COVID-19 antivirals and vaccines (Megathread)

[TheVat]

This explores the possibility of viral transport with PM 2.5 particles... 

https://www.nature.com/articles/s41598-021-81935-9

 The rapid spread of the SARS-CoV-2 in the COVID-19 pandemic had raised questions on the route of transmission of this disease. Initial understanding was that transmission originated from respiratory droplets from an infected host to a susceptible host. However, indirect contact transmission of viable virus by fomites and through aerosols has also been suggested. Herein, we report the involvement of fine indoor air particulates with a diameter of ≤ 2.5 µm (PM_2.5) as the virus’s transport agent. PM_2.5 was collected over four weeks during 48-h measurement intervals in four separate hospital wards containing different infected clusters in a teaching hospital in Kuala Lumpur, Malaysia. Our results indicated the highest SARS-CoV-2 RNA on PM_2.5 in the ward with number of occupants. We suggest a link between the virus-laden PM_2.5 and the ward’s design. Patients’ symptoms and numbers influence the number of airborne SARS-CoV-2 RNA with PM_2.5 in an enclosed environment.

 

(I realize the topic may be meandering a little here,  so am open to moving this elsewhere if that works better) 

[Alex_Krycek]

23 hours ago, CharonY said:

Excellent, so I suppose you have dispensed with the notion that somehow there is a cabal restricting ivermectin research, considering that there are sufficiently around to actually try to make a meta-analysis? 

The media in the US is corporate in nature, driven by profit and special interests.  Would anyone have a problem criticizing the media's deceptiveness regarding the wars in Afghanistan or Iraq?  Probably not.  We all recognize the influence that the military industrial complex and defense contractors have on Washington legislators and the corporate media.  It would no doubt be much more acceptable to you to criticize the media if we were discussing those topics, but if one implies that there is some selective messaging going on with respect to Covid, then suddenly criticizing the media is off limits.  Why can we criticize the media in some areas but not others?   I find this inconsistent.

The Pharma lobby is one of the most powerful in the US.  Of course it is plausible that the corporate media would engage in some selective messaging to turn people away from possible cheap alternatives to Covid, as they turned people towards the idea of WMDs in Iraq, or away from the Public Option (it would run insurance companies out of business, right?), and as the media seeks to shape the narrative around a myriad of other issues (universal healthcare, UBI, certain political ideas that fall outside of the status quo, etc).  It's "manufactured consent", as Noam Chomsky puts it. 

The narrow dialogue and fixation on classifying Ivermectin as only a horse dewormer is reflective of this.  The corporate media rarely mentions that Ivermectin is a safe drug that has been used worldwide for decades, nor will they mention the study that I had to proactively search out to begin to understand the full picture.  Instead, the media hypes up the cases of people who misuse the drug, which is a small minority.  Omit any news about Ivermectin to the contrary, and voila - manufactured consent.  It's selective and self serving messaging, with an obvious objective of tarring as fringe elements those who might want to discuss Ivermectin. This in turn gives license to those who blithely follow this narrative to ridicule those who they perceive as ignorant and uninformed.  In the context of what they have been led to believe, this self righteous condescension is logical, but they're missing the bigger picture.

23 hours ago, CharonY said:

If you look at the paper you linked in detail, you will note that especially for prophylaxis they had 3 trials and highlighted that it only has low-certainty evidence of reduction. Even worse, one of the tree trials used for the evaluation was recently withdrawn (at least temporarily). So as a whole there is not a much to shake that particular conclusion.

However, even if we ignore these issues for now, as I mentioned earlier, the data (in part due to the quality of data) suggests at best that a bigger controlled trial is needed to figure out effects rather than jumping the fence and ingesting it because of some positive outcomes.

These are the sections from the study that I found most relevant:

1.  Ivermectin is a well-known medicine that is approved as an antiparasitic by the World Health Organization and the US Food and Drug Administration. It is widely used in low- and middle-income countries (LMICs) to treat worm infections. 2,3 Also used for the treatment of scabies and lice, it is one of the World Health Organization’s Essential Medicines.4  With total doses of ivermectin distributed apparently equaling one-third of the present world population,5  ivermectin at the usual doses (0.2–0.4 mg/kg) is considered extremely safe for use in humans. 6,7 In addition to its antiparasitic activity, it has been noted to have antiviral and anti-inflammatory properties, leading to an increasing list of therapeutic indications.8

2.  A review by the Front Line COVID-19 Critical Care Alliance summarized findings from 27 studies on the effects of ivermectin for the prevention and treatment of COVID-19 infection, concluding that ivermectin “demonstrates a strong signal of therapeutic efficacy” against COVID-19. 9 Another recent review found that ivermectin reduced deaths by 75%. 10

3.  Ivermectin has exhibited antiviral activity against a wide range of RNA and some DNA viruses, for example, Zika, dengue, yellow fever, and others. 13 Caly et al 14 demonstrated specific action against SARSCoV-2 in vitro with a suggested host-directed mechanism of action being the blocking of the nuclear import of viral proteins 14,15 that suppress normal immune responses.

4.  Developing new medications can take years; therefore, identifying existing drugs that can be repurposed against COVID-19 that already have an established safety profile through decades of use could play a critical role in suppressing or even ending the SARS-CoV2 pandemic. Using repurposed medications may be especially important because it could take months, possibly years, for much of the world’s population to get vaccinated, particularly among LMIC populations.

5.  All-cause mortality:  Meta-analysis of 15 trials, assessing 2438 participants, found that ivermectin reduced the risk of death by an average of 62% (95% CI 27%–81%) compared with no ivermectin treatment [average RR (aRR) 0.38, 95% 0.19 to 0.73; I 2 5 49%]; risk of death 2.3% versus 7.8% among hospitalized patients in this analysis, respectively (SoF Table 2 and Figure 3).

6.  The effect on reducing deaths was consistent across mild to moderate and severe disease subgroups.

7.  The cumulative z-curve in Figure 8 crossed the trial sequential monitoring boundaries after reaching the required IS, implying that there is firm evidence for a beneficial effect of ivermectin use over no ivermectin use in mainly hospitalized participants with mild to moderate COVID-19 infection.

8.  The findings indicate with moderate certainty that ivermectin treatment in COVID-19 provides a significant survival benefit.

9.  In addition to the evidence from systematic reviews, the findings of several controlled observational studies are consistent with existing evidence and suggest improved outcomes with ivermectin treatment.55,57,59  Similarly, with respect to ivermectin prophylaxis of frontline workers and those at risk, controlled observational studies from Bangladesh and Argentina (the latter which involved 1195 health care workers) have shown apparent reductions in COVID-19 transmission with ivermectin prophylaxis, including in some reports total protection (zero infections) where infection rates in the control group exceeded 50%. 122,

10.  There is also evidence emerging from countries where ivermectin has been implemented. For example, Peru had a very high death toll from COVID-19 early on in the pandemic. 128 Based on observational evidence, the Peruvian government approved ivermectin for use against COVID-19 in May 2020. 128 After implementation, death rates in 8 states were reduced between 64% and 91% over a two-month period. 128 Another analysis of Peruvian data from 24 states with early ivermectin deployment has reported a drop in excess deaths of 59% at 30+ days and of 75% at 45+ days. 129

11.  Certain South American countries, Indian states, and, more recently, Slovakia and other countries in Europe have implemented its use for COVID-19. 129,131,132,133,134

12.  Given the evidence of efficacy, safety, low cost, and current death rates, ivermectin is likely to have an impact on health and economic outcomes of the pandemic across many countries. Ivermectin is not a new and experimental drug with an unknown safety profile. It is a WHO “Essential Medicine” already used in several different indications, in colossal cumulative volumes. Corticosteroids have become an accepted standard of care in COVID-19, based on a single RCT of dexamethasone. 1 If a single RCT is sufficient for the adoption of dexamethasone, then a fortiori the evidence of 2 dozen RCTs supports the adoption of ivermectin.

13.  Ivermectin is likely to be an equitable, acceptable, and feasible global intervention against COVID-19. Health professionals should strongly consider its use, in both treatment and prophylaxis.

Edited September 4, 2021 by Alex_Krycek

[CharonY]

So now you are shifting away from the prophylaxis  argument and focusing on treatment? That was not the original  argument and obviously  folks are constantly trying to repurchase drugs. Which again runs counter to your narrative. Folks are getting treatment, but obviously after they are sick.

You on the other seem to promote... something. Potentially Self medication for unknown reasons. Now tell me is ivermectin more efficient for treatment than, say remdesivir? Or steroids? I mean the big medical cabal seem to promote  those? Why again are so invested in drugs that are still pending big trials over those that have data? Do you think less evidence is better because somehow pharma is less involved in that?

Sorry  you reasoning seems to me backwards from what it should be.

[Alex_Krycek]

Here's an example of some recent misinformation about Ivermectin in the media.

Rolling Stone, CNN, The Guardian, Fox News, and several other media outlets ran a story about an Oklahoma ER at the NHS Sequoyah hospital.  The source was Dr. Jason McElyea, supposedly an ER doctor at the facility.  Mr. McElyea's statements and portrayal of the situation were refuted by the hospital on their website.  

Here's the headlines that The Guardian and Rolling Stone went with:

 

It turns out that Dr. Jason McElyea hasn't worked at NHS Sequoyah in months, and the hospital issued a formal correction on their website, to counter the false headlines:

 

Sources:  

https://nhssequoyah.com/

https://www.theguardian.com/world/2021/sep/04/oklahoma-doctor-ivermectin-covid-coronavirus

https://www.rollingstone.com/politics/politics-news/gunshot-victims-horse-dewormer-ivermectin-oklahoma-hospitals-covid-1220608/

[CharonY]

Ok so now the argument is that some media outlets have not been fact checking and therefore we should take medication before they go through large trials and getting reviewed?

Look, if you move the goalposts further I am going to need a better telescope.

Edit, also it seems that the articles now include the comment from the NHS, so basically quoting each of the folks involved, which seems to conform to usual standards. Does it mean I should take half the dose? Or do I need to mix it with another experimental drug until the internet hypes up something else (i really hope it coffee).

Edit 2, just to be as sure: don't self medicate with drugs. Ask a MD not the internet. The internet is dumb.

 

[Alex_Krycek]

20 minutes ago, CharonY said:

Ok so now the argument is that some media outlets have not been fact checking and therefore we should take medication before they go through large trials and getting reviewed?

Just pointing out that there's more noise than signal these days, and supposedly reputable outlets aren't immune from the fray.  It's easy to get caught up in the tribalism and name calling.  

20 minutes ago, CharonY said:

Edit, also it seems that the articles now include the comment from the NHS, so basically quoting each of the folks involved, which seems to conform to usual standards.

If they're presented with information that refutes the veracity of the story, they should retract the story, not leave it up as a clickbait headline.  You can't have an entire article portraying the situation in a particular light, based on facts that are then completely undermined with an update appended at the end of the article.  Disingenuous. 

I wrote to The Guardian this morning to request a retraction.  As a paid subscriber I expect better of them.  

10 hours ago, CharonY said:

So now you are shifting away from the prophylaxis  argument and focusing on treatment? 

I'm interested in any information about the efficacy of Ivermectin, for treatment of prophylaxis.  

10 hours ago, CharonY said:

You on the other seem to promote... something. Potentially Self medication for unknown reasons. Now tell me is ivermectin more efficient for treatment than, say remdesivir?

I doubt it, but not many people have access to remdesivir, or the other treatments currently available or in the pipeline.  If people who need a treatment option now can use Ivermectin safely and effectively, why not?  All reasonable options should be on the table.

 

Edited September 5, 2021 by Alex_Krycek

[John Cuthber]

Well, while we are talking about anecdotes, perhaps this one answers the question of  "why not take it?".

 

[swansont]

On 4/13/2020 at 6:24 PM, Casio said:

 

 Ivermectin

Lab tests performed by Australian researchers showed that this anti-parasitic drug stopped the coronavirus growing in cell cultures within 48 hours. This widely available drug has already been shown to be effective against other viruses including HIV, dengue, flu and Zika. 

Ivermectin is already approved by drug regulators and is widely available although it would have to be trialled in patients before becoming an accepted therapy.  

https://www.scholarsresearchlibrary.com/articles/effects-of-ivermectin-therapy-on-the-sperm-functions-of-nigerian-onchocerciasis-patients.pdf

a recent report showed that 85% of all male patients treated in a particular centre with ivermectin in the recent past who went to the laboratory for routine tests were discovered to have developed various forms, grades and degrees of sperm dysfunctions including, low sperm counts, poor sperm morphologies (two heads, Tiny heads Double tails absence of tail’s, Albino sperm calls), azoospermia and poor sperm motility

[CharonY]

!

Moderator Note

Merged topics of treatments into megathread.

 

 

A couple of other recent treatment news:

As mentioned earlier, the TOGETHER trial (which focusses on repurposing of drugs) found evidence for the use of fluvoxamine to reduce the need for emergency room observation (https://www.medrxiv.org/content/10.1101/2021.08.19.21262323v1).

Also as mentioned, Ivermectin was showed no effects, which was communicated in a recent presentation https://trialsitenews.com/mcmaster-together-trial-ivermectin-a-no-show-while-fluvoxamine-shows-some-promise/.

Another trial involving anti-coagulants indicates improved outcomes in moderate severe cases, but little benefit if patients were already critically ill. https://www.nejm.org/doi/10.1056/NEJMoa2105911

Ronapreve has been approved by UK regulators (it is already authorized for emergency use in many countries). The monoclonal antibody cocktail has shown some prophylactic properties in a few phase 3 trials and might also be useful for individuals with compromised immune systems.

 

As a side note, I think this thread documents how difficult it is to translate initial positive findings into actual clinical usefulness. I could write whole articles (in fact, I have) regarding such issues, but looking back, the first post showed potential benefits of hydroxychloroquine and we all know what the trials eventually said. That is why initial positive results of any medical intervention should lead into trials, and not into a call for self-medication.

[CharonY]

An interim report of a phase III trial by Merck indicates that their candidate (Molnupiravir) which seems to be effective in reducing hospitalization and death in mild to moderate COVID-19 cases .

https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/

 

[CharonY]

A report has been finally fully reviewed and has been published indicating high protection after 6 months for hospitalization for the Pfizer vaccine. However, protection against infection drops about by half. I.e. breakthrough infections become more common. Which in turn is especially bad news for still unvaccinated folks as well for efforts to actually curb the viral spread.

https://doi.org/10.1016/S0140-6736(21)02183-8

 

[iNow]

The mental health benefits of vaccines:

We estimate that COVID-19 vaccination reduces anxiety and depression symptoms by nearly 30%. Nearly all the benefits are private benefits, and we find little evidence of spillover effects, that is, increases in community vaccination rates are not associated with improved anxiety or depression symptoms among the unvaccinated. We find that COVID-19 vaccination is associated with larger reductions in anxiety or depression symptoms among individuals with lower education levels, who rent their housing, who are not able to telework, and who have children in their household. The economic benefit of reductions in anxiety and depression are approximately $350 billion. Our results highlight an important, but understudied, secondary benefit of COVID-19 vaccinations.

Source

[CharonY]

The previously referenced TOGETHER study has now also published the results of their ivermectin trial. It was a double-blind, randomized, placebo controlled study with 1,358 participants. Not surprisingly at this point no benefits for ivermectin intervention where demonstrated.

DOI: 10.1056/NEJMoa2115869

Quote

CONCLUSIONS
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424. opens in new tab.)

 

[studiot]

8 hours ago, CharonY said:

The previously referenced TOGETHER study has now also published the results of their ivermectin trial. It was a double-blind, randomized, placebo controlled study with 1,358 participants. Not surprisingly at this point no benefits for ivermectin intervention where demonstrated.

DOI: 10.1056/NEJMoa2115869

 

 

Thanks.

However there is more encouraging news in 'the Prescriber' Magazine (UK).