COVID Treatment Advances

[Chocaholic]

With 200 news stories each day about vaccines, exactly 0 each day regarding treatment advances, it seems a topic worthy of discussion. Posting in OT hoping to avoid nonsense.

So, a few questions...in record time we have highly touted and publicized vaccines available to the general public. Yet when an early infected patient presents at a hospital, they’re told to go home, quarantine and come back once you struggle to breathe. With literally every medical condition, early treatment is the best path to recovery. Why not COVID?

Almost two years into the pandemic, there are no approved and reasonably reliable treatments that can be prescribed and administered at home. There is no media discussion and no messaging from the CDC other than to ignore everything you’ve heard that “may” work. It won’t.

I’m sure there are trials going on but clearly without urgency. Is the presence of these EUA vaccines expected to negate the urgent need for readily available and reliable treatment? We’ve already seen that’s not the case. Yet, here we are.

Let’s try to avoid the conspiracy theories around the vaccine companies, politics, etc. So, what gives? We need reliable and available treatments desperately.

[Sooner or later]

https://pharmaceutical-journal.com/article/feature/everything-you-need-to-know-about-the-covid-19-therapy-trials

Latest:
On 20 July 2021, Japan became the first country to grant full approval for the use of Regeneron’s casirivimab and imdevimab antibody cocktail to treat patients with mild to moderate COVID-19;
Among patients hospitalised with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without invasive mechanical ventilation at day 29 (Caricchio et al, 20 July 2021);
On 19 July 2021, the EMA announced that it had started evaluating an application to extend the use of Kineret (anakinra) to include treatment of coronavirus disease 2019 (COVID-19) in adult patients with pneumonia who are at risk of developing severe respiratory failure;
Among outpatients with SARS-CoV-2 infection, treatment with a single dose of oral azithromycin compared with placebo did not result in a greater likelihood of being free of symptoms at day 14 (Oldenburg et al, 16 July 2021).

Everything you need to know about the COVID-19 therapy trials
There are thousands of clinical trials investigating treatments and preventative measures for COVID-19.

Antivirals:

Remdesivir
Chloroquine/hydroxychloroquine
Amodiaquine
Artesunate
Lopinavir/ritonavir combination
Favipiravir
Ribavirin
EIDD-2801
Niclosamide
Nitazoxanide
Oseltamivir
Ivermectin
AT-527
Immune modulators:

Dexamethasone
Hydrocortisone
Convalescent plasma
Budesonide (inhaled)
AZD7442
Azithromycin
Doxycycline
Interferons
Tocilizumab
Sarilumab
Regdanvimab
Canakinumab
Anakinra
Baricitinib
Ruxolitinib
Tofacitinib
Acalabrutinib
Imatinib
Brensocatib
Ravulizumab
Namilumab
Infliximab
Adalimumab
Otilimab
Medi3506
Monoclonal antibody cocktail
Bamlanivimab (monotherapy)
Etesevimab (monotherapy)
Sotrovimab
Leronlimab
Risankizumab
Lenzilumab
IMU-838
Other or multiple mechanisms:

Colchicine
Dimethyl fumarate
Angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers
Statins
Aspirin
Clopidogrel
Anticoagulants
Bemcentinib
Omeprazole
Famotidine
Zilucoplan
Ascorbic acid/vitamin C
Vitamin D3
Aviptadil
Tradipitant
Nitric oxide
Fluvoxamine
Proxalutamide
Ruconest
TRV027

[Chocaholic]

Yes, I mentioned many trials under way. So, almost two years in, if I test positive for COVID, what can my doctor prescribe that will effectively treat the virus?

I see aspirin on your list.

Statins too.

No comment.

[URY914]

How can you say "clearly without urgency" You have no idea what is being studied around the world. Because the media hasn't covered it means that it's not happening?

Nevertheless I agree with you that we should have seen some sort of earlier treatment but who knows maybe it is just around the corner.

There has been advances in treatment for those that are severely sick and in the hospital that has proved effective.

[Chocaholic]

Clearly without urgency in the context of a global pandemic. I thought that was clear. So, back to my question. After almost two years, what can your doctor prescribe to treat you effectively if you test positive?



Just saw this headline regarding the CDC’s recommendation.

“CDC document warns Delta variant appears to spread as easily as chickenpox and cause more severe infection”

The entire lengthy article talked about mask wearing and vaccinated people still spreading the virus. The Delta variant is a “new war” yet not a single word about treatment. As if it is irrelevant.

[Sooner or later]

it is a ***** to come up with effective treatments.

They are busting their ass. If you go to the link I supplied it gives up to date info on the various treatments that have/are being looked at.

[javadog]

Personally, I’d probably go with ivermectin.

[GH85Carrera]

Most full scientific trials to run to conclusion, be written up in a medical journal and receive full peer review takes many years.

If a trial looks promising, and hundreds of people are dying steps can be skipped and chances taken in the hope that the new treatment works as indicated in early trials.

That is why all the vaccines are considered experimental. Since the vaccines have been used on millions of people and only a small number have had bad reactions, it was a wise choice to vaccinate.

Remember for decades a ulcer was considered a stress issue, and people were told to reduce stress and eat bland foods and take ant acids. Then a doctor found a virus was the real cause. He actually infected himself, and got an ulcer, and took the cure to prove to himself it worked. It was still a slow process to get the medical community to accept that stress was out, and it was just a virus, Helicobacter pylori.

https://en.wikipedia.org/wiki/Timeline_of_peptic_ulcer_disease_and_Helicobacter_ pylori

[stomachmonkey]

Originally Posted by Chocaholic

Yes, I mentioned many trials under way. So, almost two years in, if I test positive for COVID, what can my doctor prescribe that will effectively treat the virus?

I see aspirin on your list.

Statins too.

No comment.

They are for treatment of complications brought on by the Virus.

Until we can actually treat the Virus itself we need to manage the complications.

If you develop pneumonia you treat the pneumonia. What caused it is secondary at that point.

[jyl]

You're asking is there a treatment suitable to give someone who's been diagnosed with Covid but whose symptoms are just starting and mild (not hospitalized, not on supplemental oxygen)?

AFAIK, right now the only pharmaceutical treatment shown to be effective in that situation is Regeneron's antibody cocktail REGN-COV. See summary of phase 3 data https://investor.regeneron.com/news-releases/news-release-details/phase-3-trial-shows-regen-covtm-casirivimab-imdevimab-antibody

"Effective" means that it substantially reduced the risk of hospitalization or death (by 70% or so), not that it is a silver bullet. I don't know of data for REGN-COV in the Delta variant but I think it is likely to retain effectiveness there as well. Lilly's antibody drug was withdrawn because it isn't effective against some variants. New antibody cocktails are being developed.

REGN-COV is currently available under EUA as an infusion. It hasn't been used all that much (I think several million persons in the US have received it so far) because it isn't that practical to administer a 30-60 minute infusion to 66,000 new Covid patients persons per day. There are around 3,600 infusion centers in the US, very roughly 20 chairs/beds per, so do the math on how infusion capacity. It is even more limited because infusion is typically used for cancer patients, who you really don't want exposed to Covid patients. There are home infusion services but there manpower is the capacity limiting factor.

Of course, if you're Donald Trump, Chris Christie, or other VIP you'll get REGN-COV, and if you're assertive and educated patient able to advocate for yourself, you can likely get it, especially if you're at higher risk.

REGN-COV is being developed in a subcutaneous administration form, which could really relieve the capacity limitations. Watch for that.

Other treatments shown effective so far are for severe Covid (hospitalized), they can somewhat reduce your risk of death, reduce your risk of requiring ventilation, and/or shorten your hospitalization, to varying degrees. Remedsivir, toclizumab, and dexamethasone. I think (am betting money on) that lenlizumab will be added to that list. These are not silver bullets, the improvement shown in clinical trials is generally around 20-30%.

Many pharma companies, large and small, are working on treatments, including for oral and nasal (spray) administration. As just one example, from a tiny UK company (and I'm not suggesting this one is or isn't likely to succeed) https://www.synairgen.com/covid-19/

It is frustrating that therapeutic development hasn't advanced nearly as fast as vaccine development. Frustrating, but understandable. Simplistically, the best time to stop the disease is when the virus has just entered the body, and the most highly-developed, flexible and effective disease-fighter is the body's own immune system, so priming the immune system to quickly recognize and attack the virus (vaccine) or supplementing the immune reaction with man-made antibodies (REGN-COV, etc) is the most effective response so far developed. Once the virus has replicated widely and the patient is sick enough to be hospitalized, it is much harder.

It is also frustrating that the extraordinarily effective vaccines developed in record time aren't being used effectively. We're like the Afghan army or something, even given US weapons and money and air support, many of us abandon our weapons and defect and/or join the Taliban.

Anyway, the development effort being directed at this is immense, and I think effective and practical treatments will be developed. Given that a third of Americans would apparently rather get Covid than take the vaccines that most of the world would die to have access to (sick pun there), therapeutics should remain a big market.

[craigster59]

I was talking with someone the other day, we were wondering about the scenario where an unvaxed person shows up with COVID or the Delta variant.

Can you vaccinate them (and would one work better than the others) and they would immediately start producing antibodies to overcome their current infection, or is it too late and "that train has left the station", they are only good for future infections?

[Chocaholic]

Another interesting observation. Early on there was evidence of viability for HCQ and Ivermectin. With astounding speed both were tested, trialed and quickly shut down as being non-viable treatments.

Additionally I’ve read that there were no federally funded projects to pursue readily available drugs that could prove effective as treatment. Only new drug development. Remember also that manufacturers of cheap, readily available drugs (ex: Ivermectin/Merck) have no incentive to promote cheap, low margin drugs when new developments can be immensely profitable.

Whether such matters play a role in the comparatively slow progress is pure speculation. But certainly a point worthy of consideration.

And JYL...your initial question is confirmed. That’s exactly the question. If I test positive and am very early in the infection process, what can my doctor prescribe to prevent it’s unfettered replication and worsening of symptoms? An infusion is not a viable tool for mass application as you described.

[javadog]

If you look at some of those early treatment studies, especially the ones with hydroxychloroquine, They were giving them to really sick people. Surprise, surprise, it wasn’t effective as a treatment. Once you pass a certain point, it’s not what you want to use.

I would be happy with HCQ, or ivermectin, sitting on my shelf, just in case. Both are not impossible to get, nor expensive. You can probably acquire them before getting an infection, if you really want to be able to nip in the bud.

If you want to go to a more traditional route, I’ve heard that the antibody infusions are pretty effective.

[jyl]

Originally Posted by craigster59

I was talking with someone the other day, we were wondering about the scenario where an unvaxed person shows up with COVID or the Delta variant.

Can you vaccinate them (and would one work better than the others) and they would immediately start producing antibodies to overcome their current infection, or is it too late and "that train has left the station", they are only good for future infections?

Train left station. When virus enters, the person's immune system detects it, the innate immune system (first line of defense) responds. The adaptive immune system (second line of defense) begins to produce antibodies and other responses (B, T cells, etc). It takes time for the adaptive immune system to respond and sometimes that delay allows the virus to replicate so much that severe disease results.

The vaccine works by presenting a synthetic version of the virus' spike protein and thus triggering the adaptive immune response now, so that later, when the actual virus enters, the adaptive immune response has already produced the appropriate antibodies and is ready to respond immediately.

Thus it is pointless to vaccinate someone after they are infected. Their immune system has already started to respond to the virus. It isn't going to respond any faster if you now introduce synthetic spike protein. It has plenty of the real thing to deal with. Arguably, distracting it with the synthetic protein could hurt if the ideal antibody for the real virus is a little different from the antibody for the synthetic (variant issue). And if this person's immune system is not able to respond (immunocompromised etc), then giving it more to do isn't going to help.

[jyl]

Originally Posted by Chocaholic

Another interesting observation. Early on there was evidence of viability for HCQ and Ivermectin. With astounding speed both were tested, trialed and quickly shut down as being non-viable treatments.

Additionally I’ve read that there were no federally funded projects to pursue readily available drugs that could prove effective as treatment. Only new drug development. Remember also that manufacturers of cheap, readily available drugs (ex: Ivermectin/Merck) have no incentive to promote cheap, low margin drugs when new developments can be immensely profitable.

Read that where? Somewhere credible? That is untrue AFAIK. The US NIH and other governments around the world are furiously funding work on everything and anything that could possibly be useful.

Pharma companies are as well. Remember that even though a drug may be generic so that you can't get a composition of matter patent, you may be able to patent your particular formulation of the drug or the method of use against SARS-COV-2. E.g. the little UK company I linked to above is developing interferon beta even though it is generic (indeed, naturally occurring). And for a larger pharma company, can you imagine the public relations and political influence benefits of delivering the world from this scourge? Would be worth billions regardless of drug sales.

And JYL...your initial question is confirmed. That’s exactly the question. If I test positive and am very early in the infection process, what can my doctor prescribe to prevent it’s unfettered replication and worsening of symptoms? An infusion is not a viable tool for mass application as you described.

I am hopeful that the subQ version of REGN-COV will succeed, get EUA, and prove widely useful.
Beyond that, I am very optimistic that a ne ffective treament will be
developed. Eventually.

For now, if I get Covid, I will print out everything I can find on REGN-COV, come up with all the reasons why I'm high risk (which I am, to some degree - as are most on PPOT), and force my doctor to get me that infusion.

[ckelly78z]

Most of the patients who end up on ventilators were vitamin D deficient, my wife, and I have been taking a 5000 mg gel cap daily for the past 1.5 years, and haven't been sick at all.

[Arizona_928]

Originally Posted by Chocaholic

Another interesting observation. Early on there was evidence of viability for HCQ and Ivermectin. With astounding speed both were tested, trialed and quickly shut down as being non-viable treatments.

The World Health Organization reiterated on Wednesday that hydroxychloroquine has potential side effects and should be reserved for clinical trials.

LINK

[Arizona_928]

DCGI approves anti-COVID drug developed by DRDO for emergency use. ie 2-deoxy-D-glucose (2-DG)

LINK

[cabmandone]

A couple mentioned here.

Regeneron seeking authorization as a preventative

[tdw28210]

From April of this year.

This seems to be good news, but not for anything new in the world or Rx, likely contributing to it being somewhat overlooked.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088823/

Conclusions:

"Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.
Keywords: ivermectin, COVID-19, infectious disease, pulmonary infection, respiratory failure"