[HN Gopher] SARS-CoV-2 Spike Protein Impairs Endothelial Functio...
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       SARS-CoV-2 Spike Protein Impairs Endothelial Function via
       Downregulation of ACE2
        
       Author : fortran77
       Score  : 145 points
       Date   : 2021-05-02 14:30 UTC (8 hours ago)
        
 (HTM) web link (www.ahajournals.org)
 (TXT) w3m dump (www.ahajournals.org)
        
       | russfink wrote:
       | Would someone please dumb this down for me?
        
       | podgaj wrote:
       | So if ACE2 is downregulated, and ACE2 uses zinc as a cofactor,
       | why are they not looking at high doses of zinc as a treatment?
       | 
       | https://www.uniprot.org/uniprot/Q9BYF1
        
         | nradov wrote:
         | Zinc supplements are part of the recommended prevention and
         | treatment protocol. There is some research to indicate that
         | Quercetin facilities zinc uptake.
         | 
         | https://covid19criticalcare.com/covid-19-protocols/i-mask-pl...
        
         | jm4 wrote:
         | When I was hospitalized for covid, they were giving me zinc
         | (among other things) every day.
        
           | podgaj wrote:
           | Yes, I've already known about that. I'm just wondering why
           | they're not checking peoples zinc levels or why they're not
           | recommending people supplement with zinc.
           | 
           | The rate of zinc deficiency in India is near 50%!
           | 
           | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702335/
        
       | fortran77 wrote:
       | Link to full PDF:
       | https://www.biorxiv.org/content/biorxiv/early/2020/12/04/202...
        
       | stevemk14ebr wrote:
       | Can someone ELI5 please? My field is low level computer systems,
       | and unfortunately that knowledge does not extend to low level
       | physiological processes!
        
         | 908087 wrote:
         | Don't let that stop you from pretending to be an expert in
         | other fields. It doesn't stop anyone else here.
        
       | unanswered wrote:
       | If this is a function of the spike protein, doesn't that mean the
       | mRNA vaccines cause this effect as well?
        
         | TheAdamAndChe wrote:
         | The spike protein from the virus bands to ACE2 receptor,
         | messing them up. The vaccine primes our bodies to attack the
         | spike protein, preventing it from binding to ACE2 and thus
         | preventing it from messing up ACE2 receptors.
        
           | ronri19 wrote:
           | But the vaccine causes the body to produce spike protein. The
           | CDC emphasizes the spike protein is harmless, but this new
           | research finds that the spike protein itself can cause
           | damage. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/di
           | fferent...
        
             | fnordpiglet wrote:
             | The vaccine instructs cells to produce a piece of protein
             | from the spike. There's no such thing as "a" spike protein,
             | the spike is a structure of proteins that enable a lot of
             | functions for the virus. They choose a piece of protein
             | from the structure that's antigenic then encode the mRNA to
             | produce that. The mRNA is delivered into the cell by the
             | lipid transport and the cell picks up the instruction and
             | produces the antigenic protein fragment. Your immune system
             | responds as expected and attacks the antigen carrying
             | things - existing cells included. The inoculated mRNA is
             | quickly broken down because mRNA is a standard process in
             | cell function.
             | 
             | Unless the effect observed is due to the antigen the
             | vaccine produces then you wouldn't expect to see the same
             | behavior in vaccinated humans as they saw experimentally
             | with a full virus, even if some part or the full assembly
             | of the spike is a cause for cellular damage.
        
               | wpasc wrote:
               | From the wikipedia for Pfizer, the vaccine supposedly
               | produces a full length spike protein [1]
               | 
               | https://en.wikipedia.org/wiki/Pfizer%E2%80%93BioNTech_COV
               | ID-...
        
               | yborg wrote:
               | No.
               | 
               | From that link "...two proline substitutions (K986P and
               | V987P, designated "2P") that cause the spike to adopt a
               | prefusion-stabilized conformation reducing the membrane
               | fusion ability, increasing expression and stimulating
               | neutralizing antibodies..."
               | 
               | It's a modified version of the spike protein designed as
               | an antibody target, not to identically replicate the
               | spike protein function.
        
             | karmicthreat wrote:
             | Your body is non-stop taking damage every day. Its when the
             | body can't compensate fast enough that its a problem.
             | 
             | The load from an mRNA vaccine is miniscule compared to
             | severe, or moderate covid.
        
             | lamontcg wrote:
             | The vaccine causes a relatively tiny amount of spike to be
             | produced compared with a raging infection.
             | 
             | A little bit of spike trains your body to identify it and
             | neutralize it.
             | 
             | A whole lot of spike is toxic to your organs and damages
             | them.
             | 
             | To downregulate ACE2 you need a whole lot of receptor
             | activation and a lot of ligands floating around in your
             | system binding to it to cause that. The dose of spike
             | protein matters.
        
               | podgaj wrote:
               | To downregulate ACE2 all you need is a bad enough zinc
               | deficiency.
        
             | gameswithgo wrote:
             | This has been the clever guy hot take for a few days now.
             | Yet millions of people are walking around vaccinated
             | without damage, so....
        
               | platz wrote:
               | It's a question hacker mindset would ask. What follows
               | from first principles given the headline; it's not an
               | unreasonable question, even if there is no empirical
               | evidence the vaccines are unsafe
        
               | ronri19 wrote:
               | We also have 150+ million people around the world who've
               | had the virus walking around without damage.
               | 
               | The point is how should we change our recommendations?
               | Are older people or others with certain medical
               | conditions more susceptible to damage?
               | 
               | I don't see how shrugging off this new information is
               | reasonable or scientific.
        
               | podgaj wrote:
               | Start by telling people to take more zinc.
        
               | podgaj wrote:
               | People downvoting nutrition...I don't get it...or maybe I
               | do.
               | 
               | https://www.sciencedirect.com/science/article/pii/S240545
               | 772...
               | 
               | Vitamin D levels had a significant difference between the
               | case and control groups (p = 0.008). Serum calcium and
               | serum zinc levels also had statistically significant
               | differences between the two groups (p < 0.001).
        
               | tediousdemise wrote:
               | Or walking around damaged, and they don't know it yet.
               | 
               | Didn't it take us thousands of years to realize lead was
               | poisonous?
        
               | shadowgovt wrote:
               | It didn't. Western medicine new lead was poisonous dating
               | back at least to the second century BCE. What changed was
               | the belief that only acute lead exposure could cause
               | poisoning... We came to understand the mechanisms by
               | which chronic exposure causes buildup and poisoning over
               | a long term.
        
               | briefcomment wrote:
               | This makes the analogy even more appropriate. We know the
               | spike protein is harmful in some amount, but we think a
               | small enough amount produced forever should be safe.
               | Maybe we'll learn otherwise.
        
               | rrss wrote:
               | > small enough amount produced forever should be safe
               | 
               | does 'forever' modify 'produced' or 'should be safe'? if
               | the former, what produces a small amount of the spike
               | protein forever (continuing, not just a small amount one
               | time)?
        
               | yborg wrote:
               | Why do you think it is produced forever? The mRNA quickly
               | degrades in the body and the injected cells will stop
               | producing the spike protein. That's why there has to be a
               | second injection.
        
               | rzz3 wrote:
               | Is there a source? 100% believe you, but due to the
               | conflicting posts I'd love to read the source (and I
               | don't know what to Google). Thanks!
        
               | Kubuxu wrote:
               | (m)RNA is inherently unstable in our body:
               | https://en.wikipedia.org/wiki/Messenger_RNA#Degradation
        
             | Alex3917 wrote:
             | > this new research finds that the spike protein itself can
             | cause damage.
             | 
             | Downregulation of ACE-2 causes damage, not the spike
             | protein. The spike protein itself causes downregulation,
             | but not enough to cause damage.
        
             | retrac wrote:
             | It causes the body to produce it in a limited, fixed
             | quantity in proportion to the number of viable RNA strands
             | that make it into a cell, largely localized at the
             | injection site. Just a guess but this probably means its
             | risk is extremely limited.
             | 
             | The wild virus causes this protein to be produced without
             | check.
             | 
             | It wouldn't just be the mRNA vaccines, anyway. The viral
             | vector ones, as well as the inactivated virus, and the
             | spike protein unit extract ones, all involve getting some
             | of the spike protein either made in the cells, or introduce
             | it directly.
        
               | beagle3 wrote:
               | Indeed. But it's a nontrivial question of numbers.
               | 
               | The vaccine has to be orders of magnitude safer than the
               | virus, because (essentially) everyone will get the
               | vaccine, but only some will get the disease. E.g. it
               | might be harmful to vaccinate people in New Zealand and
               | Australia at this point, because for now they cannot get
               | the virus.
               | 
               | What these papers (there are 3 independent ones showing
               | very similar results, all coming out in the last month)
               | show is that the vaccine outcome (specific proteins) that
               | were assumed to be inert and _only_ prime the immune
               | system against the virus, are actually active and
               | damaging. That 's a big difference -- and the question of
               | whether it makes sense to vaccinate needs to rely on
               | actual science, not "it's a vaccine so must be good and
               | safe" ideology. It also depends on specific attributes
               | (e.g. age, obesity, etc.)
               | 
               | There's an Israeli study showing myocarditis at a rate of
               | 1:20,000 for the 16-30 age bracket, with 1:100,000
               | overall (all pfizer)[0] ; the US Army stats are 1:250,000
               | (for a mix of JNJ,Pfizer.Moderna) but I didn't find age
               | distribution - and these are exceptionally lean and fit
               | individuals, compared to the general population.[1]
               | 
               | That's just myocarditis ; it it related to what's
               | described in this paper? I don't know. Are there any
               | other issues? I don't know. And generally speaking, no
               | one else does either. But because _everyone_ gets
               | vaccinated, we require exceptional proofs of safety. Or
               | at least, did before 2020.
               | 
               | [0] https://www.timesofisrael.com/israel-said-probing-
               | link-betwe...
               | 
               | [1] https://www.military.com/daily-
               | news/2021/04/26/pentagon-trac...
        
               | maxerickson wrote:
               | We are getting close to 2% of the planet having a
               | confirmed case.
               | 
               | New influenza vaccines (using cell lines) were approved
               | after use in 15,000 people, ~10 years ago:
               | https://www.fiercepharma.com/vaccines/novartis-receives-
               | fda-...
               | 
               | Are you overestimating the safety testing done on other
               | vaccines?
               | 
               | Of course these are the first widely used vaccines for
               | corona viruses and use new technologies to boot, so
               | there's a lot more to it, but I wonder how you've gone
               | about assessing previous safety proofs.
        
               | krona wrote:
               | Cell culture technology has been in use for decades
               | around the world for many other vaccines, going back 35
               | years at least (e.g. rabies/polio).
               | 
               | Genetic/DNA vaccines are new.
        
               | beagle3 wrote:
               | > New influenza vaccines (using cell lines) were approved
               | after use in 15,000 people
               | 
               | The are several important differences: (1) it took 4
               | years of data, not 6 months of data like Pfizer, (2)
               | using mature, well known technology.
               | 
               | Now, let's compare to a flu vaccine approved with an EUA
               | after 6 months, shall we?
               | 
               | https://www.bmj.com/content/362/bmj.k3948
               | 
               | https://www.sciencemag.org/news/2015/07/why-pandemic-flu-
               | sho...
               | 
               | (Both articles describe the same vaccine, pandemrix)
               | 
               | It caused narcolepsy, a few hundred cases of it. That's a
               | debilitating, life changing disease; by all estimates I
               | know, much worse than the flu it was supposed to prevent.
               | It's not the only case (though there aren't maney - 1976
               | flu vaccine causing guillan-barre, dengvax worsening
               | dengue, israeli anthrax vaccine causing harm, probably a
               | couple more I'm unaware of; the vast majority of vaccines
               | -- all that I'm aware of that got full approval rather
               | than an EUA - have a 1:1,000,000 or better adverse event
               | profile).
               | 
               | And it isn't even perfectly clear _why_. The science
               | article says it 's likely because there's a similarity
               | between some viral protein and some brain protein -- but
               | that's not clear that's the reason. According to the BMJ
               | article, basically the same vaccine but with a different
               | adjuvant caused none of the issues.
               | 
               | How long did it take to figure this out? Approximately
               | one year of data.
               | 
               | I urge you to read the BMJ article - it eerily describes
               | exactly what's happening now, 11 years ago - some of the
               | names (e.g. Fauci) haven't changed; some have.
               | 
               | > Are you overestimating the safety testing done on other
               | vaccines?
               | 
               | I don't think I am. That's why we have VAERS and a
               | European equivalent. You might notice that a lot of the
               | touted efficiency and safety data is coming from Israel.
               | Well, Israel has no VAERS equivalent, hardly tracks any
               | adverse events for this vaccine (likely on purpose), and
               | decreed that vaccinated people are not to be PCR tested
               | unless they show obvious COVID symptoms, whereas
               | unvaccinated are required to have negative test from the
               | last 48 hours for many activities -- which means the data
               | will show it's working even if it doesn't. Israeli data
               | is rubbish, other data is hardly available. (I currently
               | live in Israel and track this; It's been politicised in
               | Israel to the point that no data coming out of Israel is
               | trustworthy)
               | 
               | So, regardless of safety of other vaccines, we have very
               | little reliable data about the new guys.
               | 
               | > but I wonder how you've gone about assessing previous
               | safety proofs.
               | 
               | By waiting enough time to get data accumulated.
               | 
               | You know why we ddin't have any corona virus vaccine
               | before 2020? It's not for lack of trying. They all failed
               | at various stages, all of which were skipped for the
               | SARS-Cov-2 vaccines.
        
               | maxerickson wrote:
               | _You know why we ddin 't have any corona virus vaccine
               | before 2020? It's not for lack of trying. They all failed
               | at various stages, all of which were skipped for the
               | SARS-Cov-2 vaccines._
               | 
               | You can't run a trial if there aren't any people getting
               | infected.
               | 
               |  _By waiting enough time to get data accumulated._
               | 
               | This isn't a mechanistic explanation of how you've
               | arrived at a stronger level of comfort with earlier
               | safety trials, unless your evaluation criteria is
               | literally just that they took longer.
        
               | beagle3 wrote:
               | > You can't run a trial if there aren't any people
               | getting infected.
               | 
               | Corona viruses have been with us for a few thousand
               | (millions?) of years. It is estimated 25% or so of colds
               | are caused by corona viruses. And not surprisingly, they
               | can also cause really, really bad outcomes in the sick
               | and elderly -- in fact, there is some speculation that
               | before they became endemic, they were as virulent as
               | sars-cov-2.
               | 
               | And there definitely have been attempts; not as focused,
               | of course, but nevertheless over many years. The most
               | focused attempts were at SARS-Cov-1 and MERS - and both
               | burned out quickly - but also all failed spectacularly at
               | the animal testing stage.
               | 
               | > This isn't a mechanistic explanation of how you've
               | arrived at a stronger level of comfort with earlier
               | safety trials, unless your evaluation criteria is
               | literally just that they took longer.
               | 
               | (a) animal testing (skipped entirely in this case, which
               | would have shown perhaps that targeting the spike protein
               | may be an issue, and
               | 
               | (b) yes, more time. some signals take time to surface -
               | do read the pandermix papers I linked to. Whatever is
               | happening now is just too close for comfort, and I
               | sincerely hope it will end better.
               | 
               | What more can you ask for, when I show you a horrible
               | experiment from 2009, which matches in almost every
               | possible way except we're now using now technology? With
               | articles from science and the BMJ? Is there anything that
               | can satisfy your request for reasonable doubt?
        
               | maxerickson wrote:
               | There were animal studies:
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449230/
               | 
               | I was just asking to understand your reasoning, I wasn't
               | asking you to convince me it was correct, and I'm not
               | trying to convince you it isn't correct.
        
               | beagle3 wrote:
               | Thank you, I failed to find this one in my previous
               | literature search.
               | 
               | I don't have it handy now, but for at least one SARS-
               | Cov-1 vaccine candidate everything seemed fine, and good
               | immediate antibody response (as in this paper), but
               | another challenge 3 months later had an ADE response with
               | worse outcomes than a naive infection. IIRC it was done
               | in felines, not in primates.
        
               | Izkata wrote:
               | > Basel, November 20, 2012 - Novartis announced today
               | that the US Food and Drug Administration (FDA) approved
               | the use of Flucelvax(r) (Influenza Virus Vaccine), the
               | first cell-culture-derived vaccine, for individuals 18
               | years of age and older3.
               | 
               | > A multinational, randomized, observer-blinded, placebo-
               | controlled trial was performed to assess clinical
               | efficacy and safety of Flucelvax during the 2007- 2008
               | influenza season in adults aged 18 to 49 years in the US,
               | Finland and Poland3.
               | 
               | They took ~4 years to approve it, sounds like they were
               | more cautious for Flucelvax.
        
               | Godel_unicode wrote:
               | Myocarditis is significantly under-diagnosed in young
               | adults, but is believed to be on the order of 10 cases
               | per 100,00 per year in the population.
        
               | beagle3 wrote:
               | Perhaps, I couldn't find reliable data, and apparently
               | neither do the people doing the Israeli study (that much
               | is stated in the copy of it that was leaked ; it's in
               | hebrew).
               | 
               | However, their metric was IIRC "within 3 days of first or
               | second dose"; so 6 days worth of myocarditis compared to
               | your full year number, so a factor of 60 (assuming
               | uniform distribution over the year) to put on same scale.
        
               | Pyramus wrote:
               | Not disagreeing with your general message regarding
               | individual risk assessment based on age, sex, health etc.
               | What I will say though is that you seem to be comparing
               | to the baseline scenario "Covid stops spreading".
               | 
               | After one year of Covid (and its mutations) that baseline
               | simply doesn't exist (any more). Instead we are in a no-
               | win situation:
               | 
               | (a) We keep lockdowns/non-pharmacological measures and
               | border closures,
               | 
               | (b) We let Covid spread slowly,
               | 
               | (c) We vaccinate.
               | 
               | Each scenario has associated cost. Now back to your
               | point:
               | 
               | > But because everyone gets vaccinated, we require
               | exceptional proofs of safety.
               | 
               | Safety is neither binary (exceptional/not exceptional)
               | nor absolute and _always_ relative to Covid. Each and
               | every vaccine up to now is orders of magnitude safer than
               | Covid for the vast majority of people (YMMV!).
               | 
               | Not an expert, but what's even more interesting is that
               | among the already very few severe side effects, even
               | fewer are due to the 'vaccine ingredients' (e.g. allergic
               | reactions incl. blood clots) and many are conjectured to
               | be due to the 'SARS-Cov-2 ingredients' (e.g.
               | myocarditis). Heuristically speaking you can choose
               | between Covid or a very very very mild version of Covid.
        
               | beagle3 wrote:
               | No, I'm not comparing to "covid stops spreading", but I'm
               | also not assuming (as you seem to be) "everyone will
               | eventually get it in the way whoever got it so far got
               | it".
               | 
               | > Each scenario has associated cost.
               | 
               | There are other scenarios, e.g.
               | https://www.ox.ac.uk/news/2021-02-09-common-asthma-
               | treatment... shows a cheap widely available steroid
               | inhaler has comparable efficiency to vaccines in the KPIs
               | studied by the Pfizer trial. I'm not saying it should be
               | used _instead_ of a vaccine; but it 's also not true that
               | your list is close to exhaustive. We keep finding out new
               | stuff. In the first 2-3 months, the
               | intubation+ventilation regime was counterproductive; it
               | took a while to realize, but now we know that. We also
               | know (e.g. from Florida and Texas) that the NPI are much
               | less effective than they were assumed to be.
               | 
               | > Each and every vaccine up to now is orders of magnitude
               | safer than Covid for the vast majority of people (YMMV!).
               | 
               | That's ... not been shown. The Israeli study I linked to
               | above (a report of it) says this assertion might be wrong
               | for Pfizer for the sizable group of 16-30 ; The British
               | think that's not true for AZ under age 30 ; many
               | countries in the EU think that's not true for AZ under
               | the age of 50 ; Norway thinks that's not true for frail
               | elderly.
               | 
               | And basically, we only have short term safety data
               | (pfizer: less than a year for 20K people, less than 6
               | months for the rest), so even if it is true that "every
               | one will eventually get it", it does NOT follow that it
               | makes sense to vaccinate everyone right now -- if it
               | takes 20 years until "everyone eventually gets it", and
               | severe side effects appear 2 years later, then, no, it
               | doesn't make sense.
               | 
               | I linked a BMJ+Science article that showed for a
               | similarly EUAd vaccine, "Pandemrix" in 2009 that it took
               | over a year to figure out that it was causing narcolepsy
               | and worse than the flu it was supposed to stop. It's not
               | just a theoretic possibility - it happened in a very
               | similar setting just 11 years ago, and the causes are NOT
               | perfectly understood to the point that you can guarantee
               | it won't happen again.
               | 
               | > many are conjectured to be due to the 'SARS-Cov-2
               | ingredients' (e.g. myocarditis). Heuristically speaking
               | you can choose between Covid or a very very very mild
               | version of Covid.
               | 
               | You could be right, but that's not at all clear. This
               | paper from Nature Immunology
               | https://www.nature.com/articles/s41590-020-00808-x.pdf
               | shows that 80% of unexposed people have a T-cell response
               | to SARS-Cov-2 - that is, they have cross-immunity.
               | 
               | It could be that for those 80%, that response would be
               | enough to stop the virus before it can get systemic
               | traction, whereas the vaccine is essentially guaranteed
               | to generate systemic effect. I asked an immunologist, who
               | said he doesn't know the answer and does not believe
               | anyone does without measuring.
        
               | lamontcg wrote:
               | The rate of MIS-C in children is on the order of 1 in
               | 20,000. So acute myocarditis (which goes away and does
               | not produce lasting damage) at that level is entirely an
               | acceptable risk.
               | 
               | You're under the impression that either the vaccine must
               | be perfectly safe and/or that the disease is perfectly
               | safe for young people. Both of which are false.
        
               | beagle3 wrote:
               | I don't know how you read that into what I wrote.
               | 
               | It doesn't have to be perfectly safe; but it has to be
               | significantly safer if you get it, than the disease if
               | you get it -- which is, in fact, the case for all
               | regularly administered vaccines (MMR, polio, tetanus,
               | etc.), and comes with a warning and explanation for those
               | that aren't (our pediatrician made sure we understand the
               | rotavirus vaccine before we gave it to our child (we did)
               | especially _because_ it 's safety profile, while still
               | good, is not as good as the MMR and polio ones.
               | 
               | MIS-C is a big discussion that I don't have enough time
               | for, but according to https://www.cidrap.umn.edu/news-
               | perspective/2021/04/new-find..., incidence in the US is
               | 1:50,000. Acute myocarditis often goes away with no
               | damage but not always. MIS-C does too.
               | 
               | And it's not even clear yet if any vaccine will stop
               | MIS-C, so -- no, it's not an entirely acceptable risk.
        
         | busyant wrote:
         | This is a legitimate question, so I don't know why it's being
         | downvoted. Especially given the statement in the abstract of
         | the paper that says, "We show here that S protein alone can
         | damage vascular endothelial cells (ECs) in vitro and in
         | vivo...."
         | 
         | That being said, other people on this thread have provided
         | reasonable mechanistic explanations as to why the vaccines
         | would not have this effect, but I will also add we have
         | _empirical_ evidence that the vaccine does not impair
         | endothelial function (or at least it is extremely rare) because
         | we have millions of people who have received the vaccine
         | without impaired endothelial function.
        
           | dcow wrote:
           | My partner developed inflammation (resembling gottron
           | papules) on her knuckles a few weeks after receiving the
           | first moderna dose. She now (few days later) has developed a
           | shoulder rash where the vaccine was injected. It's very
           | curious.
        
             | IAmGraydon wrote:
             | Someone I work with (female, 25 years old) had inflammation
             | on her knuckles that is similar to what you describe. This
             | was after her second shot - not sure if it was Moderna or
             | Pfizer, but it was MRNA. She's fine and it eventually went
             | away, but it's certainly interesting. She doesn't have any
             | autoimmune disorders that she knows of.
        
               | Gibbon1 wrote:
               | The vaccine appeared to piss off the RSI in my right arm
               | for about two weeks. I would have gotten the shot in my
               | left arm if I knew that was going to happen.
        
             | christkv wrote:
             | I've also not seen any studies about side effects in people
             | who already had the virus before getting the first dose.
        
             | lc9er wrote:
             | My spouse, who suffers from an autoimmune disorder,
             | suffered similar symptoms. Severe enough that she won't be
             | able to get the second dose. My understanding (from her
             | doc) is that this is a known, but uncommon side effect for
             | people with autoimmune conditions.
        
               | podgaj wrote:
               | Just sayin'
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793296/
               | 
               | The data presented in our work, although very
               | heterogeneous in the manner of collecting and
               | investigating samples, have proved to be extremely
               | consistent in witnessing a deficiency of zinc in serum
               | and plasma of patients compared to controls.
        
               | treeman79 wrote:
               | Does get the uncommon side effects of medication much?
               | 
               | Have an autoimmune, and I get most of the rare side
               | effects of medications.
        
               | lc9er wrote:
               | Constantly. Her list of banned medications is huge. Each
               | time she's prescribed a medication, she has to decide if
               | the "rare side effects" are worth risking or are worse
               | than going untreated.
        
             | sroussey wrote:
             | I had a red area after the second shot on my shoulder, and
             | so did my family members including cousins in other states.
        
             | sebmellen wrote:
             | Quite strange. I've had almost the exact same skin-level
             | reactions, only I received the BioNTech/Pfizer vaccine.
        
         | rolph wrote:
         | this is a relevent question, the difference between the two
         | cases, is that the virus is mobile and has opportunity to
         | travel through the entire endothelial tissue structure,
         | interacting with many molecular types and situations
         | 
         | the vaccine causes a small volume of stationary cells in the
         | muscle mass of the shoulder to express the S protien on the
         | surface, staying in place but providing signal to the immune
         | system
         | 
         | [adndm] keep in mind the virus replicates, inside you, the
         | vaccine doesnt, and the vaccine stays where you put it, it
         | doesnt spread out everywhere that has a receptor
        
           | _greim_ wrote:
           | Interesting. Is there a significant difference in total
           | number of viral particles versus vaccine particles your cells
           | are exposed to, over the course of the infection/vaccination?
        
             | rolph wrote:
             | in general terms yes, there is no real hard number on
             | minimal number of viral particles required to result in
             | infection, its most likely a small number compared to the
             | number of vaccine particles in a dosage. assuming 30
             | micrograms dosage in a volume of 300 microliters that is a
             | very large number of particles in one place. this is not a
             | lot of vaccine, but this [30micrograms] would be quite a
             | lot of viral particles.
             | 
             | something to keep in mind is the fuzz of biological
             | systems. molecular processes can have more than one outcome
             | but there is a general bias toward an overall stability, so
             | when a vaccine is produced, there is a certain amount of
             | fuzz to it in the form of particles that dont assemble
             | correctly or ar otherwise non desireable, processing the
             | vaccine keeps these characters to a minimum.
             | 
             | the same thing happens to the virus, the fuzz portion being
             | in someway unable to replicate or enter a cell, just out of
             | the way the fuzzy dice roll.
             | 
             | so its hard to pin down a number of minimally effective
             | dose for either case, however virus amplifies past the
             | original dose, and spreads to mutiple locations, signaling
             | any molecular system that can be bound to, in this case
             | vast preference being given to ACE-2, resulting in
             | perturbation of the RAS system and the now stereotypic
             | covid symptoms
             | 
             | so viral particles amplify over time, and over a spatial
             | distribution, vaccine particles stay in site and dont
             | replicate and dont migrate to interact with other cells in
             | the tissue or throughout the body.
        
         | hourislate wrote:
         | Disclaimer: I am not qualified to interpret this study and have
         | no experience in this field.
         | 
         | So the study indicates that the Spike Protein binds to ACE2
         | that is found in the membranes of cells located in the lungs,
         | arteries, heart, kidney, and intestines, and down regulates
         | them to the point where it damages your mitochondria in those
         | organs. So according to the research they did, it's not just
         | the virus that can hurt you but the mechanism (Spike Protein)
         | the virus uses to attach to your cells and replicate that can
         | cause this damage.
         | 
         | It is likely that the vaccine itself which holds the mRNA and
         | not the actual Spike Protein or Virus (just the instructions on
         | how to make the Spike Protein) is administered in a
         | intramuscular area of the body (Shoulder Area), never able to
         | live long enough (mRNA dies off quickly) to enter these areas
         | where ACE2 is found (Heart, Lungs, Kidneys, etc). The muscle
         | tissue/cells in the upper arm create some Spike Protein and
         | your immune system basically say WTF is that and kills it long
         | before it can ever reach these organs or areas of the body.
         | 
         | The real Virus typically enters the body through the nose and
         | mouth and heads directly into the sinuses and can spread very
         | quickly to lungs and then move on from there into other organs.
         | If you're someone who is one of the folks (Metabolic Disease,
         | severe autoimmune dysfunction) who might be susceptible to what
         | this study suggests, the vaccine is the way to go since it
         | might give you a better chance to avoid the negative outcome
         | from the Spike Protein affecting ACE2 and then damaging the
         | mitochondria in your Organs cells.
        
           | molticrystal wrote:
           | >is administered in a intramuscular area of the body
           | (Shoulder Area), never able to live long enough (mRNA dies
           | off quickly) to enter these areas where ACE2 is found (Heart,
           | Lungs, Kidneys, etc)
           | 
           | We know to where it typically tends to go now, "the muscle
           | tissue at the site of injection, the lymphatic tissue
           | downstream in your armpit on that side, your spleen, and (for
           | the first day or two) your liver. " [0]
           | 
           | [0]https://blogs.sciencemag.org/pipeline/archives/2021/01/21/
           | mr...
        
         | tmabraham wrote:
         | A good question, one of the paper's authors had the following
         | responses on Twitter:
         | 
         | https://twitter.com/manorlaboratory/status/13887170085444198...
         | https://twitter.com/manorlaboratory/status/13887291512893153...
        
           | karaterobot wrote:
           | First tweet:                   i'm going to give a full
           | response asap. but quickly for the record:         1) the
           | (relatively) small amount of spike protein produced by the
           | mRNA vaccine would not be nearly enough to do any damage
           | 2) i happily got the mRNA vaccine, FWIW         3) i
           | encourage everyone to get it
           | 
           | Second tweet:                   a couple prelim responses to
           | anti-vaxxers misrepresenting these findings (here: https://tw
           | itter.com/manorlaboratory/status/1388717008544419843?s=21).
           | tl;dr: mRNA vaccine is waaaaay safer than COVID19 and
           | everyone should get it - I did and everyone in my family did
           | as well! Our paper just shows this disease really sucks.
        
       | morsch wrote:
       | "Endotheliitis is an immune response within the endothelium in
       | blood vessels, in which they become inflamed. The condition can
       | cause oedema of the surrounding tissue, including the stroma, and
       | can cause irritation and pain. If it is within the cornea, it can
       | result in permanent loss of vision. The condition can be caused
       | by a number of factors, such as mumps and cytomegalovirus under
       | certain circumstances." (Wikipedia)
       | 
       | And, as to the first question that came to my mind, from the
       | paper: "Collectively, our results suggest that the S protein-
       | exerted EC damage overrides the decreased virus infectivity. This
       | conclusion suggests that vaccination-generated antibody and/or
       | exogenous antibody against S protein not only protects the host
       | from SARS-CoV-2 infectivity but also inhibits S protein-imposed
       | endothelial injury and ultimately decrease cardiovascular
       | complication-associated mortality in COVID-19 patients."
        
         | [deleted]
        
         | treeman79 wrote:
         | My blood vessels get inflamed now and then. In Sjogrens world
         | it's known as a "flare"
         | 
         | It's horrifically painful. There is no sympathy from anyone
         | since you look normal.
        
           | dathinab wrote:
           | You have our sympathy, I think there are enough of us here
           | which known that looking fine doesn't mean being fine.
        
           | Sudophysics wrote:
           | :(
        
       | Alex3917 wrote:
       | Yeah we've known this for over 10 years, zero surprise here.
       | There were literally popular books written saying that this would
       | be the mechanism of action for novel coronavirus pandemics (and
       | how to treat them) years before the current pandemic even
       | started, e.g.:
       | 
       | https://www.amazon.com/Herbal-Antivirals-Remedies-Resistant-...
       | 
       | Here is the direct quote from the book, published in 2013:
       | 
       | "Once receptors on these cells are compromised there is enhanced
       | vascular permeability, increased lung edema, neutrophil
       | accumulation, and worsened lung function. In essence, once the
       | virus begins attaching to ACE-2, ACE-2 function begins to be
       | destroyed. ACE-2 function also tends to be less dynamic as people
       | grow older, hence the more negative the effects of SARS infection
       | on the elderly. [...] ACE (in contrast with ACE-2) inhibitors
       | increase the presence of ACE-2 and help protect the lungs from
       | injury."
        
         | Blackthorn wrote:
         | Yes, that's why they went looking to verify that hypothesis and
         | lay out the mechanism that the virus acts...
        
         | darkhorn wrote:
         | So, some people were studying new kinds of viruses?
         | 
         | Oh, okay, yeah, here
         | https://www.wired.com/2013/05/h5n1-h1n1-reassortment/
        
         | justicezyx wrote:
         | Is this Amazon book on herbal effects real? I am pretty
         | familiar with Chinese traditional medicine, but their
         | effectiveness is very dubious.
         | 
         | The author does not look like a medical professional either.
        
           | jpxw wrote:
           | It's unscientific nonsense, don't waste your time.
        
         | dctoedt wrote:
         | Not my field (I _can_ spell DNA) but this recent piece seemed
         | of interest. FTA:  "A large meta-analysis provides yet more
         | evidence that ACE inhibitors and angiotensin receptor blockers
         | (ARBs) pose no harm to patients with COVID-19 and may even be
         | associated with protective benefits, particularly in patients
         | with hypertension."
         | 
         | https://www.tctmd.com/news/continue-ace-inhibitorsarbs-covid...
        
           | Alex3917 wrote:
           | Also women and smokers are underrepresented among
           | hospitalized patients, which was the first confirmatory
           | evidence from over a year ago.
        
             | piva00 wrote:
             | I know nothing about physiology (apart from up to high
             | school level, so... Nothing), could you expand on how
             | smokers and women relate to ACE-2?
        
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