COVID-19 antivirals and vaccines (Megathread)

[CharonY]

26 minutes ago, Kartazion said:

This means that covid-19 can make a viral rebound and be reactivated in the case of a person who is already a carrier. 
The vaccine won't provide a solution if the virus is hiding. The vaccine will only be effective if the person has never had the virus, right?

No, if one is infected but e.g. with such a low amount that the body did not build up memory, a vaccine that triggers a stronger response can be beneficial. However, a person that has been exposed to sufficient viruses and/or vaccine would mount a faster and stronger response once the virus pops up again and thereby have a higher likelihood to clear the virus before it actually manages to go into hiding. 

[Kartazion]

5 hours ago, CharonY said:

However, a person that has been exposed to sufficient viruses and/or vaccine would mount a faster and stronger response once the virus pops up again and thereby have a higher likelihood to clear the virus before it actually manages to go into hiding. 

That hidden viruses of the immunity could constitute a viral reservoir, and the immune defense no longer reach viruses.
This viral reactivation is a possibility still under investigation.

[hypervalent_iodine]

There was a paper circulating a little while ago that caught my attention, published in Nature. 

https://www.nature.com/articles/s41586-020-2223-y

To be honest, I am pretty baffled that it was published in Nature. The top leads identified in their screening assay are known as pan-assay interference compounds (PAINs). IOW, they are nuisance compounds and generally not something you would pursue in a drug design campaign. In fact, the seminal paper that discusses PAINs is a Nature paper (https://www.nature.com/news/chemistry-chemical-con-artists-foil-drug-discovery-1.15991), which makes this even more confusing. I can't imagine anyone with a med chem background would have reviewed this, as the red flags should have been very obvious. In any med chem journal, this paper would have been rejected since you have to screen for PAINs as part of their submission guidelines. I'm worried that this signals a general lowering of the bar when it comes to these sorts of publications, which will only make things more difficult in the long run. Derek Lowe has written some good blog posts on the matter:

https://blogs.sciencemag.org/pipeline/archives/2020/04/10/more-on-screening-for-coronavirus-therapies

[CharonY]

It does look like that they may not have found the right reviewers. Often reviews are long and iterative in nature and I don't think they are good for these fast turnaround papers where we have to assume a lower certainty.

[BabcockHall]

https://www.statnews.com/2020/04/29/gilead-says-critical-study-of-covid-19-drug-shows-patients-are-responding-to-treatment/

Patients taking remdesivir recovered more quickly than those taking a placebo.  Business Insider and CNN have stories.

[taeto]

19 hours ago, BabcockHall said:

https://www.statnews.com/2020/04/29/gilead-says-critical-study-of-covid-19-drug-shows-patients-are-responding-to-treatment/

Patients taking remdesivir recovered more quickly than those taking a placebo.  Business Insider and CNN have stories.

It makes sense, because remdesivir has been useful against other coronaviruses, SARS so far as I recall, or was it Ebola. Also because the molecule is similar to adenosine and seems able to trick a viral RNA polymerase to try to build it into new RNA strings where adenosine would have belonged, and thus blocking the further production of the viral RNA.

On the other hand, the link states that "Gilead says", and Gilead is a (the?) manufacturer of remdesivir in the US. The available information about the study says that the decrease in lethality among test patients treated with remdesivir was not statistically significant (the shorter recovery times presumably were?)  compared to the patients treated with placebo. And an earlier study of the same drug did not produce any determination. So maybe more tests are needed.

[CharonY]

It has been employed against different viral diseases, incl. SARS, MERS Ebola and a few others. Don't recall respective efficacy, though.

You are also correct that recovery time was the major effect.

[Danijel Gorupec]

If this was already discussed on SFN, please direct me...

Here in eastern europe, there is some speculation that the reason why eastern europe seems less affected by covid-19 (in comparison to the western europe) could be due to previous vaccination against tuberculosis (the BCG vaccine). This seems far fetched to me, but what is your opinion?

[Strange]

8 minutes ago, Danijel Gorupec said:

If this was already discussed on SFN, please direct me...

Here in eastern europe, there is some speculation that the reason why eastern europe seems less affected by covid-19 (in comparison to the western europe) could be due to previous vaccination against tuberculosis (the BCG vaccine). This seems far fetched to me, but what is your opinion?

Is there any evidence that BCG vaccination was more common in Eastern European countries? It was still routine in the UK until very recently, as far as I know.

Even if it is not routine now, it certainly was in the past and so we would expect to see older people less likely to have serious Covid-19 infections, but that is actually the opposite of what we see.

 

Form the WHO:

Quote

There is no evidence that the Bacille Calmette-Guérin vaccine (BCG) protects people against infection with COVID-19 virus. Two clinical trials addressing this question are underway, and WHO will evaluate the evidence when it is available. In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19. WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis.

https://www.who.int/news-room/commentaries/detail/bacille-calmette-guérin-(bcg)-vaccination-and-covid-19

Edited May 10, 2020 by Strange

[Danijel Gorupec]

2 minutes ago, Strange said:

Is there any evidence that BCG vaccination was more common in Eastern European countries? It was still routine in the UK until very recently, as far as I know.

This is what proponents of this idea are pointing out - allegedly, the BCG vaccination is still obligatory in eastern Europe for all children, while is not obligatory in western europe (Portugal being an exception). I didn't check these claims... If UK still has a large portion of population BCG vaccinated, as you suggest, then the idea just falls apart.

[CharonY]

I suspect an easier explanation is a mix of volume of travel from infected areas and potentially incomplete testing. In Russia the number of detected cases are rising rapidly.

[Alex_Krycek]

 

[CharonY]

It should be noted that the drug is a steroid, which are used to manage inflammation and are not antivirals.

[MonDie]

On 4/16/2020 at 8:22 PM, hypervalent_iodine said:

There was a paper circulating a little while ago that caught my attention, published in Nature. 

https://www.nature.com/articles/s41586-020-2223-y

To be honest, I am pretty baffled that it was published in Nature. The top leads identified in their screening assay are known as pan-assay interference compounds (PAINs). IOW, they are nuisance compounds and generally not something you would pursue in a drug design campaign. In fact, the seminal paper that discusses PAINs is a Nature paper (https://www.nature.com/news/chemistry-chemical-con-artists-foil-drug-discovery-1.15991), which makes this even more confusing. I can't imagine anyone with a med chem background would have reviewed this, as the red flags should have been very obvious. In any med chem journal, this paper would have been rejected since you have to screen for PAINs as part of their submission guidelines. I'm worried that this signals a general lowering of the bar when it comes to these sorts of publications, which will only make things more difficult in the long run. Derek Lowe has written some good blog posts on the matter:

https://blogs.sciencemag.org/pipeline/archives/2020/04/10/more-on-screening-for-coronavirus-therapies

Duck, duck, duck, duck, homodimer!!!!

---

 How many months until the vaccine can be approved for widespread use, again?  We might already be immune by that time if they don't disseminate this information carefully.

[CharonY]

24 minutes ago, MonDie said:

Duck, duck, duck, duck, homodimer!!!!

 

---

 How many months until the vaccine can be approved for widespread use, again?  We might already be immune by that time if they don't disseminate this information carefully.

It would fall until the emergency approval pipeline. Herd immunity would take at least another year according to projections, assuming there are no further restrictions.

[stangerzv]

Accumulating evidence suggests anti-TNF therapy needs to be given trial priority in COVID-19 treatment https://www.thelancet.com/.../PIIS2665-9913(20.../fulltext

An inflammatory cytokine signature predicts COVID-19 severity and survival..We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. https://www.nature.com/articles/s41591-020-1051-9

Patent, papaya leaf extract as tnf-alpha inhibitor https://patents.google.com/patent/US20140065251

[Alex_Krycek]

Some interesting research on Ivermectin was released in India back in May.  This is very much a taboo subject in the media, so this paper was met with little fanfare or publicity.  I think it's important to look at all options in the fight against the pandemic, especially for countries with low vaccine rates, and especially due to the ever present threat of breakthrough infections.

"Conclusion and relevance Two-doses of oral ivermectin (300 μg/kg given 72 hours apart) as chemoprophylaxis among HCWs reduces the risk of COVID-19 infection by 83% in the following month. Safe, effective, and low-cost chemoprophylaxis have relevance in the containment of pandemic alongside vaccine."  

Source:  https://assets.researchsquare.com/files/rs-208785/v1/d6ff79a3-d354-4aba-a6b0-4bc123bbd225.pdf?c=1613410891

Video breakdown:  https://www.youtube.com/watch?v=XYv30g7TKVM

 

[Bufofrog]

Instead of taking a drug based on a single study, I would think a better option is to get a vaccine that has been fully approved by the FDA.  Seems a no brainer to me.

That reminds me, it is time to worm my horses...

[Alex_Krycek]

51 minutes ago, Bufofrog said:

Instead of taking a drug based on a single study, I would think a better option is to get a vaccine that has been fully approved by the FDA. 

Currently there is only one vaccine that is FDA approved:  Pfizer.  This vaccine is experiencing serious supply issues at the moment.  

51 minutes ago, Bufofrog said:

Seems a no brainer to me.

Probably because you're fortunate enough to live in a developed country where vaccines are easily accessible.  Is it ethical to deny countries like India from accessing alternative treatments that might save lives?

51 minutes ago, Bufofrog said:

That reminds me, it is time to worm my horses...

Perhaps you should read this study when you finish.

[Bufofrog]

1 hour ago, Alex_Krycek said:

Currently there is only one vaccine that is FDA approved:  Pfizer.  This vaccine is experiencing serious supply issues at the moment.

The other vaccines have been administered to many millions and been shown to be safe and effective, while ivermectin has only one outlier study that showed it helped.

1 hour ago, Alex_Krycek said:

Probably because you're fortunate enough to live in a developed country where vaccines are easily accessible.  Is it ethical to deny countries like India from accessing alternative treatments that might save lives?

It is unethical to give a drug that has not been shown to have any positive effects except in one of the many studies underway.

1 hour ago, Alex_Krycek said:

Perhaps you should read this study when you finish.

Perhaps you should read some of the literature about this study in other publications, like this Nature article.

Nature

[Alex_Krycek]

2 hours ago, Bufofrog said:

The other vaccines have been administered to many millions and been shown to be safe and effective, while ivermectin has only one outlier study that showed it helped.

Vaccines are partially effective at preventing Covid, although data from Israel has suggested they are not as effective as once believed.  These are the current vaccine numbers from India (total population 1,392,700,000).

Participants

• 509,799,626 people with at least one dose administered of Covaxin or Oxford–AstraZeneca vaccine or Sputnik V
• 153,237,708 people have been fully vaccinated with both doses of Covaxin or Oxford–AstraZeneca vaccine or Sputnik V

Outcome

• 37% of the Indian population has received at least one dose.
• 11% of the Indian population has received both doses

Not so great, considering the battle with Delta they are currently involved in.  They should, and are, employ every treatment regimen at their disposal, in addition to vaccines.

2 hours ago, Bufofrog said:

It is unethical to give a drug that has not been shown to have any positive effects except in one of the many studies underway.

These doctors and their patients don't have time to wait around for those in developed countries to deem it justifiable for them to use a treatment like Ivermectin.  If physicians see it working on the front lines - they should use it. 

2 hours ago, Bufofrog said:

Perhaps you should read some of the literature about this study in other publications, like this Nature article.

Nature

"Carlos Chaccour, a global-health researcher at the Barcelona Institute for Global Health in Spain, says it has been difficult to conduct rigorous studies on ivermectin. That’s partly because funders and academics in wealthy countries haven’t supported them, and, he suspects, have often dismissed trials of ivermectin because most of them have been done in lower-income countries. Furthermore, says Rodrigo Zoni, a cardiologist at the Corrientes Cardiology Institute in Argentina, it is difficult to recruit participants because many people — particularly in Latin America — are already taking the widely available drug in an attempt to prevent COVID-19."

“I think it is our duty to exhaust all potential benefits,” says Chaccour, especially given that most countries still do not have widespread access to vaccines. “Ultimately if you do a trial and it fails, fine, but at least we tried.”

-------------------

Most relevant section of the article.  

Edited September 2, 2021 by Alex_Krycek

[TheVat]

Like Bufo, I think it would be good to see some solid peer-reviewed trials that make it past a preprint server.  Otherwise, this sounds a lot like the hydrochloroquine  mass psychosis all over again.  Given the reports coming mainly from southern US states of people taking ivermectin in its veterinary dosage (i.e. horse body mass preparations) and getting quite sick (some have shed the linings of their intestines, which comes out as a sort of rope-like extrusion - aren't you glad to have that detail?), I hope that the hysteria can subside and see if any meaningful facts emerge. 

If vaccines are in short supply many places, that's not a logical argument for taking snake oil.  There is never a "front line" justification for an off-label use of a pharmaceutical when any positive effects (beyond placebo) are unproven.  (if you're just looking for a placebo, try dropping some TicTacs in a pill bottle)  Also, as was the case with 'quine, sometimes the on-label uses are of vital importance and a rush on supplies can deprive others in great medical need, e.g. people suffering from tropical parasites, people who really need their horses to make a living, et al. 

[CharonY]

9 hours ago, Alex_Krycek said:

This is very much a taboo subject in the media

This is what most of the conspiracy bullshitters are stating. The reality is that it is only an issue because for some reasons certain folks run off to dose themselves with horse dewormer rather than using a vaccine that has gone through trials and has been shown to be safe and effective with currently a sample size going in the billion of dosages. Hardly any other medication has that much data available.

With regard to treatment, to date even approved medication like remdesivir have only shown moderate effectiveness in actual controlled trials. Likewise, there were some promising results in early (pre-trial) experiments for ivermectin, but the biggest controlled trial (part of the together trial) did not found a positive effect as outlined in an symposium by the PI of the trial (fluvoxamine seemed more promising, though). 

Trials for treatment options are still ongoing, though so far no magic bullet has been found. The mentioned remdesivir, as well as monoclonal antibodies, high titer convalescent plasma, dexmethasone are currently being used and have generally shown some improvement, though certainly not in all patients. However especially steroids like dexmethasone were likely effective in preventing death in critically ill patients. But obviously that is only useful (as it suppresses inflammation) after things go bad already.

Fundamentally, there is nothing even approaching the effectiveness of vaccines in preventing harmful effects, so it is just madness that folks with access to it prefer to use something that does not show benefits in controlled trials.

I wonder what could motivate to use these drugs vs another, well researched one. Well, not really wonder, more like despair.

In cases where vaccines are not available the solution should not be peddling ineffective measure. Rather we really need to get our act together and get vaccines to everyone on the planet.

 

[John Cuthber]

2 minutes ago, CharonY said:

 

In cases where vaccines are not available the solution should not be peddling ineffective measure. Rather we really need to get our act together and get vaccines to everyone on the planet.

 

Just a quick note for the selfish idiots out there who don't think we should pay to vaccinate people in other countries.
Where do you think the new variants will come from?

[CharonY]

Just now, John Cuthber said:

Just a quick note for the selfish idiots out there who don't think we should pay to vaccinate people in other countries.
Where do you think the new variants will come from?

Always somewhere "Far Away" and it will never impact us. Obviously all diseases come from "exotic" places  where it is not as clean as "here".

I occurred to me that I did not comment on the posted study per se, but as it is reported it has some flaws/issues.

An overall issue is that it is not a placebo controlled study, it is more set up like a retrospective one. While it is not an issue for a small experimental study, it is important to note that the outcome is not in any way comparable to a controlled trial.

A bigger issue that it does not report how they created the study cohort. It seems that folks just decided to take the drug. That has the issue of self selection. I.e. folks taking the drug may also take additional measures to protect themselves. I also cannot see the study group composition (i.e. whether it is built similarly to the control group). So it is not clear to me if both cohorts had equivalent baseline risks. The fact that they found a higher risk for women, indicates some gender bias in the data set- large analyses indicate a similar prevalence for both genders, though severity seemed more common in men.

At best that type of data would indicate that the drug might be suitable for a clinical trial. But, as mentioned, it actually has been and the results were disappointing. This study does nothing to change that outlook.