COVID-19 Antibody Discovery Could Explain Long COVID

[SWAlexander]

The finding is Abzymes (catalytic autoantibodies)
UVA Health researchers have discovered a potential explanation for some of the most perplexing mysteries of COVID-19 and long COVID. The surprising findings could lead to new treatments for the difficult acute effects of COVID-19, long COVID and possibly other viruses.

Researchers led by UVA’s Steven L. Zeichner, MD, PhD, found that COVID-19 may prompt some people’s bodies to make antibodies that act like enzymes that the body naturally uses to regulate important functions – blood pressure, for example. Related enzymes also regulate other important body functions, such as blood clotting and inflammation.

Doctors may be able to target these “abzymes” to stop their unwanted effects. If abzymes with rogue activities are also responsible for some of the features of long COVID, doctors could target the abzymes to treat the difficult and sometimes mysterious symptoms of COVID-19 and long COVID at the source, instead of merely treating the downstream symptoms.

“Some patients with COVID-19 have serious symptoms and we have trouble understanding their cause. We also have a poor understanding of the causes of long COVID,” said Zeichner, a pediatric infectious disease expert at UVA Children’s. “Antibodies that act like enzymes are called ‘abzymes.’ Abzymes are not exact copies of enzymes and so they work differently, sometimes in ways that the original enzyme does not. If COVID-19 patients are making abzymes, it is possible that these rogue abzymes could harm many different aspects of physiology. If this turns out to be true, then developing treatments to deplete or block the rogue abzymes could be the most effective way to treat the complications of COVID-19.”


Understanding COVID-19 Abzymes

SARS-CoV-2, the virus that causes COVID, has protein on its surface called the Spike protein. When the virus begins to infect a cell, the Spike protein binds a protein called Angiotensin Converting Enzyme 2, or ACE2, on the cell’s surface. ACE2’s normal function in the body is to help regulate blood pressure; it cuts a protein called angiotensin II to make a derivative protein called angiotensin 1-7. Angiotensin II constricts blood vessels, raising blood pressure, while angiotensin 1-7 relaxes blood vessels, lowering blood pressure.

Zeichner and his team thought that some patients might make antibodies against the Spike protein that looked enough like ACE2 so that the antibodies also had enzymatic activity like ACE2, and that is exactly what they found.
continue reading: https://newsroom.uvahealth.com/2024/03/26/covid-19-antibody-discovery-could-explain-long-covid/

I found this explanation:
Abzymes (catalytic autoantibodies) belong to an absolutely new group of physiologically active substances with dual characteristics: they represent a pool of canonical autoantibodies and possess catalytic activity. Among them, proteolytic and DNA-hydrolyzing autoantibodies are of special value.

 

[Forummember9922]

How to restore ACE2 and stop such an attack on it?

 

[Empi]

How to restore ACE2 and stop such an attack on it?

If this pans out, probably something like the CAR-T therapy that’s being trialed with success in Lupus. This is really interesting and checks a lot of boxes in terms of being explanatory. I’m really curious what those here who are skilled at picking apart papers like this have to say.

 

[SWAlexander]

I’m really curious what those here who are skilled at picking apart papers like this have to say.

Here is a part of my "investigation" about Abzymes:

https://swaresearch.blogspot.com/2024/03/function-of-abzymes-summary.html

​

 

[Treeman]

Interestingly, this research also focuses on catalytic autoantibodies. It's from Stanford and has a credit for Ron Davies at OMF.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765373/

Abstract

Here we report preliminary data demonstrating that some patients with myalgic encephalomyelitis/chronic fatiguesyndrome (ME/CFS) may have catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP). We propose that these MBP-degradative antibodies are important to the pathophysiology of ME/CFS, particularly in the occurrence of white matter disease/demyelination. This is supported by magnetic resonance imagining studies that show these findings in patients with ME/CFS and could explain symptoms of nerve pain and muscle weakness. In this work, we performed a series of experiments on patient plasma samples where we isolated and characterized substrate-specific antibodies that digest MBP. We also tested glatiramer acetate (copaxone), an FDA approved immunomodulator to treat multiple sclerosis, and found that it inhibits ME/CFS antibody digestion of MBP. Furthermore, we found that aprotinin, which is a specific serine protease inhibitor, specifically prevents breakdown of MBP while the other classes of protease inhibitors had no effect. This coincides with the published literature describing catalytic antibodies as having serine protease-like activity. Postpandemic research has also provided several reports of demyelination in COVID-19. Because COVID-19 has been described as a trigger for ME/CFS, demyelination could play a bigger role in patient symptoms for those recently diagnosed with ME/CFS. Therefore, by studying proteolytic antibodies in ME/CFS, their target substrates, and inhibitors, a new mechanism of action could lead to better treatment and a possible treatment

 

[Empi]

Interestingly, this research also focuses on catalytic autoantibodies. It's from Stanford and has a credit for Ron Davies at OMF.

Great find! I forgot about that study and didn't make the connection. I don't have a science background, so I don't have a deep understanding of the science, however, catalytic antibodies seem really intriguing for a few reasons. First, if I understand correctly, a disease caused by catalytic antibodies would be autoimmune-ish in the sense that it's initiated by the creation of antibodies, but it would not be a traditional autoimmune disease in that antibodies are not directly attacking self. Instead, the antibodies are potentially interfering with bodily processes in unintended ways by functioning as an enzyme.

When I think about Long Covid and/or ME/CFS, I tend to think of things we know to be true, which must be explained in order for a possible cause to be correct. Some of these things are fairly objective, while some are better characterized as good hunches with anecdotal evidence. For instance, we know that both LC and ME/CFS affect women more often than men and in a ratio similar to autoimmune diseases. Second, we know that Rituximab produced some intriguing results for a few individuals, but ultimately failed in clinical trials. Third, and this is more of a guess or inference, is that LC and ME/CFS is probably caused by a mechanism or process that is unknown or not well understood. Otherwise, the disease would probably have been solved. Finally, we know that both LC and ME/CFS are odd in that they are devastating in terms of symptoms, but produce limited physical evidence and are mostly not progressive in their impact. To me, this suggests the body is doing something intentional and maintaining a form of homeostasis, albeit an alternative abnormal homeostasis.

Synthesizing the above, LC and ME/CFS seem like autoimmune diseases in many ways. However, no one has ever found good evidence of an autoimmune process actually occurring. Catalytic antibodies are interesting to me because they provide an explanation for the things that suggest an autoimmune diseases (sex ratios, etc.), while also perhaps explaining why nothing ever turns up when researchers look for evidence of a traditional style autoimmune disease with tissue damage like MS or RA. One could imagine a scenario where catalytic antibodies interact as enzymes in unintended ways and then the body reacts by undertaking a series of compensatory measures to deal with the impact leading to LC or ME/CFS. Finally, I would imagine this fits the mold of things that are unexpected, not well understood, and easily overlooked by researchers. As an additional upside, given the recent breakthroughs with CART-T therapy in autoimmune diseases like Lupus, if this proved to be true it seems like something that would be treatable in the near term. I know these kinds of things are all moonshots in terms of turning out to be correct, but I like this one. .

 

[Wishful]

I still think that ME involves a feedback loop that has shifted to a positive value, locking us into that state. Catalytic antibodies sound like something that could cause a positive feedback loop.

 

[Wishful]

To me, this suggests the body is doing something intentional and maintaining a form of homeostasis, albeit an alternative an abnormal homeostasis.

Yes, I've had many treatments that worked for a few doses, but then stopped working and never worked again, so something is adjusting to the corrective factor to maintain the abnormal state. Homeostasis for the wrong value.

 

[SWAlexander]

Finally, I would imagine this fits the mold of things that are unexpected, not well understood, and easily overlooked by researchers.

I agree. How many research papers mentioned Abzymes before?

 

[Wishful]

How many research papers mentioned Abzymes before?

Wiki says: "To date abzymes display only weak, modest catalytic activity and have not proved to be of any practical use." I'm not sure whether that's referring to artificial abzymes. It mentions their role in autoimmune diseases, but not to how much of a role they play.

 

[SWAlexander]

not to how much of a role they play.

It is explained in the article: "these rogue abzymes could harm many different aspects of physiology."
Wiki is not updated on abzymes.

 

[SWAlexander]

Not only in COVID-19 but also ME/CFS has catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP).

Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome​

Here we report preliminary data demonstrating that some patients with myalgic encephalomyelitis/chronic fatiguesyndrome (ME/CFS) may have catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP). We propose that these MBP-degradative antibodies are important to the pathophysiology of ME/CFS, particularly in the occurrence of white matter disease/demyelination. This is supported by magnetic resonance imagining studies that show these findings in patients with ME/CFS and could explain symptoms of nerve pain and muscle weakness. In this work, we performed a series of experiments on patient plasma samples where we isolated and characterized substrate-specific antibodies that digest MBP. We also tested glatiramer acetate (copaxone), an FDA approved immunomodulator to treat multiple sclerosis, and found that it inhibits ME/CFS antibody digestion of MBP. Furthermore, we found that aprotinin, which is a specific serine protease inhibitor, specifically prevents breakdown of MBP while the other classes of protease inhibitors had no effect. This coincides with the published literature describing catalytic antibodies as having serine protease-like activity. Postpandemic research has also provided several reports of demyelination in COVID-19. Because COVID-19 has been described as a trigger for ME/CFS, demyelination could play a bigger role in patient symptoms for those recently diagnosed with ME/CFS. Therefore, by studying proteolytic antibodies in ME/CFS, their target substrates, and inhibitors, a new mechanism of action could lead to better treatment and a possible cure for the disease.

https://pubs.acs.org/doi/10.1021/acs.biochem.3c00433

 

[Wishful]

Postpandemic research has also provided several reports of demyelination in COVID-19.

"Several reports"? Out of however many millions of victims worldwide, there are only several reports of demyelination? To me that doesn't imply a correlation. Those cases might have had demyelination before getting covid. I haven't read any report that found demyelination in a large percentage of ME victims.

How quickly can demyelination be reversed? I switched from full ME to full non-ME over the span of minutes (and back again over a similar span), so if demyelination and remyelination takes longer than that, I think that it isn't responsible for ME's symptoms.