Oak Ridge publishes "in-silico" COVID-19 study

These guys are onto something. This is the supercomputer that simulates nuclear chain reactions (ie - bombs). Good to see it put to a constructive use.

[elemental.medium.com]

Quick takeaways -

COVID = ACE inhibitor? Explains dry cough, loss of taste/smell.
Bradykinin storm, not cytokines? X-chromosome has double the receptors. Y-chromosome not so lucky.
Vitamin D! This one's getting confirmed everywhere now. Bells need to be rung.

Lots more in there.

Hi Wolfpack,

Here’s a link to the complete article, not some journalist’s hype on it.

A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm
[elifesciences.org]

Both ACE and ACE 2 are X-linked and you’re right this does explain some of the gender discrepancy for COVID-19. There’s a lot of good information in the article especially with respect to vitamin D, as you pointed out. It is true that SARS up regulates ACE2, but SARS2 not so much. This is because SARS-CoV2 suppresses alpha interferon versus SARS. Interferon may up regulate ACE2 but undertakes other antiviral actions. This is why COVID-19 is more infectious and releases more viral particles. On the other hand SARS triggers the release of more cytokines. This is why SARS is more lethal than SARS-CoV2.
But I also think there are a large number of contradictions.

Article Conclusions
1. A bradykinin storm not a cytokine storm is the mode of action for COVID-19
2. ACE2 is at the heart of the problem
3. ACE is good and helps counteract ACE2
4. ACE2 receptors are upregulated by COVID-19
5. The vitamin D receptor is down regulated by COVID-19
6. Enzymes that catabolize vitamin D are upregulated by COVID-19

There are many correct statements based on well known physiology and there are some highly speculative statements based on hypotheses that contradict not only well supported and established physiology but also the weight of clinical data.

Article Contradictions
1. ARBs and ACEIs should worsen clinical conditions, but they DECREASE morbidity and mortality
2. SARS2 does not unregulate ACE2 receptors because the virus suppressors interferon production (v SARS)
2. All the comorbid conditions are known to have increased ACE/ACE2 ratio and therefore should be relatively protected versus normals
3. With a higher ACE/ACE2 ratio the comorbids would be expected to have higher vitamin D levels versus normals
4. The predominance of COVID-19 patients have hypotension versus about 2/3 with hypertension in reality
5. Vitamin D inhibits the cytokine storm not the bradykinin storm



Hypotension can certainly arise from localized DIC and/or aggressive treatment of COVID-19 induced hypertension. Indeed the reference in the article to support their claim about the association between COVID-19 and hypotension does not even contain the word hypotension. The word hypertension occurs four times.

There are other perhaps more obvious contradictions.

Furthermore this is a study of nine bronchoalveolar lavage specimens from Wuhan, not exactly statistically significant and not exactly something on which one should base a mechanism that contradicts almost everything we know.

Why does this American study involve Wuhan specimens?
Why does it involve two separate medical schools and three other universities?
Why is the NIH and the US government funding research for this article?

You can make your own conclusions. I certainly have mine. But would love to hear others.



Edited 3 time(s). Last edit at 09/06/2020 07:40PM by PC, MD.