[barmar]

pilowsky, on 2022-February-22, 06:19, said:

The current coronavirus has settled in nicely and is now as endemic as the influenza virus which has been around for >100 years.

Is it endemic already?

From https://www.marketwa...ors-11645716595

Quote

Moderna said Thursday it expects COVID-19 to become endemic in 2023, meaning it will be another seasonal disease that can be managed with vaccines and treatments.
...
On a call with analysts, Moderna Chief Medical Officer Dr. Paul Burton said the company “firmly” believes that a fourth dose, or a second booster, will be necessary, likely by fall of 2022.

[pilowsky]

barmar, on 2022-February-25, 15:09, said:

Is it endemic already?

From https://www.marketwa...ors-11645716595

It is the virus, sars-cov-2, not the disease COVID-19 that is endemic. Diseases don't become endemic - only infectious agents.
The meaning of endemic is that it is endo- like endocrine, endogenous and endometriosis: it simply means "within".
"-emic" as in pandemic, endemic etc is something related to a single group.
[Edit many use epidemic to describe a surge in an existing non-infectious problem. It does get a bit overused though.]

This does not mean that it cannot be eradicated eventually but that's another problem.

In medicine it also refers to things that are caused by specific physically identifiable particles that have a capacity to reproduce within some kind of host.
In this way tetanus cannot be called an epidemic or even endemic because although Clostridium tetani is found in the ground that you walk on, it isn't transmissible by simple human to human contact.

Coronaviruses are here to stay. The subtype sars-cov-2 virus might mutate (for better or for worse) just like influenza, but it now has an animal population that it doesn't harm that we are in contact with all the time where it can mutate and remerge from at any time.

In fact, I haven't heard of an animal that it doesn't affect.
I think that this is because the binding receptor 'ACE2' is so old evolutionarily that it is present throughout the animal kingdom and throughout the body.

Sars-cov-2 is now endemic. It has a highly mobile collection of hosts - bats, deer, children where it does (relatively) little harm and where it can mutate and occasionally pop-up with new more vicious variant - just like influenza (WHO- "Globally, the World Health Organization (WHO) estimates that the flu kills 290,000 to 650,000 people per year.").

In my mind it became endemic when omicron emerged.
At that point it became "tolerable" - unlike smallpox, leprosy and polio which humans would still like to eliminate.
Other agents that cause a massive burden of disease worldwide seem to be of less interest presumably because they tend to cause few problems for wealthy westerners unless they are making nature documentaries.

There are other biological mechanisms that infectious agents use to mutate and transmit that are not seen in coronaviruses but these differences do not seem to be an issue for coronaviruses maintaining themselves in human accessible reservoirs.
BTW, coronaviruses were around causing disease in humans for a very long time.
Here's one from 1999.
And in 1973.

COVID-19 can also be considered a virus of our time.
It causes most of its unpleasant effects in people that are either older than 65 (something that was much less common in the 1950's - not that long ago).
And in people that have reduced respiratory capacity because of obesity (along with a smaller bunch of other disorders - emphysema, smoking, cystic fibrosis).
This combination of differentially harming people that are overweight/ older than 65/ are smokers is reflected in the populations where it is most damaging.

The meaning of endemic is fairly clear it means that something is no longer just passing through the population and will burnout and not be a problem - that would be an epidemic.

Our ability to combat any disease is markedly hampered by our (I mean societal) disdain for training people in high-level thinking (PhD and up).
Research funding is now at a very low ebb.
It's much easier to dislike Mexicans, Canadians and New Zealanders than it is to spend two decades of your life training and learning how to solve really difficult problems.
COVID-19 is a disorder that weaves together all the threads in the water cooler: education, climate change, political philosophy and more.

Speaking of endemic problems, the current crisis also highlights the epidemic of scam journals and conferences.
I wish some of the cyber-security experts out there like Jim Browning would go after these people - they probably operate from the same call centres as the Amazon scammers.

PS
This is also why religion although it is transmissible and "of the population" is not endemic in the USA, or elsewhere - except metaphorically.

[Gerardo]

pilowsky, on 2022-February-25, 16:29, said:

In my mind it became endemic when omicron emerged.
At that point it became "tolerable"

Could this be because, while (still) highly transmissible, omicron (reportedly(?))
does not attack the lungs like other variants?

[pilowsky]

Gerardo, on 2022-February-28, 05:34, said:

Could this be because, while (still) highly transmissible, omicron (reportedly(?))
does not attack the lungs like other variants?

The evidence is very clear that omicron will bind to the ACE2 receptor wherever it is present in the respiratory tract.
It's early days yet and the reason that omicron is less of a problem is unclear.
The cells lining the nose and throat are similar in their expression of ACE2 to the expression in the cells in the lung - it's one continuous layer throughout the airway.

I suspect the largest reason omicron is causing less severe illness and death is because so many people are vaccinated.
In countries where vaccination is patchy omicron is still causing problems.
So-called "natural immunity" and "healthy living" is orders of magnitude less helpful than a three doses of vaccine.

Just to speculate, if the omicron variant changed in such a way that it binds much more avidly to the receptor one could imagine that when you inhale a dose of virus much more of it will be trapped by receptors in the upper airway and this means less gets to the lungs.
This would change the way the disease affects the host.

If you are familiar with chromatography you could imagine that viral particles that bind more strongly would get stuck at the top: the principle is the same.
I'm only suggesting this by analogy to the size-exclusion principle that our airways uses to prevent particulate matter from getting into the lungs.
I have no actual evidence.

Another possibility is that something else in the virus particle that determines how easily it latches onto the cellular machinery to make more virus mutated so that if it gets in it is less damaging.
This seems less likely but again, no evidence.

Training people and funding research so that when pandemics roll around is vital but not a high priority for government.
The success rate for grant-funding is very low compared to the excellent proposals.
Now we have the additional problem that politicians think they know what should be funded.
They create "priority areas" and funding is not decided solely on the basis of excellence.

How many Hollywood films do we see where a post-doc fights off aliens and saves the world.

US movie/video expenditure in 2019 was ~65+ billion. It has been since at least 2007.
The NIH spends about 42 billion annually on medical research.

There are other sources of medical research funding but the entertainment industry also includes sport and television.

Every hospital bed seems to have a television, but I don't know if it helps as much as a ventilator.

[y66]

Matt Yglesias said:

I want to flag this thread!

https://twitter.com/...465032547061767

Do not entirely agree with the counterarguments offered but it correctly identifies a SIGNIFICANT factual error in my newsletter.

Dr. Angela Rasmussen said:

@mattyglesias isn’t convinced by the recent preprints (one of which I co-authored) placing the zoonotic origin of SARS-CoV-2 at the Huanan Seafood Market.

And after reading https://www.slowbori...ew-lab-leak?s=w it’s clear that he fundamentally misunderstands them.

[barmar]

pilowsky, on 2022-February-25, 16:29, said:

It is the virus, sars-cov-2, not the disease COVID-19 that is endemic. Diseases don't become endemic - only infectious agents.
The meaning of endemic is that it is endo- like endocrine, endogenous and endometriosis: it simply means "within".
"-emic" as in pandemic, endemic etc is something related to a single group.

That's not what the dictionary says:

Quote

(of a disease) regularly occurring within an area or community.

Compare with epidemic, pandemic
‘areas where malaria is endemic’

But that doesn't seem to be how it's used when saying that the disease/virus will transition from pandemic to endemic. I will presumably still be worldwide, but it will become tolerable like the flu and common cold. As I understand it, modern influenza is a variant of the virus that caused the 1918 pandemic, but regular vaccinations keep it under control.

[pilowsky]

barmar, on 2022-March-11, 03:31, said:

That's not what the dictionary says:


But that doesn't seem to be how it's used when saying that the disease/virus will transition from pandemic to endemic. I will presumably still be worldwide, but it will become tolerable like the flu and common cold. As I understand it, modern influenza is a variant of the virus that caused the 1918 pandemic, but regular vaccinations keep it under control.

It's a fair point - I'll cop to that.
In any event, I think we can say that this diseases caused by coronaviruses are now endemic in the human population and will continue to provide new challenges and mutations in the years to come.

Yes, influenza viruses are the same type of virus as the devastating of 1918.
This virus has been around for centuries and occasionally mutates to a more virulent strain.
It doesn't help that there are so many more humans around and that they are much older and insist on travelling around so much when phone calls and zoom/skype are readily available, but I suppose I used to be one of them.

Hopefully the RNA vaccine approach will make it more likely that we can have polyvalent vaccines in the future that allow a single shot that targets multiple viruses (as discussed in detail with some nice diagrams here).

[Cyberyeti]

https://www.cam.ac.u...avirus-vaccines

My understanding when this was explained on the radio was they were targeting bits of the virus that were less likely to mutate to try to make a vaccine that would work against future variants.

[pilowsky]

Cyberyeti, on 2022-March-11, 05:52, said:

https://www.cam.ac.u...avirus-vaccines

My understanding when this was explained on the radio was they were targeting bits of the virus that were less likely to mutate to try to make a vaccine that would work against future variants.

I think that's another issue.
Both ideas are possible.
I'm not a virologist but it would obviously be a good thing if they could find an antigen on the virus that was static and could not change without losing virulence.
I do have experience in making antibodies. It's very hard.
There are so many problems here.
1) there might be a protein (called the antigen - antigens can have multiple epitopes which are the individual sites antibodies bind to) that is unique and doesn't change but is not on the outside of the virus.
The protein must be exposed to the host to be an 'epitope' if it isn't it's called a 'cryptotope' (or cryptope) this means that antibodies made against it can't see it in the virus and therefore don't work. This is a really common problem when making antibodies.
2) some proteins are incredibly hard to make antibodies to - some are impossible - don't get me started.
3) even if you find a protein that is a good candidate it has to be really really antigenic to be useful for immunising a whole population because it needs to make >99.99% of subjects immune to be effective. Most of the time when making antibodies in the lab. a 2/3 success rate is acceptable. This will not cut it in immunisation programs.
4) Not all antibodies are the same. You have to have an antigen that provokes a really good response resulting in neutralising antibodies in nearly everyone.

I can see why they went for the spike protein. It sits on the outside and looks like the bristles of a brush. Clearly the most likely target.

Another approach is to make a drug that blocks the enzyme that the virus uses to turn the cellular machinery into a virus factory - like molnuprivar which blocks the RNA dependent RNA polymerase (RdRp). Of course this is not good as a prophylactic and can't replace vaccination.

[thepossum]

Cyberyeti, on 2022-March-11, 05:52, said:

https://www.cam.ac.u...avirus-vaccines

My understanding when this was explained on the radio was they were targeting bits of the virus that were less likely to mutate to try to make a vaccine that would work against future variants.

Which to anyone in any discipline would appear eminently sensible. If any Jo Public had to choose to between a general or overly specific vaccine. Not too general etc

I realise also I have a tendency to oversimplify. You should see my approach to modeling sometimes. When I found that the RAT could diagnose all forms of SARS with reasonable accuracy I was curious too. Maybe people are concerned about knocking out beneficial variants. Or maybe some other reason that I don't understand. But I know nothing of the practicalities or detailed technical issues involved

Can I ask a question of those who do know any of this stuff.

From my part-wikipedia level understanding of the immune system doesn't it have a fairly non-specific, complex, allow for error kind-of approach at targetting different parts of invading viruses or other unwanted invaders

[pilowsky]

From a recent report in the New England Journal of Medicine - a generally reputable source.
Published 16 March 2022
This brief letter to the Journal appears to suggest that a fourth dose is extremely safe and causes a marginal improvement in antibody titres.
It is worth noting that the subjects were health care workers (likely to be younger).
A marginal benefit in young people may (or may not) translate into a larger benefit in older people with a disease that causes more problems in an older age group.

Quote

Our data provide evidence that a fourth dose of mRNA vaccine is immunogenic, safe, and somewhat efficacious (primarily against symptomatic disease). A comparison of the initial response to the fourth dose with the peak response to a third dose did not show substantial differences in humoral response or in levels of omicron-specific neutralizing antibodies. Along with previous data showing the superiority of a third dose to a second dose,4 our results suggest that maximal immunogenicity of mRNA vaccines is achieved after three doses and that antibody levels can be restored by a fourth dose. Furthermore, we observed low vaccine efficacy against infections in health care workers, as well as relatively high viral loads suggesting that those who were infected were infectious. Thus, a fourth vaccination of healthy young health care workers may have only marginal benefits. Older and vulnerable populations were not assessed.

[cherdano]

I think this study should be seen in the context that protection vs hospitalisation from 3 doses wanes significantly within 3-4 months. The immunogenicity data basically ensures that this will be restored - we just don't know for how long. If you are eligible for a 4th dose in your country I would certainly take it.

[hrothgar]

In a development that should surprise no one, the ACBL Nationals in Reno look to have lead to a whole bunch of infections...

[Cyberyeti]

cherdano, on 2022-March-23, 14:51, said:

I think this study should be seen in the context that protection vs hospitalisation from 3 doses wanes significantly within 3-4 months. The immunogenicity data basically ensures that this will be restored - we just don't know for how long. If you are eligible for a 4th dose in your country I would certainly take it.

I seem to remember that the opinion was that 2 doses and having then had the virus was better protection than 3 doses. My father, sister and b-i-l are now in the situation of 3 doses then the virus (sis/father not terrible, b-i-l has been quite unwell for a while but is now recovering without hospitalisation), wonder how long their protection will last.

[y66]

From Biden Administration Plans to Offer Second Booster Shots to Those 50 and Up at NYT:

Quote

WASHINGTON — The Biden administration is planning to give Americans age 50 or older the option of a second booster of the Pfizer-BioNTech or Moderna coronavirus vaccine without recommending outright that they get one, according to several people familiar with the plan.

Major uncertainties have complicated the decision, including how long the protection from a second booster would last, how to explain the plan to the public and even whether the overall goal is to shield Americans from severe disease or from less serious infections as well, since they could lead to long Covid.

Much depends on when the next wave of Covid infections will hit, and how hard. Should the nation be hit by a virulent surge in the next few months, offering a second booster now for older Americans could arguably save thousands of lives and prevent tens of thousands of hospitalizations.

But if no major wave hits until the fall, extra shots now could turn out to be a questionable intervention that wastes vaccine doses, deepens vaccination fatigue and sows doubt about the government’s strategy. The highly contagious Omicron subvariant BA.2 is helping to drive another surge of coronavirus cases in Europe and is responsible for about a third of new cases in the United States, but health officials have said they do not anticipate a major surge caused by the subvariant.

Federal health officials have hotly debated the way forward, with some strongly in favor of a second booster now and others skeptical. But they have apparently coalesced around a plan to give everyone age 50 and up the option of an additional shot, in case infections surge again before the fall. In the fall, officials say, Americans of all ages, including anyone who gets a booster this spring, should get another shot.

[y66]

Eric Topol said:

Should I get a 2nd booster?

The deficiency in our knowledge base is the lack of follow-up, maximal at only 40 days so far, for enhanced protection vs severe illness, hospitalization and death. Surely that’s worth something, and likely will have some durability for a few months. but It probably will have faster attrition than BA.1 protection from the Israeli data we’ve seen so far on infections. So this should be viewed as a temporizing, bridging measure.

I would recommend the 2nd booster if you are more than 4-6 months from your 3rd shot, you are age 50+, you tolerated the previous shots well, and you are concerned about the BA.2 wave where you live, or that it’s getting legs as you are trying to decide. Or if you are traveling or have plans that would put you at increased risk.

It can certainly be deferred, but the question is when is the right time, and whether an Omicron-specific vaccine will have any advantage over a 2nd booster directed at the original strain. The data from 2 animal models (macaques and mouse models) suggests there may not be advantage of the Omicron-specific vaccine but that may not correlate with its effect in people. From my discussions with FDA, it is not likely the Omicron-specific vaccine will be available before late May or June. So you can factor that uncertain added benefit and timeline into your decision.

It’s also fine to wait if there’s a low level of circulating virus where you live and work. Israel will have more follow-up data soon, and for all age groups, so in the weeks ahead we’ll know more about the magnitude, age range (such as age less than 50) and durability of the benefit.

If you had 3 shots and an Omicron breakthrough infection, there’s little need for getting a 2nd booster at this point. You’ve got some hybrid immunity and you can save an extra shot, if or when there’s ultimately supportive evidence for a later time.

If you haven’t had your 1st booster, you’re long overdue to get it. It was lifesaving vs Delta for people age 50+ and vital for maintaining high level of protection vs severe disease from the Omicron family of variants.

There’s a lot of moving parts here! As new, relevant data comes available, I’ll update this post.

https://erictopol.su...new-booster?s=r

[pilowsky]

Hard to argue with Eric Topol since he's married to smerriman!

[pilowsky]

In a study titled "Effect of Early Treatment with Ivermectin among Patients with Covid-19" by Reis G. et al (30 Mar 2022) in the NEJM the authors find nothing.
Must be great to do a study where you set up a null hypothesis, find null and still get a paper in the New England Journal of Medicine.
On the plus side the treatment arm didn't cause any harm.

Reis G et al said:

We did not find a significantly or clinically meaningful lower risk of medical admission to a hospital or prolonged emergency department observation (primary composite outcome) with ivermectin administered for 3 days at a dose of 400 μg per kilogram per day than with placebo. We found no important effects of treatment with ivermectin on the secondary outcomes.

Of course, the authors did note (consonant with the delusional state of ivermectin proponents) that:

Quote

Given the public interest in ivermectin and the support of its use by paramedical groups, we suspect that there will be additional criticism that our administration regimen was inadequate.

I suspect that when they politely say 'paramedical' they are not meaning to include paramedics but are thinking of parapsychologists etc.

This is the problem with alternative medicine in general, it's exactly that, an alternative to medicine.
For reasons that aren't clear, the authors didn't include a "prayer arm" in the study.
I suppose that'll be the subject of the next grant - following on from Francis Galton's work.

[pilowsky]

Publications are starting to emerge that aim to measure the impact of the COVID pandemic.
Here are the findings of a group called "COVID-19 Excess Mortality Collaborators"
published in The Lancet (2022; 399:1513-36) a few weeks ago titled "Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21."

Quote

Findings
Although reported COVID-19 deaths between Jan 1, 2020, and Dec 31, 2021, totalled 5·94 million worldwide, we estimate that 18·2 million (95% uncertainty interval 17·1–19·6) people died worldwide because of the COVID-19 pandemic (as measured by excess mortality) over that period. The global all-age rate of excess mortality due to the COVID-19 pandemic was 120·3 deaths (113·1–129·3) per 100 000 of the population, and excess mortality rate exceeded 300 deaths per 100 000 of the population in 21 countries. The number of excess deaths due to COVID-19 was largest in the regions of south Asia, north Africa and the Middle East, and eastern Europe. At the country level, the highest numbers of cumulative excess deaths due to COVID-19 were estimated in India (4·07 million [3·71–4·36]), the USA (1·13 million [1·08–1·18]), Russia (1·07 million [1·06–1·08]), Mexico (798 000 [741 000–867 000]), Brazil (792 000 [730 000–847 000]), Indonesia (736 000 [594 000–955 000]), and Pakistan (664 000 [498 000–847 000]). Among these countries, the excess mortality rate was highest in Russia (374·6 deaths [369·7–378·4] per 100 000) and Mexico (325·1 [301·6–353·3] per 100 000), and was similar in Brazil (186·9 [172·2–199·8] per 100 000) and the USA (179·3 [170·7–187·5] per 100 000).

[y66]

Matt Yglesias said:

https://www.vox.com/...-book-interview

Bill Gates’ ideas seem good.

After millions dead and trillions in economic losses the lack of focus on preparing for the next pandemic is extremely frustrating to me.