Laboratory evidence of Antibody Dependent Enhancement. But there's a twist.

[as_rocketman]

Published last week in PLOS One, researchers at the University of Arkansas for Medical Science believe they've found a link between "long COVID," or PASC, and a particular antibody. However, this so-called autoantibody develops during natural infection, not following immunization.

We hypothesized that autoantibodies against ACE2 may develop after SARS-CoV-2 infection, as anti-idiotypic antibodies to anti-spike protein antibodies. [...]

None of the 13 patients without history of SARS-CoV-2 infection and 1 of the 20 outpatients that had a positive PCR test for SARS-CoV-2 had levels of ACE2 antibodies above the cutoff threshold. In contrast, 26/32 (81%) in the convalescent group and 14/15 (93%) of patients acutely hospitalized had detectable ACE2 antibodies. [...]

These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.

The basic idea here is that when fighting infection, your immune system is stimulated to develop new antibodies against the antigens it sees. At first this largely includes the Receptor Binding Domain of the virus. But over time, this also includes the complex formed by the RBD and a bound ACE2 receptor. There is also the "anti-idiotypic" antibody that is literally a mirror image of the first antibody, sometimes helpful in suppressing a matching antigen -- but sometimes leading to autoimmune disease. These mechanisms produce a second wave of autoantibodies that recognize ACE2 itself, causing suppression of ACE2 and leading to overall immunosuppression.

The dataset is small but shows a striking difference between different populations:

Antibody against the SARS-CoV-2 RBD was present in 93% of the Inpatient+ group and 97% of the Convalescent+ patients but in only 40% of the Outpatient+ group and none of the patients in the Outpatient- group. Antibody against ACE2 was present in 93% of Inpatient+ and 81% of Convalescent+ patients but was below the cutoff value in all but one of the Outpatient+ and all of the Outpatient- group. [...] These data indicate that development of SARS-CoV-2-specific antibodies correlates with the development of antibodies against ACE2. [...]

The difference in the percent of subjects with ACE2 antibodies could be due to timing of sample collection relative to the infection, but it could also be due to severity of illness. Wang et al. demonstrated that COVID-19 patients exhibit increases in autoantibodies compared to healthy controls and that patients with more severe disease develop higher levels of autoantibodies.

Assuming the inference above is correct, then the key to avoiding "long COVID" is avoiding severe disease. This argues in favor of vaccination. Furthermore:

Second, there are anecdotal data suggesting that patients experiencing PASC, who become vaccinated with a SARS-CoV-2 vaccine may have improvement. This is also aligned with Jerne’s Network Theory, as the vaccine may induce the immune system to balance the idiotypic and anti-idiotypic antibodies for homeostatic control.

There are ongoing studies on vaccination as treatment for Post-Acute Sequelae of COVID-19 (PASC), with promising results but poor statistical confidence so far. This is also consistent with results from British surveys showing a reduced percentage of PASC in vaccinated individuals. Provided these results bear out, they also point to additional therapies that could block ACE2 inhibition due to this mechanism, for those who are vaccinated but develop PASC anyway.

The bottom line with this study is that we are learning a great deal more about the immune response and how to optimize it against SARS-CoV-2. From the beginning, the difference in outcomes has been baffling, but over time it is becoming clearer why some individuals do much more poorly than others. Taking this new knowledge into consideration, vaccination continues to offer a significant advantage.

[SAN compnerd]

So the Chinese weapon is worse than we thought.

[lp3056]

Published last week in PLOS One, researchers at the University of Arkansas for Medical Science believe they've found a link between "long COVID," or PASC, and a particular antibody. However, this so-called autoantibody develops during natural infection, not following immunization.

....

The bottom line with this study is that we are learning a great deal more about the immune response and how to optimize it against SARS-CoV-2. From the beginning, the difference in outcomes has been baffling, but over time it is becoming clearer why some individuals do much more poorly than others. Taking this new knowledge into consideration, vaccination continues to offer a significant advantage.

I'm curious if the different vaccine types have a effect as well?

[as_rocketman]

I'm curious if the different vaccine types have a effect as well?

It's a good question. I have a completely speculative guess that the more persistent the inoculation, the more likely an anti-idiotypic response becomes. But as all of the various vaccines clear fairly quickly, we may not be able to detect this.

If it does show up, I'm guessing Janssen will have the strongest correlation, as the AAV approach is a bit more persistent than raw mRNA. I'm not aware of any reports of "long vaccine side effects" showing up, so presumably this is a moot point. However, now we have a much better idea of what to look for, and the methods are straightforward.

[theLBC]

even more reason to recommend and use any/all potential prophylaxes like HCQ and Ivermectin that slow down or prevent the virus from replicating out of control in the first place, instead of fooling your body into creating spike proteins that are similar or the same as proteins that are crucial to the replication of the virus.

[tundraboomer]

This argues in favor of vaccination.

Or an effective therapeutic.

[as_rocketman]

even more reason to recommend and use any/all potential prophylaxes like HCQ and Ivermectin that slow down or prevent the virus from replicating out of control in the first place, instead of fooling your body into creating spike proteins that are similar or the same as proteins that are crucial to the replication of the virus.

Emphasis added. Potential prophylaxes? No. A bird in the hand, as they say... All the speculative dosing in the world does not replace proven mitigations.

--

Or an effective therapeutic.

Something like monoclonal antibody therapy, that intervenes before the onset of severe COVID, should also help with this, yes.

[UCT]

This study has nothing to do with ADE. But this vaccinated case might be ADE related. Not enough information to say. https://www.nbcdfw.com/news/coronavi...-time/2727262/

LARPER, how many vaccinated people were part of the study?

[as_rocketman]

This study has nothing to do with ADE. But this vaccinated case might be ADE related. Not enough information to say. https://www.nbcdfw.com/news/coronavi...-time/2727262/

LARPER, how many vaccinated people were part of the study?

This is a specific kind, but nonetheless satisfies the definition of ADE:

ADE has been documented to occur through two distinct mechanisms in viral infections: by enhanced antibody-mediated virus uptake into Fc gamma receptor IIa (FcγRIIa)-expressing phagocytic cells leading to increased viral infection and replication, or by excessive antibody Fc-mediated effector functions or immune complex formation causing enhanced inflammation and immunopathology. Both ADE pathways can occur when non-neutralizing antibodies or antibodies at sub-neutralizing levels bind to viral antigens without blocking or clearing infection.

[...] available data suggest that the most probable ADE mechanism relevant to COVID-19 pathology is the formation of antibody–antigen immune complexes that leads to excessive activation of the immune cascade in lung tissue.

Source

That's exactly what this is: An antibody-antigen immune complex formation (e.g., RBD and a corresponding antibody) that fails to immediately clear the virus (severe COVID), followed by enhanced immunopathology of an autoimmune response. In this case, the autoantibodies perform an immunosuppressive function that prolongs infection. There is nothing about ADE that makes it specific to vaccines.

This is not the first time you've led with name calling despite not knowing what you're talking about. Drop and give me 20.

With respect to the second question, it is a good one. I looked and I downloaded their table; there is no information regarding vaccination status of their sample. They do not appear to have selected for or against it. Nonetheless, the paper illustrates an important mechanism.

[UCT]

This is a specific kind, but nonetheless satisfies the definition of ADE:



Source

That's exactly what this is: An antibody-antigen immune complex formation (e.g., RBD and a corresponding antibody) that fails to immediately clear the virus (severe COVID), followed by enhanced immunopathology of an autoimmune response. In this case, the autoantibodies perform an immunosuppressive function that prolongs infection. There is nothing about ADE that makes it specific to vaccines.

This is not the first time you've led with name calling despite not knowing what you're talking about. Drop and give me 20.

With respect to the second question, it is a good one. I looked and I downloaded their table; there is no information regarding vaccination status of their sample. They do not appear to have selected for or against it. Nonetheless, the paper illustrates an important mechanism.

No. ADE requires an infection after vaccination or a second infection after a prior infection. The second infection is much worse for the vaccinated person or the person with a prior infection than normally seen with the disease.

Your paper discusses an autoimmune disease, which is why most people should not get vaccinated unless they are at high risk. Most autoimmune diseases caused by vaccination don't manifest until 3 or more years after vaccination. Mimicry is well documented between SARS-2 and numerous human antigens. The authors you cite studied one, ACE-2. There is no way to know if ACE-2 antibodies are the cause of Long Covid symptoms or some other antibody created through a mimicry process.

For a discussion on mimicry and SARS-2, see generally https://www.frontiersin.org/articles...617089/full#h5

Papers suggesting that vaccinations might decrease the symptoms of Long Covid (FYI, I haven't read them) are interesting. When you are allergic to something, the shots you receive for allergies are massive doses of the same antigen you are allergic to. The shots exhaust your antibodies to that antigen so you don't get symptoms of allergy. The same might be true in the case of Long Covid and vaccination. If so, once the antibodies wane in 9 months or so after vaccination Long Covid might return.

[as_rocketman]

No. ADE requires an infection after vaccination or a second infection after a prior infection. The second infection is much worse for the vaccinated person or the person with a prior infection than normally seen with the disease.

Nope. There is no requirement for successive infections before it's called ADE. You made that up. ADE can occur on the initial infection, as the paper I linked from Nature and even specific to SARS-CoV-2 makes clear.

What you're describing is another valid ADE scenario, but not the only one.

Your paper discusses an autoimmune disease, which is why most people should not get vaccinated unless they are at high risk.

Obviously, this statement is rubbish. I think you need to apply it less generally -- I believe I know what you meant to say, but clearly, we recommend all kinds of immunization for everyone, despite low risks in the community. Alternately, if you consider everyone at high risk for things like pertussis, then surely SARS-CoV-2 is also a "high risk" pathogen.

The authors you cite studied one, ACE-2. There is no way to know if ACE-2 antibodies are the cause of Long Covid symptoms or some other antibody created through a mimicry process.

I think it is fair to say the connection between ACE2 inhibition and PASC is not proven, though it certainly does result in inflammation consistent with PASC. This is an early study with limited scope, but its conclusions are definite enough for detailed follow-up.

Your paper on mimicry and delayed autoimmune disease is a good read, and the real cause of PASC could be both. They're not exclusive.

Papers suggesting that vaccinations might decrease the symptoms of Long Covid (FYI, I haven't read them) are interesting. When you are allergic to something, the shots you receive for allergies are massive doses of the same antigen you are allergic to. The shots exhaust your antibodies to that antigen so you don't get symptoms of allergy. The same might be true in the case of Long Covid and vaccination. If so, once the antibodies wane in 9 months or so after vaccination Long Covid might return.

Vaccination as therapy has been suggested for quite a while, although with poor statistics as there just aren't that many long haulers available for controlled studies. The original suspicion centered around amplifying an initially weak immune response, i.e., treating vaccination after infection rather like the booster shot being rolled out for immunodeficient folks. This paper is the first I've seen that suggested instead that vaccination would upset the equilibrium between the idiotypic and anti-idiotypic antibody, leading to more efficient clearance and an end to acute infection. That's much more intricate than I expected, but it makes a certain kind of sense.

Time will tell, but I've heard of no speculation at all that PASC will return after a quiet period. Vaccination would be an upset, not an exhaustion. Antibody production is somewhat fungible.