Prospects of a Functional Cure for COVID-19

[RetireBy90]

Covid-19 treatments

WSJ published an opinion piece by Kevin Kimberlin that describes Medical Signaling Cells or MSCs which are found on blood vessels throughout the body. Discovered in 1993 by Arnold Caplan and colleagues. They have been tested at Mount Sinai and other hospitals and showed early signs of eliminating the virus, calming immune overreaction called cytokine storm, and repared damaged lung tissue.

Interesting piece if you can get it behind the WSJ firewall

https://www.wsj.com/articles/the-treatment-that-could-crush-covid-11597360709

Another link if you can't get wsj link - Appears to be same piece.

https://www.regmedfoundation.org/2020/08/14/the-treatment-that-could-crush-covid/

Might be a good thread to post news on developments on treatments

 

[eytonxav]

This does sound promising and could be available soon. It would appear to be a treatment (therapeutic) for someone already infected vs being a vaccine to prevent catching Covid.

 

[sengsational]

I think you mean "Mesenchymal Stem Cells".

We need to do some more digging on these guys, but I watched a few minutes of this video and I think they are talking about the mechanism of action of this approach:

374 views so far, so not mainstream, by any means. But they don't seem to be hyping anything.

These guys are plastic surgeons that have noticed a similarity between severe burn victims with Systemic Inflammatory Response Syndrome (SIRS) and the Covid-19 cytokine storm, and what these MSC's are doing or might do in these two different conditions.

 

[RetireBy90]

Not sure these are the same item. If you read the piece in post 1 they call them “medicinal signaling cells,” or MSCs. I’m not familiar with this or stem cells, but sounds llike 2 different things.

 

[sengsational]

If you Google "medicinal signaling cells,” the results are full of references to mesenchymal stem cells, which suggests that they're the same. But I didn't go any farther than that.

 

[timo2]

Rather than a vaccine, I'm hoping for a treatment for COVID -19 that has similar results to the treatments developed for HIV/AIDS. A treatment that ends up being a functional cure or therapeutic vaccine where the virus is reduced to undetectable and harmless levels in the body permanently, but some residual virus may remain. A treatment may stop the damage to the organs of the body that are a hallmark of COVID-19. A treatment may also help the long-haulers. Especially when I see reports that an vaccine is considered a success even if it is only 50% effective and I see all the money and political interests jockeying for positions in the vaccine market, I think perhaps people have too high of hopes for a vaccine.

I have heard doctors interviewed on TV say that there are groups working on a functional cure or therapeutic vaccine. This is hopeful, especially since some of our top scientists also worked on the HIV/AIDS breakout. I'm happy that their efforts seem to be under the political radar. Which may explain the limited information out there on the web as it relates specifically to work on treatments for COVID-19. But there more information out there on the concept and how it worked for HIV/AIDS.

 

[Sunset]

A treatment for Covid-19 instead of a vaccine would result in much more never ending sales for the medical industry.

I'm hoping for a vaccine, so it can go like Polio.

 

[audreyh1]

Sounds to me like the vaccine developers are well aware that their long term reputations are on the line and concerned about public perception, so they are working hard to pledge to the public about safety. They may resist untoward political pressure because they don’t want a public relations disaster. I’m sure there are also concerns about public acceptance of new vaccines.

I’ve been learning about the vaccines and there are several in Phase 3 or close, so there seem to be several approaches and probably different trade offs. Some may be appropriate for elderly, other for younger folks. I haven’t given up yet. https://www.factcheck.org/2020/09/qa-on-coronavirus-vaccines/

I’m going to listen to what Dr. Hotez has to say about the different vaccines.

 

[samm]

A treatment for Covid-19 instead of a vaccine would result in much more never ending sales for the medical industry.

Exactly!! Sad to say.
My sister in law (PhD, U_Michigan, Ann Arbor) who works in research for one of the "big pharma" said the industry does NOT WANT CURES...but long term treatments to maximize revenues.

She said this as a matter of fact...like I am stupid for not getting "the system"

 

[timo2]

Sounds to me like the vaccine developers are well aware that their long term reputations are on the line and concerned about public perception, so they are working hard to pledge to the public about safety. They may resist untoward political pressure because they don’t want a public relations disaster. I’m sure there are also concerns about public acceptance of new vaccines.

I’ve been learning about the vaccines and there are several in Phase 3 or close, so there seem to be several approaches and probably different trade offs. Some may be appropriate for elderly, other for younger folks. I haven’t given up yet. https://www.factcheck.org/2020/09/qa-on-coronavirus-vaccines/

I’m going to listen to what Dr. Hotez has to say about the different vaccines.

Yes, there have been press releases lately about the pharmaceutical companies pledging not to cut corners. I'll believe it when the kumbaya moment happens.

A vaccine is not going to be a universal remedy like the polio or measles or smallpox vaccines. Only the politicians are giving that false hope, which is why this is disturbing issue for me. A vaccine will not make everything go back to how things were. There are distribution issues to all 7.5 billion people, minus the anti-vaccine folks. Plus as you noted the vaccines may not work for everyone the same. Even with a vaccine, we will need treatments. From what I've read the experts say, the treatments can be moved to market faster. Plus the long-haulers still will need help. Even with a vaccine, there may be a need to continue wearing the dreaded m*sks until almost everyone on earth is immune.

Here is a link to an article on the need for both treatments and vaccines. But this article is sort of glossy and doesn't cover what will be needed for the long-haulers.
https://www.statnews.com/2020/08/05/we-need-a-covid-19-vaccine-but-we-need-new-treatments-too/

That was a good link you gave. Here is one that was embedded in the statnews article link listed above. According to this there are 315 treatments and 210 vaccines being pursued.
"FasterCures, a center of the Milken Institute, is currently tracking the development of treatments and vaccines for COVID-19 (coronavirus). This tracker contains an aggregation of publicly-available information from validated sources."
https://milken-institute-covid-19-tracker.webflow.io/#vaccines_intro

 

[Another Reader]

Yes, there have been press releases lately about the pharmaceutical companies pledging not to cut corners. I'll believe it when the kumbaya moment happens.

A vaccine is not going to be a universal remedy like the polio or measles or smallpox vaccines. Only the politicians are giving that false hope, which is why this is disturbing issue for me. A vaccine will not make everything go back to how things were. There are distribution issues to all 7.5 billion people, minus the anti-vaccine folks. Plus as you noted the vaccines may not work for everyone the same. Even with a vaccine, we will need treatments. From what I've read the experts say, the treatments can be moved to market faster. Plus the long-haulers still will need help. Even with a vaccine, there may be a need to continue wearing the dreaded m*sks until almost everyone on earth is immune.

Here is a link to an article on the need for both treatments and vaccines. But this article is sort of glossy and doesn't cover what will be needed for the long-haulers.
https://www.statnews.com/2020/08/05/we-need-a-covid-19-vaccine-but-we-need-new-treatments-too/

That was a good link you gave. Here is one that was embedded in the statnews article link listed above. According to this there are 315 treatments and 210 vaccines being pursued.
"FasterCures, a center of the Milken Institute, is currently tracking the development of treatments and vaccines for COVID-19 (coronavirus). This tracker contains an aggregation of publicly-available information from validated sources."
https://milken-institute-covid-19-tracker.webflow.io/#vaccines_intro

Yes, we long haulers need treatment. Many of us are just trying to hang on until treatment is available. Sadly, more long haulers are being created with each wave of new cases. I hear indirect reports a lot of younger ones are now showing up in the healthcare systems locally. Being dumped on PCP's that have no care to offer.

There is a lot of discussion about this being a persistent virus that hides out in immune privileged locations. Many long haulers may still have active virus. They could benefit from from convalescent plasma, hyper immune globulin, and monoclonal antibodies. None has been offered so far, although apparently a study of hyper immune globulin to be conducted by Mt. Sinal Hospital and Yale Medicine was at least discussed.

Sadly, I fear this will be like the first couple of years of HIV. Few treatments, lots of deaths. The time frame will be compressed because of the sophisticated research tools, but there will still be a significant lag.

And for those that think hydroxychloroquine is dead as a treatment? Check out clinicaltrials.gov for trials of this drug...

 

[Another Reader]

For a look at how grim things might be for SARS-CoVid-2 survivors, look at what happened to the SARS survivors from 2003. Here is a 2010 update on the Canadian survivors.

https://www.thestar.com/life/health...ivors_struggle_with_symptoms_years_later.html

 

[Fermion]

Exactly!! Sad to say.
My sister in law (PhD, U_Michigan, Ann Arbor) who works in research for one of the "big pharma" said the industry does NOT WANT CURES...but long term treatments to maximize revenues.

She said this as a matter of fact...like I am stupid for not getting "the system"

So this is why Gilead and others spent so much money (over 11 billion for just Gilead) on Hep C cure?

To prove the point, they did see the profit from the cure drop incredibly over a very short period of time (couple of years) and the stock dropped as well.

It would be like if Apple developed a I-phone that updated itself hardware and software so you never needed to buy another phone. How many investors would be piling into Apple then?

 

[Rianne]

For a look at how grim things might be for SARS-CoVid-2 survivors, look at what happened to the SARS survivors from 2003. Here is a 2010 update on the Canadian survivors.

https://www.thestar.com/life/health...ivors_struggle_with_symptoms_years_later.html

We are early in understanding the impact of this virus. I mentioned this in another post, my DC is an administrative nurse at Johns Hopkins. Children are coming in to ER presenting Vasculitis type symptoms. They had Covid with few or no symptoms and were not tested or DX at the time of infection. They are testing positive for antibodies. The inflammation and vascular impacts are frightening. One boy 15 yrs old in critical condition. Heart and organs affected.

 

[Another Reader]

We are early in understanding the impact of this virus. I mentioned this in another post, my DC is an administrative nurse at Johns Hopkins. Children are coming in to ER presenting Vasculitis type symptoms. They had Covid with few or no symptoms and were not tested or DX at the time of infection. They are testing positive for antibodies. The inflammation and vascular impacts are frightening. One boy 15 yrs old in critical condition. Heart and organs affected.

Testing positive for antibodies dies not necessarily mean the virus has been cleared, just that the body is trying to fight it. If this is a persistent virus that hangs out in immune privileged places, it will be very difficult to clear.

I read that health insurance rates next year will be going up by 20 percent on average as insurance companies are seeing the costs of treating COVID skyrocket. With no organized treatment, PCP's and specialists are using a lot of expensive diagnostic resources to figure this out. There are long haulers that have been to the ER 15 times or more.

 

[Chuckanut]

We are early in understanding the impact of this virus. I mentioned this in another post, my DC is an administrative nurse at Johns Hopkins. Children are coming in to ER presenting Vasculitis type symptoms. They had Covid with few or no symptoms and were not tested or DX at the time of infection. They are testing positive for antibodies. The inflammation and vascular impacts are frightening. One boy 15 yrs old in critical condition. Heart and organs affected.

Listen to the last 10-12 minutes of this podcast. It's grim. But, also hopeful. We need to do it right.


https://www.peoplespharmacy.com/articles/show-1226-the-coronavirus-hunter-gives-you-an-update

It’s really too early to determine what all the long-term consequences (called sequelae; you’ll hear us say “sick-KWELL-ee”) of this viral infection might be. There is a chance that some people will suffer for months or potentially even years, because we are already seeing individuals who no longer have the virus but are not yet recovered. Problems with lungs, blood vessels, the heart, the digestive tract and the brain are all showing up.

 

[audreyh1]

I read somewhere recently that patients going through pulmonary rehab were seeing healing in lungs and even other organs.

Here it is Covid-19's 'serious, long-term impact' can improve with time, early evidence suggests

Covid-19 can have lasting impacts on the body, but there is hope that patients can not only recover over time, but can do so more quickly with pulmonary rehabilitation, preliminary research suggests.

..... "The bad news is that people show lung impairment from COVID-19 weeks after discharge; the good news is that the impairment tends to ameliorate over time, which suggests the lungs have a mechanism for repairing themselves," Dr. Sabina Sahanic, a clinical PhD student at the University Clinic in Innsbruck, Austria, who was involved in one of the reports, said in a news release.

https://www.cnn.com/2020/09/06/health/covid-19-long-term-effects-study-wellness/index.html

The article is disturbing in that it talks about how much damage these patients experience. But it also appears there is improvement with rehab.

 

[Another Reader]

In case you missed this one, Andy Slavitt's "In the Bubble" podcast today is about Long Haulers.

https://podcasts.apple.com/us/podca...sodeGuid=e41eb42e-c991-443e-bf52-ac2c013dd8a6

If you are really interested in vaccines and treatments, it looks like anyone can register for this webinar on Thursday.

https://aspeninst.zoom.us/webinar/register/WN_ux3YOAMTT-ec4BR_n7E7eQ

Dr. Krammer's lab isolated the spike protein and distributed it to other researchers and designed the Mt. Sinai antibody test, which detects antibodies to the spike protein, and actually works.

 

[gindie]

I'm following the progress of Dr. Jacob Glanville. He was featured on the Netflix series "Pandemic" for his work on a universal flu vaccine, before COVID-19 was on the scene. Then he switched most of his work to COVID, developing a therapeutic known as "monoclonal antibodies".

They are not a vaccine, rather a treatment for those who get the virus. His company is one of several developing these approaches. Dr. Fauci and the head of the CDC are both optimistic that something like this will work. This approach was highly successful in combating Ebola.

Dr. Glanville is different than the other researchers in that he shares the behind-the-scenes details of his work directly to the public in laymen's terms. His latest update was a couple of weeks ago at

 

[timo2]

Sounds to me like the vaccine developers are well aware that their long term reputations are on the line and concerned about public perception, so they are working hard to pledge to the public about safety. They may resist untoward political pressure because they don’t want a public relations disaster. I’m sure there are also concerns about public acceptance of new vaccines.

I’ve been learning about the vaccines and there are several in Phase 3 or close, so there seem to be several approaches and probably different trade offs. Some may be appropriate for elderly, other for younger folks. I haven’t given up yet. https://www.factcheck.org/2020/09/qa-on-coronavirus-vaccines/

I’m going to listen to what Dr. Hotez has to say about the different vaccines.

From today's LA Times, an article that dovetails with your post. It includes a link to the original statement from the drugmakers:
"The chief executives of nine drugmakers leading the race to produce vaccines against the coronavirus signed a joint pledge Tuesday in an effort to boost public confidence in any vaccines that are ultimately approved by the U.S. Food and Drug Administration or similar agencies around the world.

The companies said they will follow “high ethical standards and sound scientific principles” as they conduct their time-sensitive work against a global pandemic.

“We believe this pledge will help ensure public confidence in the rigorous scientific and regulatory process by which COVID-19 vaccines are evaluated and may ultimately be approved,” the companies said.

Public health officials in the U.S. worry that if many Americans don’t trust the vaccines that become available and decline to get them, it will be harder to reduce the spread of COVID-19.".....

..Specifically, the nine firms pledged to:

• Make the safety of people who receive coronavirus vaccines their “top priority.”

• Conduct clinical trials of their experimental vaccines according to “high scientific and ethical standards.”

• Seek regulatory approval for candidate vaccines only after safety and efficacy have been established through Phase 3 clinical trials.

• Produce a range of vaccines to meet the differing needs of people around the world.

The most interesting part for me, that lines up with this thread is the "Produce a range of vaccines to meet the differing needs of people around the world." That is very interesting and implies coordinated releases.

https://www.latimes.com/science/sto...dEpDHv_sQ2IeNa6I4OSf96zPJtAXaquq5qqtuKopB3iJg

in case the LA times is firewalled, here is the vaccine maker statement http://www.news.sanofi.us/2020-09-08-Biopharma-leaders-unite-to-stand-with-science

 

[daylatedollarshort]

Recent studies show being vitamin D deficient raise risks by 77% - https://www.upi.com/Health_News/202...fection-risk-by-77-study-finds/7001599139929/

And treatment with vitamin D lowered ICU admissions dramatically - https://www.sciencedirect.com/science/article/pii/S0960076020302764

So just not being D deficient and treating people who are deficient would help a lot. I wonder what the risk is for people who aren't deficient in any nutrients would be? We're spending a huge amount of money on shutting down the economy and unemployment when it wouldn't cost trillions of dollars for vitamin D testing and correction. We're ignoring the low hanging fruit.

 

[audreyh1]

What I thought was amazing was that having sufficient vitamin D levels reduced risk of infection dramatically.

We don’t know if generally healthier, wealthier people who have more resources to stay or work at home, not stuck in front line jobs with more exposure, also tend to have higher blood vitamin D levels just like they tend to have better health in general. There could be some confounding factors.

It’s disappointing that the article did not give the Vitamin D blood level considered a deficiency. This seems to differ depending on the health authority, so it would be nice to know what level was used as the cutoff in this study.

OK - I found it in the JAMA paper:

Vitamin D deficiency was defined by the last measurement of 25-hydroxycholecalciferol less than 20 ng/mL or 1,25-dihydroxycholecalciferol less than 18 pg/mL before COVID-19 testing

 

[Freedom56]

AstraZeneca has paused its vaccine trial after safety concerns.

https://www.statnews.com/2020/09/08...d-adverse-reaction-in-participant-in-the-u-k/

https://www.cnbc.com/2020/09/08/ast...coronavirus-vaccine-study-is-put-on-hold.html

 

[explanade]

I'm following the progress of Dr. Jacob Glanville. He was featured on the Netflix series "Pandemic" for his work on a universal flu vaccine, before COVID-19 was on the scene. Then he switched most of his work to COVID, developing a therapeutic known as "monoclonal antibodies".

They are not a vaccine, rather a treatment for those who get the virus. His company is one of several developing these approaches. Dr. Fauci and the head of the CDC are both optimistic that something like this will work. This approach was highly successful in combating Ebola.

I think there was some early optimism for monoclonal antibodies. Regeneron said back in the spring they hoped to have hundreds of thousands of doses of their monoclonal antibody cocktail of two antibodies by end of summer or fall.

Now we hear we should get data by the end of this month.

But I read a Barron's article citing one analyst that Regeneron missed their chance, because the antibody cocktail was being tested both as treatment and prophylactic. If they delivered the cocktail before vaccines, Regeneron could have had huge sales for prophylactic use.

When they do deliver it, it may be a somewhat irrelevant, hard to manufacture and expensive therapeutic.

More promising is EIDD 2801, an antiviral compound discovered at Emory University and being developed by Merck and Ridgeback, a bio startup. It can be taken in pill form, unlike remdesivir (though Gilead is trying to develop a nebulizer form which can be made into an inhaler).

We are suppose to get data on EIDD-2801 this month as well.


More promising I think are nano bodies. These are in animals such as llamas and camels. These are much smaller than human antibodies and may be easier to manufacture than monoclonal antibodies.

Now, UCSF researchers have synthesized nanobodies in the lab and have devised a triple-nanobody formulation which attach to all 3 RBDs of the spike protein, effectively blocking the virus from infecting cells.

This lab-designed nano bodies are very cheap to manufacture and can be delivered by an inhaler, to both treat and protect against infections.

Though engineered entirely in the lab, AeroNabs were inspired by nanobodies, antibody-like immune proteins that naturally occur in llamas, camels and related animals. Since their discovery in a Belgian lab in the late 1980s, the distinctive properties of nanobodies have intrigued scientists worldwide.

“Though they function much like the antibodies found in the human immune system, nanobodies offer a number of unique advantages for effective therapeutics against SARS-CoV-2,” explained co-inventor Aashish Manglik, MD, PhD, an assistant professor of pharmaceutical chemistry who frequently employs nanobodies as a tool in his research on the structure and function of proteins that send and receive signals across the cell’s membrane.

For example, nanobodies are an order of magnitude smaller than human antibodies, which makes them easier to manipulate and modify in the lab. Their small size and relatively simple structure also makes them significantly more stable than the antibodies of other mammals. Plus, unlike human antibodies, nanobodies can be easily and inexpensively mass-produced: scientists insert the genes that contain the molecular blueprints to build nanobodies into E. coli or yeast, and transform these microbes into high-output nanobody factories. The same method has been used safely for decades to mass-produce insulin.

https://www.ucsf.edu/news/2020/08/4...owerful-inhalable-protection-against-covid-19

 

[timo2]

Here is some work towards a potential treatment:
"A druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus from infecting human cells has been discovered by an international team of scientists led by the University of Bristol. The researchers say their findings, published today [21 September] in the journal Science, are a potential 'game changer' in defeating the current pandemic and add that small molecule anti-viral drugs developed to target the pocket they discovered could help eliminate COVID-19.
....
There is reason for hope. In rhinovirus, a virus causing the common cold, a similar pocket was exploited to develop potent small molecules that bound tightly to the pocket distorting the structure of the rhinovirus, stopping its infectivity. These small molecules were successfully used as anti-viral drugs in human trials and show promise for treating rhinovirus clinically. The Bristol team, based on their data, is optimistic that a similar strategy can now be pursued to develop small molecule anti-viral drugs against SARS-CoV-2."


https://www.bristol.ac.uk/news/2020...-2 Spike protein,by the University of Bristol.