population who may be exposed or carriers — this could be like a wildfire on a reservation and get out of control in a heartbeat,” said Kevin Allis, chief executive of the National Congress of American Indians.


During the Spanish Flu:
Considering the conditions that made them vulnerable, the researchers said, “it is remarkable not that so many of them were lost but that so many survived.”


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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Nunavut COVID-19 Case Update
May 18/20

Confirmed cases=0

Probable cases=0

PUI cumulative total=948

PUI currently under investigation=261

*PUI (Persons Under Investigation) includes all individuals that meet the national PUI definition as well as some others self-monitoring or self-isolating.

*Please note: Every effort is made to keep this list up-to-date and complete but it may not reflect all individuals tested. Please keep that in mind when reviewing this information.

https://www.gov.nu.ca/health/informatio ... oronavirus
This may help to get an idea of what got distributed some Denisovan genes by huntergathers in paleolithic Asia and upto some other regions of the world:

https://www.nature.com/articles/d41586-020-01456-9

This suggests that farming in East Asia could have spread through mixing of farmers and hunter-gatherers, says Ling Qin, an archaeologist at Peking University in Beijing. That’s different from what ancient-genome studies have found in western Eurasia, where farmers with Middle Eastern ancestry largely replaced hunter-gatherers in Europe.
Most present day populations are highly interbred.
Most clear results may be seen only in isolated ethnic groups. And, whose genomes have changed luckily little, with time (not lost the most important parts of their Denisovan content).

Universe is a zero dimensional infinity.
 
Jun 6, 2020
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https://www.nature.com/articles/d41586-018-07374-1

Ancient genomics is recasting the story of the Americas’ first residents.
Trove of DNA from prehistoric inhabitants reveals that the continents’ early settlers moved far and fast.
Ewen Callaway.

The Montana baby, known as the Anzick boy, belonged to a population known as the Southern Native Americans, who are most closely related to present-day Indigenous populations from South America. They split from Northern Native Americans, who are genetically closer to many contemporary groups in eastern North America, around 14,600–17,500 years ago. The common ancestor of these two groups split from East Asians some 25,000 years ago, scientists established this year by sequencing the genome of 11,500-year-old human remains from Alaska.

Another lingering mystery surrounds a 2015 discovery, made independently by both Reich’s and Willerslev’s teams, that some modern inhabitants of the Amazon seem to share genetic ancestry with Australasian groups that include both the Papua New Guineans and Aboriginal Australians. Reich posited that this commonality points to a hitherto unknown migration to the Americas that vanished from all but the most isolated groups in the Amazon.

Willerslev, however, did link the genome of the 10,400-year-old individual from southeastern Brazil to an Australasian lineage.


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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"Although not present in the sequenced Denisovan genome, the distribution pattern and divergence of HLA-B*73 from other HLA alleles (involved in the immune system's natural killer cell receptors) has led to the suggestion that it introgressed from Denisovans into modern humans in West Asia."

I presume these modern humans were ancestral Austronesians who migrated along the sea coasts to south and southeast Asia, Australia, NewZealand, Oceania.
In south China they transferred the Denisovan genes to the farming communities which later, secondarily spread it to North china, Tibet, Mongolia, Taiwan, Japan and to the Americas.

Though dilution of this genetic engrossment would have taken place, still, the important point is, that it supports my hypothesis, that this engrossment helps to prevent total crippling of interferon production machinery by SARS-COV-2.
AS,
Only NK cells show activation response to macrophage derived cytokines in case of SARS-COV-2 infection. They serve to contain viral infections by secreting Interferon Gamma, while the adaptive immune response generates antigen-specific cytotoxic T cells that can clear the infection. NK cells work to control viral infections by secreting IFNγ and TNFα.

The next wave of modern humans from west Asia (the second wave of ancestral Austronesians injected into west Asia by the Sahara pump), which reached to settle in south-east Asia, did not contain the Denisovan engrossment in their genomes, because it had become extinct by then.

Note:
Neanderthal and Denisovan are cousins. Neanderthal was moved towards Europe and Denisovan moved towards Asia.
At some places they crossed. And at some places all three (third being modern man) Crossed. There was a fourth hominid too which crossed, about whom we only know from genetic engrossment, no fossils have been found.

Universe is a zero dimensional infinity.
 
Jun 13, 2020
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The only way to stop the common cold & presumably Covid 19 is to take massive doses of vitamin C, along with vitamin D3 & Zinc. The Zinc, according to reports, prevents the Virus from replicating. The vitamin C & D3 build your immune system.
My formula for heading off the common cold is 5000 mg at first sign of the cold & then 1000 mg per hour thereafter till symptoms subside. Then from there I taper off till it is obvious that the cold has gone. Interesting is that one time I had an appointment to have a root canal. Well, after all the vitamin C the tooth was no longer sensitive. It was 5 years before it bothered me again. This time it was just capped. So if you are going to have a root canal - try the vitamin C routine. My opinion - root canals are a dental rip-off.

You might try the vitamin C routine for the Covid 19 infection. I would take even more of the Vitamin C tho. They say to bowel tolerance - which you will notice as diarrhea. But take the Zinc & D3. Betting you can beat it. Vitamin C will cure anything - even cancer & heart disease. Research "Vitamin C Cures Cancer" .
 
Jun 6, 2020
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We need very isolated ethnic groups, since a long time, for this purpose.

I have selected some countries which are suitable for such a study. They also mark the movement of Denisovan genes.

China, Cambodia, Vietnam, Tibet, Mongolia, Madagascar, Laos, Papua New Guinea, Australian Northern Territory, Uzbekistan, Taiwan, Burundi, Botswana, Rawanda, Fiji, Namibia, Bhutan, Northeast India, Chattisgarh in India, Myanmar, Thailand, South Korea.

The death % from total confirmed cases of Covid-19 in these countries is very low and recovery rates very high.
Updated list
trying to track the movement of Denisovan genes.


Eastern region of Russian federation, New Zealand- Suburban and non- Urban (Maoris plus other Austronesian aboriginals), Myanmar (non- Rohangiya), Aboriginal Japanese, Aboriginal Thais, Aboriginal Chinese, Aboriginal Koreans,
Sri Lanka, Cambodia, Vietnam, Tibet, Mongolia, Belarus, Madagascar, Laos, Papua New Guinea, Australian Northern Territory, Uzbekistan, Rawanda, Uganda, Fiji, Namibia, Bhutan, Northeastern Indian states and Sikkim, Ladakh,Chattisgarh, Odisha, Bihar, Tamilnadu, Uttarakhand, Goa, Andman, Nicobar, Jharkhand-- all in India, Nepal, Saudi Arabia, Qatar, Singapore, UAE, Oman, Bahrain, Kazakhstan, Ghana, Guinea, Gabon, Djibouti, Kyrgyzstan, Iceland, Maldives, Venezuela, Equatorial Guinea, Guinea Bissau, Hong Kong, Ethiopia, Zambia, Costa Rica, South Sudan, Central African Republic, Palestine, Taiwan, Reunion Island, French Guiana, Eswatini, Faroe Islands, Gibraltar, French Polynesia, Macau, Bhutan, Eritrea, Saint Vincent and the Grenadines, Timor-Leste,
Grenada, New Caledonia, Saint Lucia, Dominica, Saint Kitts and Nevis, Falkland Islands, Greenland, Seychelles, Saint Barthelemy, Anguilla, Lesotho.

The death % from total confirmed cases of Covid-19 in these regions is low (0-1%) and recovery rates very high as compared to global trends.
Note: in few of the above places people with non Denisovan genetic engrossment are also having having high innate immunity due to some other ancient genetic engrossments.
The lifespan of animals which got infected with SARS-COV-2 is comparatively very less in the wild. Similarly the ancient hunter gatherer hominins reached puberty at a comparatively very less age than modern humans. The most aged, only a single skeleton, found till date of a modern man of 40,000 year ago, was found to be of just 40 years of age, which was severely arthritic. Most skeletons found are of teen age or younger.
Also in those times the population density was very less and so infectious disease burden was very less. So, probably adaptive immunity was of less survival value than innate immunity.
From the above information it seems logical to deduce that the Denisovan genetic engrossment, somehow bestows an enhanced innate immunity. And SARS-COV-2 seems more susceptible to innate immunity than adaptive immunity.

List is not comprehensive and final. Additions and deletions with time are expected to refine the gene transfer points by Ancestral Austronesian hunter gathers, and also their secondary transfer to other populations.

Universe is a zero dimensional infinity.
 
Jun 6, 2020
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Highlights of age and genetic reasons which caused COVID-19 fatalities in USA:

Out of the total 103,379 deceased

(1) 23,777 African Americans lost their lives. Mainly due to a genetic variant found exclusively in African Americans, that gets expressed during COVID-19 caused hypoxia. Hypoxia induced long QT syndrome (LQTS) and sudden cardiac death (SCD) contributing to the higher COVID-19-related mortality seen exclusively in "African Americans".

(2) Elderly population of USA was 52.512 million. They were more susceptible to COVID-19 caused death due to Comorbid conditions.
The population of NZ on the other hand is not even 5 million.

(3) Currently 1million people are over the age of 90 years in US.

(4) Since progestins in doses which prevent bleeding can increase the risk of thrombosis five to six fold, 32% of European American women who have inherited the progesterone receptor from Neanderthals (which in normal circumstances tends to prevent miscarriages and helps in giving birth to more children) were more likely to suffer from serious Covid-19 complications.

(5) Unlike China, Russian Federation, Vietnam, NZ, Lao People's Democratic Republic, Australian Northern Territory, Mongolia, Belarus, Taiwan, Tibet, Papua New Guinea, Madagascar, Srilanka, and many other regions listed by me previously, there was a dearth of people with Denisovan genetic engrossment in the population of USA.
Which if present around 30% in a population give the population a Pseudo Herd Immunity. I repeat, that this engrossment boosts the innate immunity, through NK cell secretions of Interferon Gamma and Tumor Necrosis Factor alpha, thus quarantining the cells long enough not only giving time for adaptive immunity to develop but TNF-ALPHA is directly SARS-COV-2 CIDAL.

It is therefore my prediction, that non of the vaccines currently
being developed will help enough, until some factors for boosting the NK cell secretions directly or through cytokine stimulus produced from tissue resident macrophages is/are co-linked with the vaccine. It is also possible, that just boosting the innate immune system alone can save lives as it is doing in the earliest Austronesian aboriginals.
 
Jun 6, 2020
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Why vaccines, drugs, monoclonal neutralizing antibodies being developed currently will not be satisfactorily effective against SARS-COV-2??

Short Answer:
The naked, "positive sense" single stranded genome of SARS-COV-2 has the capacity of intercellular transmission via vesicles containing its positive sense SS RNAs. These vesicles then facilitate virus spread to adjacent cells "lacking tight intercellular junctions," by collectively transferring multiple viral genomes into their cytoplasm. Cell lysis required to free the viruses and so come in contact with neutralizing antibodies may not always occur. The positive sense single stranded RNA does not require messanger RNA to translate itself. Only causing apoptosis of the cells containing it is a solution, which can destroy the intracellular viral RNA. This can only be achieved by using innate immune system cells.

Almost the whole human body, thus can virtually act as a single cell for SARS-COV-2.

In this scenario, not only the envelope surface protein neutralizing antibodies become useless, but also drugs targeting the viral RNA (like Remdesivir)would be required in doses which would be lethal for the patient.


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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In light of this previous post, data has started coming in. Judge it by yourself, how the efficacy is much less satisfactory than required.

(1) On Monday, Gilead Sciences announced the results from its Phase 3 SIMPLE trial, which found that hospitalised COVID-19 patients on remdesivir were 65 per cent more likely to see clinical improvement by the eleventh day compared with those who were not on the drug (This is being said by the developer of the drug, 65% and 11th day).

"Earlier treatment was suggested as a key factor in improved clinical outcomes."

Remdesivir will only be used in hospital or institutional settings and will have to be administered only with the “written informed consent” of each patient or their representative, said another source who is directly aware of the development.

"There is also a potential risk of the mortality rate increasing with extended use."

So, how to expect, that people will give "written informed consent" for the use of the drug earlier in the treatment which is being said as a key factor for improved clinical outcomes?

With data from: https://www.expresspharma.in/covid19-up ... -patients/

(2) First two vaccine results offer muted hope. Questions remain.

https://www.nature.com/articles/d41587-020-00015-x


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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the benefits of engrossment of the gene variant of Neanderthal in European females has recently been reported.
https://phys.org/news/2020-05-women-nea ... ldren.html

One in three women in Europe have inherited the progesterone receptor from Neandertals. 29 percent carry one copy of the Neandertal receptor and three percent have two copies.

The study shows that women who carry the Neandertal variant of the receptor tend to have fewer bleedings during early pregnancy, fewer miscarriages, and give birth to more children.
The above article may point to another important factor for greater death percentage of European females as compared to East Asian females when the following information is also considered:

Another very important component of the innate immune system, the Natural Killer cells ( have shown no significant difference in the uterus of women with recurrent miscarriage compared with controls. However, higher peripheral NK cell percentages occur in women with recurrent miscarriages than in control groups.

This prompts one to consider that a comparatively lower peripheral NK cells concentration occurs in 32% of European women who have a Neanderthal variant progesterone receptor engrossment as compared to East Asian females. If so, it implies a female organism with no Neanderthal variant progesterone engrossment is more dependent on innate immunity, and, therefore these women have a lesser probability to suffer from severe COVID-19 disease due to lesser coagulability of their blood.

I intend to support my thesis, that the primary obligatory weapon against SARS-COV-2 is our highly complex and ancient, innate immune system, and not the simple, modern adaptive immune system.

Any successful vaccine will have to address the involvement of the innate immune system in a large measure along with the usual adaptive immunity
developing immunogens, or pathogen neutralizing antibodies. The reason for this is, that SARS-COV-2 does not require cell lysis to move from one cell to the next (as described in a previous post), and, that it has a positive sense single stranded RNA and so does not require a messanger RNA to be translated in the host cell.


Universe is a zero dimensional infinity.
 
Jun 6, 2020
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https://www.medpagetoday.com/infectious ... id19/86261

Another case series from Iran too indicate : Seven pregnant women testing positive for COVID-19 died of cardiopulmonary complications.
Nine women in the series endured a range of cardiopulmonary complications including acute hypotension, persistent hypoxia, organ failure, acute respiratory distress syndrome, and cardiac arrest. Only one recovered; besides the seven who died, one remained critically ill and on ventilator support at the time of publication.
Women in this retrospective case series were not selected by any form of systematic surveillance, but were voluntarily reported cases of maternal morbidity and mortality in patients with severe COVID-19 disease.

WHILE........

Initial reports on more than 150 pregnant women from China indicated only one case of severe cardiopulmonary morbidity.



Though it is still early to come to any final conclusion, still, I think, we need to keep in mind that the above reported differences between the Chinese and Iranian females could be due to differences in their genetic engrossment with Neanderthal progesterone receptors.

An easy way to mark women who have genetic engrossment with the Neanderthal variant progesterone receptor is to look for visible hairs on their limbs ( when not artificially removed). Such women are common in Europe and from Middle East to North West India. While, from North East India to East Asia, Melanesia and in the ethnicities in the countries, a list of which I have posted previously (having comparatively very good innate capacity to recover from COVID-19) such women disappear ( naturally have smooth, hairless looking limbs).

Universe is a zero dimensional infinity.
 

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