CharonY

His comment is uninformed. There is nothing in the spike protein mRNA that makes it vastly more stable, and the instability of mRNA is well known. It is fairly common to use surrogates for these type of studies. Even if it was much more stable, we would be looking at a couple more days at best, which, unless you are talking about mayflies rarely falls under the moniker of long-term effects. I just quickly calculated the total detectable lipid concentration, which dropped by that amount. So yes, it is cumulative for all organs. Again, it is based on how we generally metabolize lipids. As we are not getting continuous injections, what happens is that the total amount of lipids gets distributed and eventually eliminated. We also know which organs conduct much of the lipid metabolism so I am not sure why at this point we should all pretend not to understand how lipid metabolism works. Again, I think the basic thing that you and the twitter post seem to misunderstand is how compounds, including lipids get metabolized and eliminated. I am sure that if you look at ADME profiles, you will find something for those LNPs. Moreover, the post seems to be confused about how elimination studies are done. If you want to understand how it is eliminated from the body you would go and measure generally blood and liver values as well as identify those compound in waste (i.e. urine and feces). And guess what, that is what they did and how they estimate elimination rates (some other routine methods involve simple blood plasma analyses. Quickly screening lit has indicate that terminal terminal half life for ALC-0315 and ALC-0159 were ~3 and 8 days, respectively. It is not a hypothesis, it is how the liver works. It is how we metabolize things. What you propose is that for some reasons LNPs changes how our organs work. If the liver would simply accumulate harmful substances we would be all dead. A steady state also does not see-saw. If the compound was delivered at a steady rate the concentration would remain steady and then decline slowly as the compound is being eliminated. However drugs can be released in bursts or re-distributed unevenly (e.g. the compound can be released from other organs back into the bloodstream). The main source in this case is leakage from the injection site into the bloodstream. Again, not a hypothesis, there is huge body of literature out there showing how liposomes, LNPs and similar compounds pass through our body, get eliminated and/or can get modified to control said elimination. We should not assume that science collectively forgot how basic animal physiology works just because a random guy on twitter doesn't. Again, there are plenty of studies looking at mRNA as well as LNP degradation and metabolization, as well as basic liver functions. And I want to recall that one of the biggest challenges mRNA vaccines faced are the fact that those were eliminated too quickly to reliably create an immune response. Similarly, early LNPS were cleared too rapidly which added to the issue. Thus, much of the work surrounded stabilization of mRNA in vivo. So suddenly assuming that it is somehow very stable just goes against all the basic biochemistry we understand regarding those molecules. In addition, the whole molecule is not terribly stable outside of the body, either, which is why they require storage at low temps. I am not sure why you want to discuss tweets from a person who clearly has no expertise on that matter. Although it does not fall strictly into my area of expertise either, it is easy to see that the author of the tweet has not found it necessary to educate themselves on the subject matter before taking it to the social media (and yes, the irony is not entirely lost on me, considering my postings here). Take Gregoriadis and Neerjun (https://doi.org/10.1111/j.1432-1033.1974.tb03681.x) which is one of the early papers looking how one could control uptake and elimination. There are tons of advances to control elimination rate, tissue specificity and overall stability in the lit, with detail that goes far beyond my knowledge. So any argument that argues that something mysterious is happening here, is likely based on ignorance. So what I think you propose is that for some reasons the main organs for lipid metabolization (and subsequent elimination) will only be active for the first two days or so, then all residual LNPS would magically bypass these organs and mechanism, accumulate in ovaries and stay there forever? So instead on measuring well known excretion routes we should instead focus on something that a random twitter guy does not understand? I would advise you look for some reliable sources. I am not sure whether the person has an agenda or is just badly misinformed, but either way I would urge you to find someone better to follow as neither of us is going to learn anything by feeding trolls.

! Moderator Note Does not seem to discuss mainstream biology, moved to speculations. Please take some time to familiarize yourself with the rules regarding speculation threads. https://www.scienceforums.net/forum/29-speculations/#elForumRules

Vaccinated folks are less likely to get infected from the virus in the first place, and even if infected they overall viral load tends to be lower. I.e. they produce fewer particles and the overall (population-wide) reservoir of viruses that could mutate is lower.

I have addressed the issues for the most part above already but I can give a more detailed breakdown for clarity. Overall I do not think that the tweet is well informed (but then so are most, I guess). 1) the mRNA in the vaccine is fragile and we know that it degrades over time. In the Pfizer report we see that the test mRNA they used vanished from the liver within 48 hours. In other words, if we expect effects due to the mRNA, they would need to happen before that time frame, and likely need to involve a higher accumulation than in the liver (as liver inflammation does not seem to be a major issue). 2) it can be expected that the LNP and their load seep out from the injection site, and typically eventually reach the liver. Over time, they would be metabolized and eliminated from the body. The Tweet seem to claim that the liver values are stable but that is not necessarily what we expected. Rather we have steady state situation where elimination is balanced with additional accumulation (i.e. likely the liver is doing its work). In fact, between say hour 2 and 48 h we see a loss of ~30% of the total signal. I.e. even if distributions shift, the total levels will obviously go down, rather than up. As such, very long term effects are unlikely to happen due to accumulation of stuff. If anything happens it is more likely due to something stupid our immune system is doing that could affect the body long-term. 3) We see that much of the short-term accumulation happens in the liver (which again, does most of the lipid metabolism) but also spleen (same reason), each of which have about double the concentration than ovaries. The other site to look for for short-term effects (again the mRNA is gone pat 48 hours) could be e.g. also adrenal glands, where quite a bit accumulates in the 24 hours but I have not seen reports that indicate issues here (again, the issue with endpoints, I outlined above). 4) The kinetics are likely going to be different. The rats got a 50 ug dose whereas the Pfizer/BioNTech vaccine is about 30 ug (IIRC). Given that the average human weighs about 240 times more, the elimination is likely going to be faster. There are a couple of other points I could point out, but I hope that this explains most of it (and let me know if something is unclear (as often I am in a rush and did not proofread it properly).

! Moderator Note Post regarding effects of vaccines have been split from another thread.

Also the cohort has more men, IIRC. That part also means that in the FAIR study the symptoms are those that are bad enough to warrant a claim (i.e. severe symptoms). I.e. one could say that about 23% of all COVID cases (including folks initially without symptoms) had issues that were severe enough to warrant a claim. The study in OP was looking for typically COVID-19 associated symptoms, such as loss of smell/taste, which won't typically appear on claims, but can still affect quality of life. But there were also other symptoms in lower proportions such as dyspnea as well as neurological symptoms other than loss of smell. It should be noted that post-viral syndromes are not new or unique to COVID-19. But often general malaise and other quite possibly crippling long-term effects are often not recognized as folks may not associate them with a prior infection. Many folks are not getting tested when they have flu-like symptoms, for example.

Not sure what you mean. We have plenty of diseases that have a significant burden on public health. Influenza is responsible for 10k deaths in France. Covid is likely to add to it but it is not the first nor will be the last.

Actually I don't think we can easily establish that either. The FAIR study does not have a control group to establish how many of such claims are made by COVID-negative populations. However, the veteran's study for example looked especially add the increased odds of such symptoms in negative vs positive groups (with the caveat that veterans are not a truly representative group for the broader population).

If vaccination is the only measure then SARS-CoV-2 is likely to stick around (we have got another thread about that here somewhere). Fundamentally our most likeliest point of stamping out the disease was early in the pandemic, or around the summer time when we had a reduction in many areas to more manageable levels. Of course we decided to open up at that point... Now, the hope is that with vaccination the virus will be more manageable like other disease outbreaks that we deal with. What we do not know yet are things like overall health burden, especially if we take long-haul symptoms into account.

Note that the data in OP looks specifically at a particular age group, whereas the values that I (and you) have indicated are for the whole study group, separated by symptoms. As such the data is actually very worrisome, as the age group was assumed to be least affected, but shows above average risk with regard to long-term COVID. I have not looked at the other data in an age-distributed way, but I would be curious to see how that looks like.

There is another study using large number using large number of insurance claims showing that ca. 23 % of all; 19% of asymptomatic, 27.5% of symptomatic but not hospitalized and 50% of hospitalized patients show long-covid symptoms (I remembered the numbers wrong, my apologies. LINK Another study using data from the veteran's health affair to come to similar conclusions: High-dimensional characterization of post-acute sequelae of COVID-19 | Nature Post-viral syndromes are insidious as they were often not recognized (there is more recognition now) but there are limited treatment options. Especially in this case it appears that it is unclear in some cases whether the symptoms actually eve go away (especially the neurological issues). With increasing vaccinations and decreasing active cases there is an increasing worry about these issues. While one might hope that the vaccines may also be protective against long-haul issue, but I have not seen data on that yet.

Yes, that is basically the most likely scenario.

I think the odds that we mess up the planet to such a degree that only a fairly small human population survives and where much of the effort is focused on sustenance (albeit in a high-tech version) is also not completely off the table.

LNPs were in use before that. See Anselmo and Mirtagotri Bioeng Transl Med. 2016 Mar; 1(1): 10–29.

We have to separate the issues. If we talk about the current vaccine, there are two factors that are relevant. The first is the availability of other vaccines and the respective countries seem to have sufficient access to cover their population with these vaccines. And the second is that currently B.1.617.2 (delta) is becoming dominant in many areas and AZ seems to perform worse than the others. Given the overall risk data, if there was no other vaccine, I would still take the AZ, even if I was in a risk group. Going to adenovirus-based vaccines and therapeutics, I should add that, again, almost everything we put in our bodies does something to it and especially when applied to a large population it is almost inevitable that there will be rare harmful interactions. The goal is therefore not zero events, but to ensure that the overall benefits outweigh the risks for a given population. Moreover, it is important to note that interactions that can lead to harmful events are not the same thing as the harmful event itself, there are mitigation strategies, dosage effects and so on. For example aspirin, causes blood thinning and in theory that could lead to internal bleeding. However, at recommended dosages it is considered to be safe, except for certain folks. In the past some studies indicate that certain adenovirus-based vectors might bind to circulating platelets and getting sequestered. That actually leads to reduced platelet count but not necessarily to clots alone. For that, it has been suggested that the vaccine might form an antigenic complex with platelet factors, resulting in the formation of antibodies against that complex. These antibodies than activate the platelets and initiate a pro-thrombotic response. It is not really my field so I do not know who would be at higher risk for this event and why.

Most of the things in the post have been debunked in the past. There is only a small group of researchers (Lynn, Rushton and similar folks) who are still in the camp of strong gender differences. However, most other groups have failed to reproduce such results. What folks have found instead is that for the most part brain dimorphisms do not exist. If one takes a random brain, no one can really predict with any accuracy whether that brain is male or female. The last bastion of these studies are MRI-based, which generates high-dimensional data and allows the distinction of even miniscule differences. On the flip-side we run into statistical issues such as overfitting, which are a common problem with using this kind of data to identify differences (and note, even if we find statistically significant differences in certain areas, it does not necessarily allows us to accurately predict whether a given brain is male or female, the difference would also need to be large enough to make that distinction). However, even MRI fails to be reliable indicator (see David et al. Scientific Reports volume 8, Article number: 6082 (2018) for a discussion on reporting bias). A recent meta-analysis ( Eliot et al., Neuroscience & Biobehavioral Reviews Volume 125, June 2021, Pages 667-697), the largest of its kind, failed to identified the dimorphisms speculated to exist. In other words, even if the most sensitive means to look at the brain fails to see clear differences, all the wild speculations in the post about these presumably huge gender dimorphisms and then the wild extrapolation regarding to performance are pretty much moot.

This is true for most medications that are not taken long-term.

Before I talk a bit more on the study itself I want to take a step back and talk a bit how risks in medical interventions are generally evaluated. The key element here is monitoring certain clinical endpoints, including efficacy of the drugs but also specific indicators of morbidity, for example. In a more general sense, there are no "no effect" endpoints. If you eat a cheeseburger, for example, I could monitor increases in negative biomarkers in your blood, there could be short term shifts in the gene expression of you gut microbiota and so on. However, that tells us little about the risks. As such it would be better to use endpoints such as heart attack and stroke rates and so on. The big issue with long-term effects is that it becomes very difficult to figure out what the causes for a given hard endpoint are, which is why for example nutritional studies, which often are long-term, often do not have clear outcomes. Trials are looking at such outcomes and from that viewpoint the current the current vaccines are no different from other vaccines or therapeutics. You look at endpoints within a given time frame for a given sample size. The SARS-CoV-2 vaccines all fulfil pretty much the same requirements as you typically do not monitor individuals indefinitely after taking a medication. So as such, we can be fairly certain that the the the mRNA vaccines do not seem to have any acute effects and we know roughly as much about long-term issues as for other medication. So what is new regarding our knowledge about concerns regarding this specific vaccine? One risk that folks were concerned years back is the risk that the LNP could distribute their payload throughout the body and enrich in the liver. If the spike protein is formed there, it could result in local inflammation of the organ and liver damage. However, this does not happen. In fact, the Japanese report indicates why, within a relatively short time frame all the mRNA expression is basically gone. So what about the LNP alone? Again, you get a dose, the lipids move through your body and get metabolized. Typically they accumulate in adipose tissue or liver (which for some reason is not plotted, it is higher there than in ovaries, for example). So does this cause harm? The cited study on direct injection of pure LNP indicate that yes, if given in high concentrations they can cause inflammatory responses. However, this itself is not an indicator for adverse health effects. In fact, the paper argues that these inflammatory responses might be why the current mRNA vaccines are so effective (which was a big worry before, the fact that mRNAs are generally not very immunogenic). I.e. the local inflammation caused by LNPs could have been beneficial for efficacy reasons. We do see lower efficacy in the other vaccines, for example. While the study is helpful to highlight the potential to elicit inflammatory responses from LNPs alone, (and therefore nasal delivery is not a good idea) it does not actually suggest health issues. Again, it is about endpoints and what the study measured is not helpful to provide evidence of harm in humans. First, mice are not a a great model for immune responses in humans (which is a common issue with animal models) and second, they injected a very high amount- 10 ug, IIRC which is a huge amount compared to their body weight relative to the amount found in vaccines and the body weight in humans (we are talking over a thousand fold at least if I got my numbers right). Moreover, as you know you only get two injections, so there is no chance for long-term accumulation (as opposed to many of the chemicals we use in personal care products, for example). Thus, if inflammation caused by LNPs resulted in adverse effects you would expect to see most the effects fairly soon (within days) of injection, as the levels after that will gradually decline (rather than increase). The precise rate is not known as they only monitored for two days, but it won't be years. What we do know and expect are inflammation, which are common with most vaccines (as inflammation is the result of the immune system reacting). Mild myocardial inflammation has also been recorded which could be related to LNPs (or the vaccine in general). But again, the endpoints do not suggest significant adverse health effects. Blood clots do not seem to be different between unvaccinated and Pfizer/Moderna vaccinated folks, but seem elevated in certain population subsets in AstraZeneca vaccines, which is likely to related to the adenovirus used (there have been reports in the past for issues with certain adenovirus-based vaccines, but I am not sure what they were in detail and in any case, they are not related to mRNA-based vaccines such as Pfizer/BioNTech. Meanwhile, there are studies (e.g. https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/A Detailed Study of Patients with Long-Haul COVID--An Analysis of Private Healthcare Claims--A FAIR Health White Paper.pdf) showing that even asymptomatic patients might be at risk of having long COVID symptoms, though it is still about double as high in symptomatic patients. So again, we have a vaccine that might cause issues in some folks, but protects them from much bigger harm. And on top, they also protect those that are too stubborn to protect themselves.

4 pages and 10 years. If anything it shows how persistent stereotypes are.

I think to some degree the points are valid, but may also somewhat overplay the uniqueness of humans. While we often describe a given species to behave in a monolithic way, many folks interacting a lot with higher animals report a huge range of behavioural differences. Of course there is more behavioural modulation (learning/training) going on in humans but I would almost make the reverse argument, that we simplify animal behaviour too much.

As I and other have said, the premise is clearly wrong. There is a huge disparity between rich and poor Muslim countries as there are between Christian countries. Trying to find a singular explanation for someone that does not exist in the presented form is a fool's errand.

Yes, if you ignore age-related issues, there are no age-related issues. There is also a range of increased risk (in terms of morbidity and mortality) for the mothers starting around age 35.

That is a) not true and b) is moving the goal post. But overall acknowledging that there are more factors is what my basic comment alluded to. Wealth of a country is not based on singular factors, but depends on many aspects. Including access (but also sovereignty over resources). The simplified narratives as used in the original OP do not do the complexity of the region. This was mostly true in Germany until rather suddenly it wasn't, for example. And again, your comments are also factually wrong, considering that the country you outlined have lower health indicators than many Arabic speaking countries. Edit: Crossposted with other with similar comments.

I think folks in the first page of this thread have already highlighted that this not true. In terms of GDP per capita some of the richest countries in the world are Arab countries.

I am really sorry for being that pedantic, but I would like to point out that "three" in German is "drei". It is one of the weird differences between English and German and a bit of a pet peeve of mine (same with "stein" vs "stien"). I can live with the umlaut thingy but the the other thing just scratches at my soul (which basically means I spent too much time in Germany).