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COVID News You Can Use

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  • Sun, Feb 16, 2020 - 03:12pm

    #1
    pawch

    pawch

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    COVID News You Can Use

COVID NEWS YOU CAN USE

The following discussion supports three conclusions

1) COVID 19 might not be as devastating in the West as it seems to be in the East.
2) Angiotensin receptor blockers (ARBs like Losartan) may constitute an insurance policy against a fatal outcome (skip the below technical detail on this if you wish)
3) Beware the economic tsunami headed our way and don’t be distracted by the pandemic.

Conclusion #1

SARS (SARS-CoV1) and COVID 19 (SARS-CoV2) both enter cells in the lung via ACE2 receptors on their cell surfaces.
<https://www.nature.com/articles/s41586-020-2012-7&gt;

In a January 2020 study of uninfected lung cells from 8 normal donors (2 males, 1 Asian) the 2 male donors had a higher ACE2-expressing cell ratio than all 6 female donors (1.66% vs. 0.41% of all cells => 4x more). Furthermore, the only Asian donor (male) had a much higher ACE2-expressing cell ratio than the white and African American donors (2.50% vs. 0.47% of all cells => 4x more). <https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1.full&gt;

This was a small sampling but other articles demonstrate the same association between certain genes specific to Chinese and susceptibility to SARS.
<https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-6-106&gt;
<https://www.intechopen.com/books/hla-and-associated-important-diseases/association-between-hla-gene-polymorphism-and-the-genetic-susceptibility-of-sars-infection&gt;

The above suggests that in males and Han Chinese more ACE2 (the required “hero”) is necessary to counter balance ACE (the required “villain”) to maintain proper equilibrium in the RAS, putting them at greater risk for both SARS and COVID 19 (see Physiology discussion below on the RAS and why ACE2 is the hero and ACE the villain).

Nicotine upregulates ACE and down regulates ACE2
<https://www.ncbi.nlm.nih.gov/pubmed/30088946&gt;

68% of Chinese men smoke
<https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00340-2/fulltext&gt;

Aging in mice is associated with an upregulated ACE and down regulated ACE2
<https://www.hindawi.com/journals/omcl/2016/6731093/&gt;

Elite endurance athletes have decreased ACE activity (produce less angiotensin II)
<https://www.nature.com/articles/5200852&gt;

According to the emerging Chinese statistics, gender mortality is about 75:25 male/female with the vast majority of deaths in those over 60. The vast majority in this age group had a preexisting condition, such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), diabetes, …
<https://www.nytimes.com/2020/01/23/world/asia/coronavirus-victims-wuhan.html&gt;

Conclusion #2

PERTINENT ACE2 PHYSIOLOGY
The renin angiotensin system (RAS) primarily regulates blood pressure and operates through angiotensin converting enzyme (ACE). ACE converts circulating angiotensin I (inactive) to angiotensin II (active). This occurs at fixed ACE receptor sites inside capillaries in the lungs. Circulating angiotensin II then interacts with fixed angiotensin II type 1 receptors (AT1s) on endothelial cells (inside blood vessels) throughout the body.

This latter hormone 1) increases blood pressure and 2) triggers a cascade of powerful pro inflammatory cytokines (interleukins, tumor necrosis factors, growth factors, …).
Angiotensin II revisited: new roles in inflammation, immunology and aging
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377325/&gt;

Is angiotensin-II an endogenous pro-inflammatory molecule?
<https://www.researchgate.net/publication/7637021_Is_angiotensin-II_an_endogenous_pro-inflammatory_molecule&gt;

However, there is another component to the RAS, involving ACE2 and AT2s that counter regulate ACE and AT1s respectively. AT2s are especially prominent in the newborn. Is this why children seem to be less susceptible?

ACE and ACE2: a tale of two enzymes
<https://academic.oup.com/eurheartj/article/26/4/322/439241&gt;

ACE2 cleaves not only angiotensin I (already inactive) but also and especially angiotensin II, making it inactive. This down regulates both angiotensin II and its precursor angiotensin I.

There is soluble (circulating) ACE2 and membrane bound (fixed) ACE2.

SARS-CoV and COVID 19 (SARS-CoV2) bind to both of these receptor sites, entering lung cells through the fixed receptors. By binding to these receptor sites these viruses block the beneficial effects of both circulating and fixed ACE2. Treatment with soluble ACE2 (not available to the public) can overcome this.
<https://www.rndsystems.com/resources/articles/ace-2-sars-receptor-identified&gt;

Therefore, it appears that both SARS-CoV 1 and 2 (COVID 19) supercharge angiotensin II by blocking the counter regulatory activity of ACE2/AT2. This mechanism seems to be common to other viruses that target the lungs.

Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections  <https://www.ncbi.nlm.nih.gov/pubmed/24800825&gt;

Angiotensin II receptor blocker as a novel therapy in acute lung injury induced by avian influenza A H5N1 virus infection in mouse. <https://www.ncbi.nlm.nih.gov/pubmed/25655897&gt;

Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury.
<https://www.ncbi.nlm.nih.gov/pubmed/25391767&gt;

Angiotensin-converting enzyme 2 protects from severe acute lung failure injury.
<https://www.ncbi.nlm.nih.gov/pubmed/16001071&gt;

Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus failure.  <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728398/&gt;

February’s issue of Lancet is devoted to COVID 19 and one article describes it as creating  a “cytokine storm”. This hyper inflammatory response unrelated to the viral immune response is the usual cause of death.

Angiotensin II is a powerful pro inflammatory hormone integral to this cytokine storm.
<https://www.thelancet.com/coronavirus&gt;

By blocking ACE2 receptors, SARS and COVID 19 protect circulating angiotensin I and II, which would otherwise be removed. By blocking AT1s angiotensin receptor blockers (ARBs) limit the damage caused by angiotensin II mediated inflammation (cytokine storm). They are not involved in nor do they lower the immune reaction to the virus. But they do decrease the likelihood of a fatal outcome and provide time for the body to mobilize antiviral T and B cells.

The above discussion on ARBs has received precious little attention in mainstream medicine dominated by Big Pharma.

The World Health Organization (WHO), a highly politicized entity, has always favored vaccine research and has seemingly suppressed any therapy that deviates from a direct antiviral approach.

Vaccines have a checkered history with respect to efficacy, have an unavoidable time delay, have limited availability, and can have nasty adverse reactions, e.g., Gullain Barre, some worse than the disease, e.g., SARS vaccine, as Chris and Adam have mentioned.

Conclusion #3

The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated  <https://www.medrxiv.org/content/10.1101/2020.02.07.20021154v1.full.pdf&gt;

This virus cannot be contained and will sweep across the West, but fatalities will fall far short of predictions (Conclusion #1). The crisis loving media will distract the rank and file with the pandemic, while the negative economic consequences (from supply chain disruptions to deflationary defaults/bankruptcies) slowly expand despite ever increasing “not QE”. I have even written a book on this, portions of which were removed by Amazon without explanation. But that is a topic for another day.

PS I am a former lab director of a large medical center in Southern California, board certified in both Anatomic and Clinical Pathology with emphasis in microbiology. I have no affiliations with any institutions or organizations, political or otherwise, public or private. I’m retired but remain a lifelong student.

“When the student is ready, the teacher appears.”

  • Sun, Feb 16, 2020 - 03:20pm

    #2
    pawch

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    Reply To: COVID News You Can Use

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  • Mon, Feb 17, 2020 - 08:01am

    #3
    wyrldtraveler

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    Sample size

In a January 2020 study of uninfected lung cells from 8 normal donors (2 males, 1 Asian) the 2 male donors had a higher ACE2-expressing cell ratio than all 6 female donors (1.66% vs. 0.41% of all cells => 4x more). Furthermore, the only Asian donor (male) had a much higher ACE2-expressing cell ratio than the white and African American donors (2.50% vs. 0.47% of all cells => 4x more).

 

That’s an awfully small sample size to extrapolate such a conclusion.  What are the controls to eliminate the possibility that this is an outlier?

My concern is undue complacency by non-Asians and/or non-males.

  • Sun, Feb 23, 2020 - 08:09pm

    #4
    pawch

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    More on ARBs for SARS2

“[Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia]”
https://www.ncbi.nlm.nih.gov/pubmed/32061198 (Feb 16, 20220)

  • Wed, Feb 26, 2020 - 05:49pm

    #5
    Alexis

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    COVID News You Can Use

Thank you for writing up a detailed review if this! I’m interested to see if any of the numerous trials China is said to be running includes meds of this classification. I had a thought, if these are essentially anti hypertensive meds, how would you manage the possible adverse effects of too low bp from home, besides ensuring good hydration? I wondered in a hospital setting if they would counteract with Vasopresser if needed and if that would have any effect on the ace2 mechanisms. Gah, I hope they figure this out before it spreads like wildfire even more!

  • Wed, Feb 26, 2020 - 08:57pm

    #6
    pawch

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    COVID News You Can Use

Aloha Alexis,

Thank you for your post.

Although I am not a clinician, the typical hypertensive receives 50 to 100 mg of Losartan. My strategy is to use perhaps 25 mg, even though I am normotensive. When combined with excellent levels of vitamin D (>80 ng/ml) and good hydration as you mentioned, the strategy should be even more affective.

The ARB blocks the angiotensin II at the AT1 receptor. This thereby also blocks the negative feedback inhibition to renin. Vitamin D as you can see from the above diagram can independently replace this loss of renin inhibition resulting in lower levels of angiotensin I and angiotensin II. In addition Vitamin D especially but also vitamin C have tremendous benefits in retarding the development of ADES.

This approach using a ARBs is not preventative and would only be instituted after development of signs and symptoms of SARS 2 (shortness of breath, fever, decreased oxygen saturation). Getting a digital thermometer, pulse oximeter, and plenty of vitamin D3 geltabs containing 5000 IUs (in addition to the ARB of your choice) might be worthwhile. I have read that ARBs are slightly better at this then ACEIs.

 

  • Thu, Feb 27, 2020 - 01:32pm

    #7
    james donnell

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    COVID News You Can Use

Very interesting- I will follow this forum. Curious as to who decides it goes to “enter at your own risk ” status.

  • Sat, Feb 29, 2020 - 09:54am

    #8
    pawch

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    You can delay but not avoid, what to do?

Aloha James,

Thank you for keeping the topic alive.

To answer your question, it was my decision to post as a topic under “enter at your own risk.” It is controversial and I thought it might get lost in the shuffle otherwise.

To expand on the controversy, could Big Pharma thru highly politicized entities like WHO and the CDC, be constraining our therapeutic options? Why is it always highly expensive antivirals or dangerous vaccines? Why not recommend a cheap supplement (vitamin D) and a widely available, inexpensive medication (ARB)?

ACE2 and ARB animal studies (mice) have essentially already been done with influenza A H5N1, influenza A H7N9, respiratory syncytial virus (RSV), and acute lung injury (ALI)

https://www.ncbi.nlm.nih.gov/pubmed/24800825 https://www.ncbi.nlm.nih.gov/pubmed/25655897
https://www.ncbi.nlm.nih.gov/pubmed/25391767 https://www.ncbi.nlm.nih.gov/pubmed/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728398/

One note of explanation on the seeming contradiction that ACE2 is touted as beneficial, yet ACE2 receptors sites facilitate viral entry into cells.

There are two forms of ACE2 receptors, circulating and cell membrane bound. The circulating form soaks up much of the virus before it can attach to the fixed ACE2 receptors and gain entry. See diagram.

In the mouse studies recombinant ACE2 (r-ACE2) was injected. This ACE2 is produced in the lab, but is only commercially available for research, not the general public. Why is that?

I’ll venture an answer to that question with another.

“Besides creating an economic crisis, could SARS-CoV2 be solving existing ones, e.g., Medicare, Social Security, and pension crises (not to mention our trade imbalance)?”

Judging from those most at risk from SARS-COV2, the old and infirm with preservation of the young, maybe this should be considered.

This post may accelerate removal of access to PP. The deep state wants to keep you dumb and dependent, a VERY successful strategy to date.

In mid 2017 under a pseudonym I published (free online) a short book (20,000 words) connecting the dots (economic and historical) on the destination of our monetary system.

Eighteen months later I added an addendum more specifically predicting our immediate path forward. Without explanation Amazon expunged the addendum, although the book summary there still includes a reference to it. However it can still be read in its entirety at https://www.barnesandnoble.com/w/from-freedom-to-fascism-skip-sparks/1130048697

Just read “Plan B” in the addendum.

Good luck and God bless

  • Sun, Mar 01, 2020 - 01:43pm

    #9
    Bmarx

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    COVID News You Can Use

I came to the same conclusion RE: angiotensin II receptor blockers (ARBs) such as valsartan, losartan and irbesartan. All recalled?

https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan

 

  • Sun, Mar 01, 2020 - 02:54pm

    #10
    pawch

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    More on Losartan

Hi Bmarx,

I knew that valsartan had been recalled due to trace amounts of NDMA, a presumed carcinogen, but nothing about other ARBs. So thank you for the post and the link.

The drug hasn’t been recalled because of some unanticipated adverse reaction. Specific lots have been recalled, which have been discovered to contain NDMA above a certain threshold.

I have friends that presently take losartan. I presume, perhaps unwisely, that ARBs presently available are not from those lots.

I guess it all boils down to the risk benefit ratio. This is somewhat dependent on age. Carcinogens don’t lead to cancer all the time and certainly not overnight. Cancers are generally not considered of carcinogenic origin, unless duration of exposure to the carcinogen has been longer than 5 to 10 years.

I’m personally only taking it for a few weeks at most. Furthermore, I have less time to develop an implicated cancer.
But we all make our own decisions. Unfortunately most are based on emotion (myself included).

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