Just curious, anyone have a plan, or preps for global pandemic?

[Dean Pomerleau]

This new preprint [1] (popular press article) of an Israeli study seems to show a booster for the Pfizer vaccine may be required at six months. It looked at the viral load (cycle threshold or Ct) of breakthrough infections with Delta that occurred at different times post double vaccination or post a booster shot.

Here is the main graph from the paper:

The tall two bars on the left of the graph show it took many cycles to detect the virus in breakthrough infections that occurred within two months of the second dose of Pfizer meaning the viral load was greatly attenuated by the vaccine (by a factor of 15). But after that the viral load rapidly increased (shorter bars for lower cycle numbers) to the point where after 180 days (six months) it was indistinguishable from unvaccinated people who were infected.

Breakthrough infections after a third dose (booster) of the Pfizer vaccine (rightmost bar in left graph) resulted in a much lower viral load (by a factor of ~4) compared with the unvaccinated.

To generate these graphs, the researchers measured viral load in the first positive test that the infected people in the study received, which may have clouded the results somewhat. E.g. if vaccinated people were more likely to be asymptomatic they may never have even been tested which would underestimate the power of the vaccine to reduce viral load. Or if the vaccine brings down viral load faster than normal, the first test might miss the peak of viral load in vaccinated people, overestimating the power of the vaccine to keep viral load to a minimum.

These results also only measured viral load in the nasal cavity not the lungs or elsewhere in the body where it really counts for disease severity. But the viral load in the nasal cavity is what counts for transmissibility and is also likely to correlate with viral load elsewhere in the body and hence disease severity.

Overall it looks like a booster shot for the Pfizer vaccine may be warranted. The fact that the booster doesn't do as good a job at reducing viral load in breakthrough infections as did the initial two doses seeming concerning. The author's say they don't know how long the restored protection after the booster will last.

They don't mention the troubling possibility that the attenuated ability of the booster to limit viral load from breakthrough infections compared with the initial two shots (i.e. ~4x reduction after booster vs. ~15x reduction after initial doses), might be due to further evolution within the Delta clade making it more virulent. If so, this would seem to be indirect evidence for Todd's hypothesis of vaccine-induced selection pressure for more virulence.

But there is another, perhaps more likely explanation that would also account for the fact that the standard 2 doses of the Pfizer vaccine appears to remain effective at preventing severe disease (even in Israel) after many months despite little reduction in viral load in the nasal cavity soon after a Delta breakthrough infection.

If the protection afforded by the vaccine migrates from circulating antibodies to T-cells and memory B-cells after the first couple months, the body's response to infection may be delayed (relative to soon after vaccination when circulating antibodies are high) in order to give these components of the immune system time to ramp up antibody production to fight the infection. This would allow the level of the virus in the nasal cavity to grow rapidly during the first few days post infection. But once these B-cell-generated antibodies kick in after a few days, they rapidly reduce the viral load before the infection can spread to the lungs or other organs, thereby preventing severe infections.

Note the two explanations aren't mutually exclusive. That is, there may be selection pressure in favor of viral strains that rapidly reproduce in the nasal cavity (like Delta) to avoid and/or overwhelm the early immune system response, particularly in those people who've been vaccinated for a while and therefore have a delayed (but still potent) immune response. This would give the virus time to spread to others as a result of early high viral load in the nasal cavity before the immune system of the vaccinated person has a chance to kick in to fight it.

If this is the case, then a booster shot would be warranted if the goal is to reduce transmission even while the standard 2-dose regime remains effective against hospitalization and death.

As I said previously, let's hope scientists are making progress on alternative vaccines, including one that could be administered nasally that might have a better chance of stopping the virus reproduction early and therefore prevent transmission.

But in the meantime, it seems to me that both the limited ability of the 2-dose vaccine regime to reduce viral load beyond the first two months and the inability of even a booster shot to fully restore the ability of the vaccine to attenuate viral load makes the case that we may want to continue with non-pharmaceutical countermeasures like masks and social distancing if we want to reduce transmissions.

Then again, if vaccines (with or without boosters) continue to be effective at preventing severe disease, it looks like some (many?) vaccinated folks may just say "screw the unvaccinated and immunocompromised, I'm not going back to masks and distancing." Heck the vaccinated folks may not even chose to get a booster if it looks like the protection it provides against high viral load and transmission will likely be short-lived and unnecessary for preventing severe disease.

--Dean

--------

[1] Viral loads of Delta-variant SARS-CoV2 breakthrough infections following vaccination and booster with the BNT162b2 vaccine

doi: https://doi.org/10.1101/2021.08.29.21262798

This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

Abstract

The BNT162b2 vaccine showed high real-life effectiveness both at preventing disease and in reducing viral loads of breakthrough infections, but coincidental with the rise of the Delta-variant SARS-CoV2, these protective effects have been decreasing, prompting a third, booster, vaccine inoculation. Here, analyzing viral loads of over 11,000 infections during the current wave in Israel, we find that even though this wave is dominated by the Delta-variant, breakthrough infections in recently vaccinated patients, still within 2 months post their second vaccine inoculation, do have lower viral loads compared to unvaccinated patients, with the extent of viral load reduction similar to pre-Delta breakthrough observations. Yet, this infectiousness protection starts diminishing for patients two months post vaccination and ultimately vanishes for patients 6 months or longer post vaccination. Encouragingly, we find that this diminishing vaccine effectiveness on breakthrough infection viral loads is restored following the booster vaccine. These results suggest that the vaccine is initially effective in reducing infectiousness of breakthrough infections even with the Delta variant, and that while this protectiveness effect declines with time it can be restored, at least temporarily, with a booster vaccine.

[Todd Allen]

20 hours ago, Dean Pomerleau said:

I'd very much like to hear your thoughts on those crucial issues. Is it the timing issue you are worried about? ie widespread vaccinations will accelerate selection pressure and thereby potentially make more virulent strain dominate more quickly, possibly before scientists have time to develop better vaccines to combat them? 

That was the biggest issue for me in April.  The Marek's vaccines each lasted for years before immune escape developed.  But they were traditional vaccines produced from cultured virus generating broad immune response.  The covid-19 vaccines available in the US target a narrow range of antigens making them more susceptible to immune escape.  I think Read is correct that even without vaccination immune escape would develop as the antigens were all in the spike protein and are key to transmission and thus subject to great selection pressure in the unvaccinated.   But it is widely believed that in a vaccinated population the selection pressure is further refined to the strains that spread best through the vaccinated.  We have witnessed decline in covid-19 vaccine effectiveness in the past few months.  Israel was likely the first most extreme example due to vaccinating early and aggressively with a single vaccine.  They also avoided a massive outbreak prior to vaccination and probably had less natural immunity.  But there is evidence vaccine effectiveness is declining in other heavily vaccinated countries.  Rates of hospitalization and death among the vaccinated in the UK are not far behind Israel:  https://www.gov.uk/government/publications/investigation-of-novel-sars-cov-2-variant-variant-of-concern-20201201  Looking at table 5 of the most recent report #22, recent data for the over 50 years category where most deaths occur shows:
 of 71,107 confirmed covid delta cases 6,724 were unvaccinated
 of 7,154 cases of emergency visits resulting in hospital admission 2,019 were unvaccinated
 of 1,644 deaths 437 were unvaccinated
In the UK vaccines still provide modest protection against hospitalization and death per case of infection but looking at previous reports one can see the trajectory is bad.  I no longer see the risk of additional vaccinations accelerating immune escape as an issue of concern.  The vaccines are becoming so leaky the majority of transmission has been occurring among the vaccinated in Israel and the UK.  If leaky vaccines are driving immune escape the process should continue and probably accelerate without additional vaccinations.

The benefit of vaccination is declining not just by loss of efficacy of preventing hospitalization and death but also because case fatality rates have declined in the unvaccinated.  This combined with the risk of ADE is now my primary reason to not get vaccinated.  ADE arises when non-neutralizing antibodies dominate and interfere with neutralizing antibodies.  These vaccines sidestepped this issue by targeting a limited number of antigens for which primarily neutralizing antibodies were produced.  But we see vaccine induced antibody levels plummet in 6 months.  And the evolving spike protein creates significant risk vaccine induced antibodies will lose sufficient capacity to neutralize: SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Quote

We investigated the role of the B.1.617.2 spike as an escape mechanism by testing 33 spike-specific mAbs with an in-vitro PV neutralization assay using Vero E6 target cells expressing Transmembrane protease serine 2 (TMPRSS2) and the Wuhan-1 D614G SARS-CoV-2 spike or the B.1.617.2 spike (Extended Data Figure 1 and Extended Data Table 2). We found that all three NTD-mAbs (100%) and four out of nine (44%) non-RBM mAbs completely lost neutralizing activity against B.1.617.2. Within the RBM-binding group, 16 out 26 mAbs (61.5%) showed a marked decrease (2-35 fold-change reduction) or complete loss (>40 fold-change reduction) of neutralizing activity to B.1.617.2 (Extended Data Figure 1).

 

There is also the possibility current vaccinations interfere with future vaccines better targeted to the viral strains of the day.  This has been seen with flu vaccines and is hypothesized to be aggravated when the evolutionary distance between a new vaccine and its targeted antigens grows large compared to the distance between the new vaccine and previous vaccines.  Serial Vaccination and the Antigenic Distance Hypothesis: Effects on Influenza Vaccine Effectiveness During A(H3N2) Epidemics in Canada, 2010–2011 to 2014–2015

 

Here is Read's 2015 paper on Marek's: 

Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens

Quote

Vaccination could prompt the evolution of more virulent pathogens in the following way. It is usually assumed that the primary force preventing the evolutionary emergence of more virulent strains is that they kill their hosts and, therefore, truncate their own infectious periods. If so, keeping hosts alive with vaccines that reduce disease but do not prevent infection, replication, and transmission (so-called “imperfect” vaccines) could allow more virulent strains to circulate. Natural selection will even favour their circulation if virulent strains have a higher transmission in the absence of host death or are better able to overcome host immunity. Thus, life-saving vaccines have the potential to increase mean disease virulence of a pathogen population (as assayed in unvaccinated hosts) [2–4].

Considering covid-19 vaccines are losing their capacity to reduce disease and so far the virus has been evolving toward increased infectiousness with no apparent increase in deadliness among the unvaccinated I agree with Read's position that the risk of vaccines driving increased deadliness is no reason to skip vaccination.  But the reasons I have pointed out should weigh into one's personal risk to benefit ratio calculations.  For myself I feel no urgency to act as I don't currently perceive an emergency level of personal threat and I am content to continue waiting and watching to see how this evolves.

Quote

At every point in the 50-year history of vaccination against Marek’s disease, an individual chicken exposed to the virus was healthier if it was vaccinated.

This may be true but it is also true that Marek's disease now flares much more severely in unvaccinated flocks.  If Marek's evolves to make the jump into wild birds it could be devastating.  Likewise imagine a scenario where a covid-19 vaccine produces full protection against disease while still being leaky for infection and transmission.  This could produce positive feedback between vaccination rates and viral deadliness leading to a utopia where all of humanity must be vaccinated and harbors an ever more virulent virus that could devastate wildlife.

Edited September 7, 2021 by Todd Allen

[Sibiriak]

28 minutes ago, Todd Allen said:

The benefit of vaccination is declining ... by loss of efficacy of preventing hospitalization and death

But the efficacy in preventing hospitalization and death is still quite robust.  That's the crucial fact for me.

 

28 minutes ago, Todd Allen said:

This combined with the risk of ADE is now my primary reason to not get vaccinated.

The risk of ADE seems purely speculative at this point.

 

28 minutes ago, Todd Allen said:

I don't currently perceive an emergency level of personal threat and I am content to continue waiting and watching

That makes some sense.  Hopefully  your threat perception is accurate.

Edited September 7, 2021 by Sibiriak

[Mike41]

https://www.sciencedaily.com/releases/2021/08/210804123547.htm
 

if you want an early booster shot right now get a regular flu shot!

[Dean Pomerleau]

16 hours ago, Todd Allen said:

... vaccines still provide modest protection against hospitalization and death per case... 

More than modest I would say. Take a look at this graph from here:

Pretty striking protection against death since July 1st in the US. Admitted that could change with new variants or waning efficacy, but so far vaccines appear to remain very protective against hospitalization and death. 

16 hours ago, Todd Allen said:

...case fatality rates have declined in the unvaccinated. 

The statistic you should really be looking at is the fatality rate (or infection rate) in the unprotected (like yourself) not the unvaccinated. There is an ever-growing population of people like Matt, who are unvaccinated but are protected from infection, hospitalization and death by the immune response triggered by a previous infection. Data out of Israel shows previously infected but unvaccinated folks appear to be at least as well protected as vaccinated folks, perhaps better.

So it seems to me you are at risk of being overconfidence if you are looking at the entire unvaccinated population and thinking a positive trend in case fatality rate (which I'm not sure even exists except for your claim, although it may be true for everyone, not just unvaccinated, as more effective treatments like monoclonal antibodies become more widely available) applies to you as someone who is unvaccinated and without the protection of a previous infection.

--Dean

[Saintor]

It is about time  that we do like in Sweden.  Let herd immunity win and not get insane about it.

https://www.reuters.com/world/europe/sweden-remove-most-remaining-pandemic-restrictions-this-month-2021-09-07/

I am sympathetic to vaccines (and an admirer of Salk in the 50s) but most people give them benefits that they don't have.   They are mostly designed to protect the hosts, do very little for spreading.    Now we see Israel as a top spot for new  infections  - they were the leaders in vaccination.     

https://nationalpost.com/news/world/israels-covid-19-surge-shows-the-world-whats-coming-next

Even Palestine with 6x less vaccination has a better death rate, in an harsher environment.

Aside of vaccines (I got my shots),  for this virus I find most of the other  measures (masks, social distancing BS, confinements ) hysterical, abusive and irrational.  They made a very bad situation much worse.

 

 

Edited September 7, 2021 by Saintor

[Dean Pomerleau]

This article discusses new evidence that getting an mRNA vaccine dose after covid infection triggers the generation of antibodies that are effective against all the circulating variants, something infection alone or vaccine alone doesn't achieve.

It also points to this recent preprint [1] that provides strong support for the idea I discussed a couple posts back - namely that as the level of circulating antibodies wane in the months after receiving the vaccine, other components of the immune system (memory B cells and T cells) are ramping up.

Keep findings include:

• The B-cell derived antibodies in vaccinated people were effective at binding to the key part (the RBD) of the spikes from Alpha, Beta and Delta variants.
• These effective antibodies were higher in vaccinated people than in people who recovered from a mild covid infection.

This supports the explanation I discussed before for why vaccines wane over time in effectiveness against infection but remain effective against hospitalization and death. Namely:

On 9/6/2021 at 4:59 PM, Dean Pomerleau said:

If the protection afforded by the vaccine migrates from circulating antibodies to T-cells and memory B-cells after the first couple months, the body's response to infection may be delayed (relative to soon after vaccination when circulating antibodies are high) in order to give these components of the immune system time to ramp up antibody production to fight the infection. This would allow the level of the virus in the nasal cavity to grow rapidly during the first few days post infection. But once these B-cell-generated antibodies kick in after a few days, they rapidly reduce the viral load before the infection can spread to the lungs or other organs, thereby preventing severe infections.

--Dean

------

[1] mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern

Rishi R. Goel, Mark M. Painter, Sokratis A. Apostolidis, Divij Mathew, Wenzhao Meng, Aaron M. Rosenfeld, Kendall A. Lundgreen, Arnold Reynaldi, David S. Khoury, Ajinkya Pattekar, Sigrid Gouma, Leticia Kuri-Cervantes, Philip Hicks, Sarah Dysinger, Amanda Hicks, Harsh Sharma, Sarah Herring, Scott Korte, Amy E. Baxter, Derek A. Oldridge, Josephine R. Giles, Madison E. Weirick, Christopher M. McAllister, Moses Awofolaju, Nicole Tanenbaum, Elizabeth M. Drapeau, Jeanette Dougherty, Sherea Long, Kurt D’Andrea, Jacob T. Hamilton, Maura McLaughlin, Justine C. Williams, Sharon Adamski, Oliva Kuthuru, The UPenn COVID Processing Unit, Ian Frank, Michael R. Betts, Laura A. Vella, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Scott E. Hensley, Miles P. Davenport, Paul Bates, Eline T. Luning Prak, Allison R. Greenplate, E. John Wherry

doi: https://doi.org/10.1101/2021.08.23.457229

ABSTRACT

SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.

[BrianA]

Idaho activates Crisis Standards of Care in North Idaho due to surge in COVID-19 patients requiring hospitalization

 

https://healthandwelfare.idaho.gov/news/idaho-activates-crisis-standards-care-north-idaho-due-surge-covid-19-patients-requiring

[Gordo]

Dean, regarding mask wearing - I'm open to correction, but my current thinking is that asymptomatic spread has been greatly overblown.  If I am not feeling well, I'll wear a mask or just not go out in public at all.  And of course I'm also vaccinated which lowers my chance of becoming a spreader if I do get infected.  I'm also at lower risk of infection because I work from home and don't have to be in close contact with very many people.  I suppose the peer aspect also plays a role, if everyone else was masking, I might also, if almost no one is masking (which is the case in my area currently) I'm probably not going to be the one person wearing a mask (but I would if I was not feeling well and for some reason was in a public place anyway).  We did the mask thing for over a year, how long will you keep it up?  What if covid is with us forever?  You could of course also apply your line of reasoning to almost any infectious disease, you could have killed people by passing around the flu before covid-19 was a thing, did you always wear a mask in public before covid19?  If not, why not?   Masking was quite popular in some countries even before covid, so there are places where its routine even in "normal" times.  I think masking lowers quality of life, hinders breathing (especially if using a proper mask that actually works), can irritate one's ears, and just not being able to see faces is a bit dehumanizing.  My wife has a student right now who is nearly deaf, and the masking is causing her serious problems (not being able to see lips makes it impossible to understand what someone is saying).  But I do think it would be nice if everyone who had even the slightest symptom of illness would mask up in public, and that should be a permanent thing (I have read that is common curtesy in Japan for example).

[Gordo]

NEW DETAILS EMERGE ABOUT CORONAVIRUS RESEARCH AT CHINESE LAB

More than 900 pages of materials related to US.-funded coronavirus research in China were released following a FOIA lawsuit by The Intercept.

[Dean Pomerleau]

7 hours ago, Gordo said:

You could of course also apply your line of reasoning to almost any infectious disease, you could have killed people by passing around the flu before covid-19 was a thing, did you always wear a mask in public before covid19?  If not, why not?

I stopped wearing a mask for a month or so early in the summer when it looked like the risk serious outcome for myself and other vaccined people from covid was approaching that of the flu. But with the Delta surge I reversed course and started wearing a mask again in indoor public spaces, despite the fact that most people aren't anymore, for example in Lowe's or Aldi, despite the fact that the majority of people in my area aren't anymore. 

If people would at least wear a mask when they are sick, that would be nice. But as you said, peer pressure has a big impact on people's behavior, and if nobody but the sick are wearing a mask, many of the sick will choose not to either for fear of stigma. Plus masks protect the wearer as well. Given how much more transmissible Delta is and how much more quickly it reproduces in the nose, I would not discount the potential for asymptomatic or very mildly symptomatic transmission. 

7 hours ago, Gordo said:

 I think masking lowers quality of life, hinders breathing (especially if using a proper mask that actually works), can irritate one's ears, and just not being able to see faces is a bit dehumanizing. 

If I had to wear a mask all the time (eg for an 8-hour workday) I might see it as a substantial burden. But I consider the modest downside of masking while shopping in stores (really my only public exposure these days) to be a small price to pay for the potential benefits to myself and others while Delta is surging and unvaccinated kids are back in school. I think I would feel even more strongly this way if someone I knew well has recently died from covid despite being vaccinated.

--Dean 

[mccoy]

In Italy everyone still wears a mask in indoor public places, whereas in the outdoors it's not mandatory presently (depending upon the alert degree).

I can wear a surgical mask without much inconvenience, whereas FPP2 and FPP3 tend to be bothersome.

[Dean Pomerleau]

From this article in The Atlantic: What We Actually Know About Waning Immunity.

Some reports from Israel appear to paint a more dire portrait: A few preliminary numbers released by the country’s Ministry of Health suggested that vaccine effectiveness against both infection and symptomatic disease had dipped to about 40 percent. But Çevik, of the University of St. Andrews, told me that these and other data reporting heftier declines are messy and might actually overestimate the problem. Across countries, early vaccine recipients tended to be older, in slightly worse health, and in higher-risk professions than those who got injected later on. That alone could make the protection that they got seem less impressive in comparison. Also, when initial effectiveness numbers were calculated, people were adhering more to physical distancing and masks. Measured these days, amid more lax behavior, risk of infection would rise. And as more of the unvaccinated have been infected, their collective immunity has grown, making them, too, less susceptible to the virus—which could make the effectiveness of vaccines look lower.

... 

When it comes to severe disease and death, though, vaccine effectiveness hasn’t really budged at all: Immunized people seem to be thwarting the worst cases of COVID-19 just as well as they did when the shots debuted, often at rates well into the 90s. That’s fantastic, considering that the FDA’s original benchmark for vaccine success, announced in June 2020, was reducing the risk of disease or serious disease by 50 percent among people who get the shot. So far, there is simply no “evidence of a substantial decline” against the worst outcomes, Saad Omer, an epidemiologist at Yale, told me. 

... 

For the rest of us, though, the perks [of a booster shot] are harder to visualize. In someone with a fully functional immune system whose defenses were already substantially shored up by their first shots, more doses would probably increase antibody production. That, in turn, could further cut down on infection and transmission, Gommerman told me. Very early data hint that this may be happening in Israel, which is already boosting widely. But it’s not clear how long that preventive bump would last. Ellebedy, of Washington University in St. Louis, said boosters would have “real gain” only if they expanded on the body’s capacity to manufacture antibodies long term, instead of just fueling a temporary boom-and-bust. It’s especially unclear whether that would happen with yet another injection of the original vaccine recipe, delivered to the arm—as opposed to, say, a nasal spray with Delta-specific ingredients.

--Dean 

[Dean Pomerleau]

Results from the Together trial, the largest to-date randomized control trial of ivermectin for treatment of covid have been announced (via video - not yet published).

They randomly assigned 1350 people in Brazil across ten clinics who just been diagnosed with Covid to receive either three days treatment of ivermectin or placebo. The outcomes they looked at were ER visits due to worsening symptoms, hospitalizations and mortailty. They found ivermectin provided no benefit relative to placebo, with 86 ER visits/hospitalizations in the ivermectin group vs. 95 in the placebo group, which was not a statistical significant different (CI 0.69 - 1.19). Impact on mortality risk was also non-significant (CI 0.44 - 1.52).

This is the second time the Together trial has tested ivermectin, this time with a higher dose and longer treatment, and again it failed to show any benefit. The researchers report they have dropped the ivermectin protocol from their trial in order to focus on more promising treatments with different repurposed drugs. Hydroxychloroquine and metformin were also found previously to be ineffective by this same group. Below is the slide the researchers shared about the ivermectin results at around 31 minutes of the video.

--Dean

[BrianA]

Attempting to only mask up when you feel sick doesn't work well with this variant in particular. Studies have shown the most contagious period is in the 2 days before you show symptoms (if you get symptoms at all), and that vaccinated individuals have roughly comparable viral load/spreading ability during this initial time period compared to non-vaccinated.

[Ron Put]

Again "the science" was recommending against mask-wearing by healthy people under most circumstances, as it had never been proven to be effective. Then came the political pressure and most Western medical groups caved in, because who wants to be "cancelled" and have their career destroyed by the Left? The studies that were cobbled together by "the scientists" who were paraded on CNN, MSNBC and the pages of The NYT were shoddy, at best, but Covid and the Left have politicised and changed scientific discourse dramatically.

On another note, here is a thoughtful interview with Robert Malone. After the brief defence of his character and career prompted by recent personal attacks by the left, he gives a rather good overview of the current state of vaccines.
 

 

Edited September 8, 2021 by Ron Put

[Dean Pomerleau]

5 minutes ago, Ron Put said:

... as [mask wearing] had never been proven to be effective.

Large Study Confirms Masks Work to Limit COVID-19 Spread

The mask intervention was tested in a randomized control trial in Bangladesh on 350,000 people in many different villages. The intervention resulted in a 28% increase in people wearing masks (13% -> 42%) which in turn resulted in a 10% decrease in confirmed symptomatic cases of covid.

If you naively linearly scaled that result so that it was going from 0% mass usage to 100% mask usage, it would equate to a 36% reduction in symptomatic covid infections.

That is likely a substantial underestimate for reasons given in article, and because the benefits of nearly universal mask usage would almost certainly be super-linear, since near universal masking would greatly increase the fraction of encounters between masked infected people and masked uninfected people, which are the type of encounter where masks are most effective.

--Dean

[Gordo]

3 hours ago, Dean Pomerleau said:

it would equate to a 36%

What's the point though? Do you think having 100% of people masking 100% of the time in public is going to stamp out covid permanently? Doesn't seem likely. A 36% reduction won't matter. I still kind of feel like almost everyone will be exposed eventually, we are just prolonging the inevitable. It's not that different from the last big worldwide flu pandemic (which never really went away). 

[BrianA]

Twitter thread and link to paper from July showing long term kidney damage even in non-hospitalized covid cases:

 

 

[Dean Pomerleau]

7 hours ago, Gordo said:

What's the point though? Do you think having 100% of people masking 100% of the time in public is going to stamp out covid permanently? Doesn't seem likely. A 36% reduction won't matter. I still kind of feel like almost everyone will be exposed eventually, we are just prolonging the inevitable. It's not that different from the last big worldwide flu pandemic (which never really went away). 

Gordo, 

I totally understand feeling covid fatigue at this point in the pandemic, especially after losing a friend to the disease. You may be right and vitually everyone is destined to get covid eventually so why take extra, inconvenient steps like masking to avoid it.

All I can offer is an analog with aging and death. Despite what some folks in the anti-aging community like to believe, we are all going to get old and die eventually. Maybe our grand kids won't, but we will. But that doesn't mean that I stop doing what I can to remain healthy and postpone death, even at some near term cost in convenience and hedonistic enjoyment. 

We all have to decide for ourselves how we want to balance risk vs annoyance. Just like with CR, many will fall off the wagon. And just like with the 1918 flu, a couple years down the road there will be some people who can look back and say I was careful and didn't get covid during its more deadly waves. I'm someone who is willing to endure interventions than many people seem to consider too burdensome at this point In order to increase my chances of being one of them. And if I do end up getting covid, interventions like masking (and obviously vaccination!) should help to minimize its severity and its long-term impact on my health. 

YMMV. 

--Dean 

[Dean Pomerleau]

8 hours ago, Gordo said:

Do you think having 100% of people masking 100% of the time in public is going to stamp out covid permanently? 

No of course not. But returning to widespread masking (on top of vaccines) might help prevent our hospitals from being overwhelmed and having to institute business closures, on-line schooling and lockdowns again. 

--Dean 

[Todd Allen]

An attack on "science" by John Ioannidis.  A bit ranty and light on specifics although when ones house is on fire merely yelling fire is understandable.

https://www.tabletmag.com/sections/science/articles/pandemic-science

[Gordo]

10 hours ago, BrianA said:

Twitter thread and link to paper from July showing long term kidney damage even in non-hospitalized covid cases:

Good to know.  There may also be confounders of note, see:

https://blogs.bcm.edu/2021/03/11/how-does-covid-19-impact-the-kidneys/

Quote

While nephrologists continue to learn about the correlation between COVID-19 and kidneys, preliminary observations show that patients with kidney disease are at higher risk of contracting the virus due to a weakened immune system. 

...Patients with diabetes or hypertension are most at-risk for kidney failure

 

Edited September 9, 2021 by Gordo

[Gordo]

5 hours ago, Dean Pomerleau said:

No of course not. But returning to widespread masking (on top of vaccines) might help prevent our hospitals from being overwhelmed and having to institute business closures, on-line schooling and lockdowns again. 

I definitely get that, if my local hospitals were near capacity or even if case counts in my county were very high, I'd probably be a lot more cautious.  My county by the way has an over 98% vaccination rate (excluding kids under 12).

[Dean Pomerleau]

Here is an useful visualization from Axios illustrating the point that Todd made last week, namely that the virus is continuing to rapidly mutate. It shows the prevalence of different variants in the US over the course of the year:

It shows the Alpha variant being rapidly replaced by Delta in June, and the original Delta strain slowly getting superceded by several different Delta substrains over the past couple months.

--Dean