
Supercomputer analysis of Covid-19 leads to new theory - mvgoogler
https://elemental.medium.com/a-supercomputer-analyzed-covid-19-and-an-interesting-new-theory-has-emerged-31cb8eba9d63
======
woeirua
Seems like it should be really straightforward to determine if this hypothesis
is right by measuring bradykinin levels in Covid patients versus non-Covid
patients.

One thing that I think strongly suggests that this hypothesis is wrong is that
there is no strong relation between ACE-inhibitors and Covid mortality.
Indeed, most of the studies that I've seen suggest that ACE-inhibitors have a
somewhat protective effect whereas ARBs actually seem to have a minor
detrimental effect [1]. So for the article to claim that covid behaves
pharmacologically like ACE-inhibitors seems wrong at face value.

[1]
[https://www.nejm.org/doi/full/10.1056/NEJMoa2007621](https://www.nejm.org/doi/full/10.1056/NEJMoa2007621)

~~~
michaelhoffman
The cited article has been retracted.

(I know this because I have the PubPeer extension installed which puts a big
red warning by it.)

~~~
Crye
It shows for me too and I don't have the PubPeer add on

~~~
toxicFork
The addon makes it show on the HN comments page

------
hellofunk
> Interestingly, Jacobson’s team also suggests vitamin D as a potentially
> useful Covid-19 drug. The vitamin is involved in the RAS system and could
> prove helpful by reducing levels of another compound, known as REN. Again,
> this could stop potentially deadly bradykinin storms from forming. The
> researchers note that vitamin D has already been shown to help those with
> Covid-19. The vitamin is readily available over the counter, and around 20%
> of the population is deficient. If indeed the vitamin proves effective at
> reducing the severity of bradykinin storms, it could be an easy, relatively
> safe way to reduce the severity of the virus.

~~~
shubhamjain
This Medium article was written on March 10 [1].

"Put simply, medics found that severely ill flu patients nursed outdoors
recovered better than those treated indoors. A combination of fresh air and
sunlight seems to have prevented deaths among patients; and infections among
medical staff.[1] There is scientific support for this. Research shows that
outdoor air is a natural disinfectant. Fresh air can kill the flu virus and
other harmful germs. Equally, sunlight is germicidal and there is now evidence
it can kill the flu virus."

[1]: [https://medium.com/@ra.hobday/coronavirus-and-the-sun-a-
less...](https://medium.com/@ra.hobday/coronavirus-and-the-sun-a-lesson-from-
the-1918-influenza-pandemic-509151dc8065)

~~~
kovek
That air is a natural disinfectant is super interesting.

I read that vitamin D and observed benefits for those who have vitamin D is a
correlation. Meaning that taking vitamin D supplements might not be as helpful
as getting sunlight (a natural way to get vitamin D)

~~~
mcguire
I don't know about air, but ultraviolet light is a pretty good disinfectant.

~~~
trhway
ozone too. And it goes inside your nose, throat, lungs.

~~~
robbyt
I'm still waiting for the results from that whole bleach in the lungs idea
Trump had. Hoping that will be the cure for all of this.

------
zby
They found out that some genes related to ACE in comparison to genes related
to ACE2 are more 'expressed' in Covid patients than normally and they conclude
that that must have resulted in too much bradykinine. Hmm - that strikes me as
kind of roundabout - why they couldn't just measure bradykinine levels
directly? Is that too hard?

"Here, we perform a new analysis on gene expression data from cells in
bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to
sequence the virus. Comparison with BALF from controls identifies a critical
imbalance in RAS represented by decreased expression of ACE in combination
with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and
many kallikrein enzymes that activate it, and both bradykinin receptors. This
very atypical pattern of the RAS is predicted to elevate bradykinin levels in
multiple tissues and systems that will likely cause increases in vascular
dilation, vascular permeability and hypotension."

~~~
08-15
> why they couldn't just measure bradykinine levels directly? Is that too
> hard?

It is. To measure gene expression, you isolate total mRNA and sequence it.
This tells you the expression of all genes simultaneously. The protocol is
fairly standard, cheap, and quick. That doesn't tell you anything about
bradykinine, though, because there is no mRNA that codes for it.

In contrast, no such protocol exists for proteins. Sequencing a single protein
is comparatively difficult, and no high throughput device exists that
sequences lots of proteins, let alone quantifies their abundance. The
traditional lab methods like PAGE gels are slow and labor intensive.

~~~
robwwilliams
This comment on quantitative protein assays is only partly correct. It is
definitely harder than quantitative assays of messenger RNA (aka “gene
expression” and not as comprehensive. But there are now hundreds of
quantitative proteomic studies that survey 5000 or more proteins in single
samples (and their peptide fragments). Search PubMed for the author “Aebersold
R”.

~~~
AnthonBerg
Thank you for a great comment!, the crisp context is a good gateway for
further reading.

Could I ask you for any hints about where/how to learn more? And/or if there's
a way to follow your work online?

------
ChrisArchitect
it's annoying that this is not a 'new' article/theory. It is an article
talking about some research and analysis from TWO MONTHS ago. Almost want to
request a (July 2020) marking in the title as we do with old link posts

~~~
sydd
Actually the theory is even older, here's an article from the beginning of
April: [https://www.radboudumc.nl/en/nieuws/2020/radboudumc-
research...](https://www.radboudumc.nl/en/nieuws/2020/radboudumc-researchers-
publish-new-insights-into-covid-19)

If this info has been out since 5 months I'd expect several trials already
that target the bradykinin storm.

------
debacle
The study itself:

[https://elifesciences.org/articles/59177](https://elifesciences.org/articles/59177)

Excerpts from the abstract:

    
    
        Bradykinin is a potent part of the vasopressor system that induces
        hypotension and vasodilation and is degraded by ACE and enhanced by 
        the angiotensin1-9 produced by ACE2.
    

...

    
    
        This very atypical pattern of the RAS is predicted to elevate 
        bradykinin levels in multiple tissues and systems that will likely 
        cause increases in vascular dilation, vascular permeability and 
        hypotension.
    

[https://en.wikipedia.org/wiki/Bradykinin](https://en.wikipedia.org/wiki/Bradykinin)

------
Aromasin
This is a really interesting theory, and explains to some degree why those
with darker complexions (lower vitamin-D levels) and obesity (increased rates
of hypertension) have higher mortality rates. Would it explain why younger
people are much less effected though?

------
robomartin
Am I the only one bothered by the use of “theory” when this is a hypothesis
and, in particular, the back and forth flipping between the two terms in the
article?

~~~
TheSpiceIsLife
Probably just you ;)

Lay people use the two interchangeably.

In at least two of the thesaurus I have at hand _hypothesis_ is synonymous is
_theory_.

~~~
andrewflnr
It seems to me like even scientists use the terms not quite interchangeably,
but on a spectrum. String theory is still "theoretical physics", not
"hypothetical physics", even though it will likely never be tested in our
lifetime.

~~~
zuminator
That's because the whole internet idea of "a theory is a well-tested
hypothesis" is silly and wrong. A hypothesis is a specific supposition or
question about the way things work which if true has some level of explanatory
power in a field of study. It can be confirmed or unconfirmed. It's still a
hypothesis. An answered question is still a question.

A theory is a explanatory framework for a body of knowledge. Unlike a
hypothesis, it's not inherently a question or a guess. That doesn't mean it's
"true." It also can be unconfirmed (as you say, string theory) or even
demonstrably false (phlogiston theory, Ptolemaic theory) and still be a
theory.

Obviously there's considerable overlap between the two concepts and as you say
they are sometimes used almost interchangeably. Colloquially, "I'm testing my
hypothesis that orally ingesting booze provides protection against infection,
which if confirmed will be a key part of a theory of booze immunology" gets
collapsed into "I'm testing my theory of booze immunology." Big deal. It
really only matters because people let themselves get bent out of shape about
the whole "evolution is just a theory" thing.

And since I'm ranting already, evolution isn't "just a theory" because
evolution itself isn't a "theory," evolution is the natural phenomenon that is
being theorized about.

~~~
andrewflnr
Right. I'll only add that it's not really an "internet idea". It's a highly
idealized, cartoon version of science that has been part of my education since
long before I was on the internet.

------
w1zard0f0z
Is this a fake news?

I could find only the article below on IBM's news section (they created this
super computer). Speaking about the results of the 2 day analysis, Jeremy
Smith, Governor’s Chair at the University of Tennessee, director of the
UT/ORNL Center for Molecular Biophysics, and principal researcher in the
study: “Our results don’t mean that we have found a cure or treatment for
COVID-19. We are very hopeful, though, that our computational findings will
both inform future studies and provide a framework that experimentalists will
use to further investigate these compounds. Only then will we know whether any
of them exhibit the characteristics needed to mitigate this virus.”

[https://newsroom.ibm.com/US-Dept-of-Energy-Brings-the-
Worlds...](https://newsroom.ibm.com/US-Dept-of-Energy-Brings-the-Worlds-Most-
Powerful-Supercomputer-the-IBM-POWER9-based-Summit-Into-the-Fight-Against-
COVID-19)

------
gchokov
Vitamin D for the win!

~~~
hosh
We don’t know the dosage or protocol for stopping the bradykinin storm, or
even if this hypothesis is confirmed through more tests ... but it seems
sensible to me to make sure one has a healthy level of Vitamin D, and that is
actionable for a lot of people.

~~~
throwaway43234
> that is actionable for a lot of people

Really hoping this is better by the next few months or my Seattle winter will
be even more pill popping to maintain basic human functionality....

~~~
hosh
If you cook or grow your own food (microgreens, mushroom in a kitchen
cabinet), there are alternatives.

For example: [https://www.milkwood.net/2014/03/31/want-extra-vitamin-d-
pla...](https://www.milkwood.net/2014/03/31/want-extra-vitamin-d-place-your-
shiitake-mushrooms-in-sunlight/)

This works for both shiitake and button (portobello) mushrooms.

This trick came from Paul Stamets, one of the world’s foremost mycologist. He
is based out in Casscadia. You may have to track down exactly what “2 days”
means... I wouldn’t be surprised if he went looking for a way to maintain his
Vitamin D health.

You only need 10g of this four times a week, according to this article. While
it is summer time in Seattle, you can prepare a bunch and then dry them, so
they last until next spring.

~~~
gchokov
This is a great insight, thank you.

------
dekhn
I can't really see why you would need a supercomputer to do the analysis they
did (it shows SC centers are getting desperate for users; I wouldn't even have
been allowed to run this code on a supercomputer when I was an academic,
because it didn't need interconnect for strong scaling.

~~~
searine
>I can't really see why you would need a supercomputer to do the analysis they
did

The article is fluff.

98% of all bioinformatics is done on "supercomputers" or 'high performance
computing environments" saying the researchers used supercomputers to analyze
the expression data is like saying someone used a shovel to dig a hole.

~~~
tzs
The article doesn't simply say they used a supercomputer. It says they used
Oak Ridge's Summit supercomputer, the second fastest in the world. Unless 98%
of all bioinformatics done on a top 2 supercomputer, your point fails.

~~~
searine
>It says they used Oak Ridge's Summit supercomputer, the second fastest in the
world.

The shovel had racing stripes. Got it.

The job doesn't change based on what hardware it is run on.

------
mensetmanusman
The hard part is asking the question in a way a computer can provide a
meaningful answer.

~~~
hughw
In spite of its title, the article gives us no clue how the investigators used
the supercomputer.

~~~
vermilingua
The intro made it sound like they just ran an exhaustive search of all nCoV
genes against a database of known genes and their effects.

------
mleonhard
The journal provides a good summary of the paper:

[https://elifesciences.org/articles/59177](https://elifesciences.org/articles/59177)

------
navd
Does this support nicotine as a therapeutic for covid?

It supposedly acts on the RAS and down regulates ace2

~~~
augusto-moura
Maybe, I found out a study[1] that suggest that nicotine helps in the vascular
metabolism of bradykinin. I'm no researcher neither understand a lot o
biology, but it could be a hint

[1]:
[https://journals.physiology.org/doi/full/10.1152/ajpregu.000...](https://journals.physiology.org/doi/full/10.1152/ajpregu.00099.2018)

------
jakobmartz3
Whether or not this hypothesis is truly correct, it still seems valid and I
would much rather take Vitamin D then Chloroquine...

~~~
notatoad
Vitamin D is lipid-soluble - your body will not flush any excess, and build-up
can have negative health consequences. Probably don't start taking vitamin D
supplements without getting your current vitamin D levels tested first.

------
secondcoming
Interesting, it seems to explain most aspects of the virus infection, _except_
for the scenario where a carrier exhibits little or no symptoms

~~~
jfoster
Could that be determined by something like the level of Vitamin D a person
has?

------
klysm
The anthropomorphization of computers (especially powerful ones) is pretty
annoying. A _person used a supercomputer_ to analyze Covid-19, and I’m
guessing the theory didn’t just ‘emerge’ from the computer.

~~~
falcor84
I remember a professor of mine (I forgot in which class) saying that humans
generally make up 3 kinds of explanations about a system's behavior:

1\. When a system is very simple, we explain its actions in terms of its
properties and external forces acting on it.

2\. When it's a medium complexity system, we tend to explain its actions in
terms of its design, putting ourselves in the designer's shoes.

3\. When it's a complex enough goal-seeking system, we begin to empathise with
the system itself, thinking why "it chose" a course of action.

I remember how impressed I was with this classification and how much sense it
made in terms of how we're able to understand the world and predict what will
happen next.

From this angle, much of modern computer software is clearly in category 3,
and it just makes things easier for us to think of it as having a mind of its
own.

~~~
pacaro
For category three I feel that goal-seeking (or the appearance of such) is
sufficient for the anthropomorphism to kick in. The braitenberg vehicles
thought experiment is a good example of this.

Quoting from wikipedia "For the simplest vehicles, the motion of the vehicle
is directly controlled by some sensors (for example photo cells). Yet the
resulting behaviour may appear complex or even intelligent."

[https://en.m.wikipedia.org/wiki/Braitenberg_vehicle](https://en.m.wikipedia.org/wiki/Braitenberg_vehicle)

~~~
ISL
I routinely anthropomorphize PID loops when tuning them.

One of the best nuclear astrophysicists I know thinks about stars as entities
that want to stay alive -- "I'm running out of hydrogen, what can I burn
next?" That approach yields the right phenomenology almost all the time.

~~~
Tarq0n
That makes sense for really old things like stars, after all survivorship bias
is a critical factor in most long lasting things we observe.

------
antipaul
“Jane Zu read something online and says it’s interesting”

------
arkanslaw
Boy oh boy that computer sure is super! (har har!)

