4 years ago by morsch
"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."
4 years ago by treeman79
My blood vessels get inflamed now and then. In Sjogrens world itās known as a āflareā
Itās horrifically painful. There is no sympathy from anyone since you look normal.
4 years ago by dathinab
You have our sympathy, I think there are enough of us here which known that looking fine doesn't mean being fine.
4 years ago by stjohnswarts
I had a friend with that. The flares could have her basically out of action for a month or more as she was IT and found it impossible to work during those times.
4 years ago by Sudophysics
:(
4 years ago by undefined
4 years ago by stevemk14ebr
Can someone ELI5 please? My field is low level computer systems, and unfortunately that knowledge does not extend to low level physiological processes!
4 years ago by 908087
Don't let that stop you from pretending to be an expert in other fields. It doesn't stop anyone else here.
4 years ago by Alex3917
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."
4 years ago by dctoedt
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...
4 years ago by Alex3917
Also women and smokers are underrepresented among hospitalized patients, which was the first confirmatory evidence from over a year ago.
4 years ago by piva00
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?
4 years ago by Blackthorn
Yes, that's why they went looking to verify that hypothesis and lay out the mechanism that the virus acts...
4 years ago by justicezyx
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.
4 years ago by jpxw
Itās unscientific nonsense, donāt waste your time.
4 years ago by darkhorn
So, some people were studying new kinds of viruses?
Oh, okay, yeah, here https://www.wired.com/2013/05/h5n1-h1n1-reassortment/
4 years ago by unanswered
If this is a function of the spike protein, doesn't that mean the mRNA vaccines cause this effect as well?
4 years ago by busyant
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.
4 years ago by dcow
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. Itās very curious.
4 years ago by lc9er
My spouse, who suffers from an autoimmune disorder, suffered similar symptoms. Severe enough that she wonāt 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.
4 years ago by IAmGraydon
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.
4 years ago by christkv
I've also not seen any studies about side effects in people who already had the virus before getting the first dose.
4 years ago by sebmellen
Quite strange. I've had almost the exact same skin-level reactions, only I received the BioNTech/Pfizer vaccine.
4 years ago by rolph
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
4 years ago by _greim_
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?
4 years ago by rolph
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.
4 years ago by hourislate
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.
4 years ago by molticrystal
>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...
4 years ago by unanswered
The funny thing is that list of places the mRNA gets to does not have any overlap with my list of "places in my body where I want SARS-CoV-2 spike protein".
4 years ago by tmabraham
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...
4 years ago by karaterobot
First tweet:
iām 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
a couple prelim responses to anti-vaxxers misrepresenting these findings (here: https://twitter.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.4 years ago by russfink
Would someone please dumb this down for me?
4 years ago by collyw
The spike protein alone can cause damage, in other word you don't need a coronavirus infection. The vaccines make your body generate this protein.
4 years ago by podgaj
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?
4 years ago by jm4
When I was hospitalized for covid, they were giving me zinc (among other things) every day.
4 years ago by podgaj
Yes, Iāve already known about that. Iām just wondering why theyāre not checking peoples zinc levels or why theyāre not recommending people supplement with zinc.
The rate of zinc deficiency in India is near 50%!
4 years ago by nradov
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...
4 years ago by podgaj
Yeah yeah yeah, but why isnāt this been blasted with the public airwaves, especially in India?
Plus, theyāre giving zinc to people already sick. Why not check people for zinc deficiency and supply them with the zinc they need? I know why, itās because we donāt believe in preventative care in this country.
4 years ago by nradov
Yes it is disappointing how public health authorities have focused almost entirely on exposure prevention. There should be equal focus on harm reduction for people who do get exposed.
4 years ago by collyw
Proponents of hydroxychloroquine have been saying that it needs to be taken with zinc to be effective.
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