Sunday, October 24, 2021

Are COVID-19 vaccines useful? (2)

I really, really don't like this:

Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination

I picked it up via a tweet from Gabor Erdosi in the aftermath of the excellent discussion he had with Raphi, available on Youtube.

The only fundamental problem I have with their discussion was about original antigenic sin and the above pertains directly to this.

I was very pleased to receive the OAS source paper from Mike Eades (thanks Mike!) and it's a great read. An old paper from 1960, written in the style of the time, giving a basic idea discussed in almost conversational terms by a single author, with enough data to back up the idea, explaining where it came from. I can't see the original paper on tinternet although there are lots citing it:


EDIT location for the first page provided via eugyppius END EDIT

NEXT EDIT Full text here, thanks to Raphi END EDIT AGAIN

So. My fundamental difference in viewpoint to Gabor is that my expectation is that OAS from the mRNA vaccines would be limited to the systemic immune system and the respiratory mucosal immune system would be free from OAS and so able to mount a broad, effective response to produce sterilising immunity to a field infection. Whatever the evolution of spike protein to antibody avoidance, the respiratory mucosal system should stay clean.

The above technique of giving an intranasal live attenuated influenza vaccine at the same time as a systemic IgG inducing mRNA based vaccine appears to trigger respiratory mucosal IgA formation to the systemic spike protein antigen. You "kick" the respiratory system with an attenuated influenza vaccine and the "awake" respiratory immune system "notices" and responds to what should have been a systemic-only spike protein stimulus.

In the UK we already have routine childhood intranasal influenza vaccines. I'm not anti-vax, my kids get the intranasal flu vaccine, FWIW. Assuming mRNA Covid vaccines are made mandatory for children (peak stupidity, but nothing surprises me) I can see that the logistics of delivering both vaccines on the same day might favour doing both at once.

So for kids OAS would be effectively extended from systemic IgG to mucosal IgA. Which might well blunt a correct, broad antigenic response within the airway at the time of a subsequent field virus infection.

This sounds like a very, very, very stupid thing to do.

So it will probably become standard practice, even mandatory.


On the plus side the mucosal IgA might be sterilising, if anti-spike antibodies are enough to kill all of the virus. This will limit time available for selecting an anti-spike antibody evading strain of virus. But the pressure will be still there.

It's like giving a full therapeutic dose of methicillin to a patient with a methicillin susceptible staphylococcal infection. It works. You have to do it. You have to kill the staph completely. But one day you will still successfully select for MRSA... It will happen. It already has.

Friday, October 22, 2021

Are COVID-19 vaccines useful?

Mike Eades updated the current copy of the Arrow to include Alex Berenson's observation that the COVID-19 vaccine surveillance report Week 42 from the UK Health Security Agency (ie the UK Government, such as it is) details that the phenomenon of Original Antigenic Sin is clearly being demonstrated in the UK covid antibody data.

This concept is very simple and predicts that if you are exposed to a single antigen (here the spike protein derived from an mRNA vaccine) your immune system will prioritise a response to that single antigen in preference to other antigens when presented with a mixed antigen soup, as in the whole virus during a subsequent field infection.

So, in double vaccinated individuals you have preferential response to the spike protein over nucleocapsid protein as assessed by antibody titres. Page 23 if you want to have a look:

"recent observations from UK Health Security Agency (UKHSA) surveillance data that N [nucleocapsid] antibody levels appear to be lower in individuals who acquire infection following 2 doses of vaccination."

ie the vaccine screws your immune response to nucleocapsid.


However the UKHSA only monitor anti-spike protein and anti-nucleocapsid antibodies because these allow us to distinguish between vaccine exposure and field infection. Obviously field infection triggers many more immune responses in addition to those against spike and nucleocapsid proteins, none of which need to be monitored to get this information.

As we vaccinate using the spike protein alone we will actively favour the survival of vaccine evading mutations. Boosters will speed this up.

So, are we all going to die?

I think not. UKHSA is monitoring antibodies. These are being surveyed in recovered patients.

"Recovered" is the word. 

Ultimately triple (and greater, eventually) vaccinated people, so long as the vaccine is spike protein based, will eventually end up behaving as though they are unable to even "see" the spike protein, their anti-spike antibodies will be present but will do nothing. Spike evasion will have happened and the selection pressure will no longer be present. Lots of anti-spike antibodies, no interaction with the spike, no further selection pressure.

Vaccinated people will have to run on non-spike immune response, which will still be broad and still work. It may not be as effective as in the non vaccinated, because the immune system prioritises large amounts of useless spike response, but most people will still survive (unless they have chosen to be a poorly controlled diabetic, diagnosed or in-situ of course) as they are doing currently.

In some ways I can see some use for the vaccine and the idea of vaccine passports.

Aside: Of course using vaccine passports for anything, especially to pauperise and exclude the unvaccinated, will come with a sh!tload of human rights violations in addition to the health problems automatically generated by pauperisation per se. This is morally reprehensible and unforgivable. It's happening now if you live in the wrong country. Don't you love politicians? End aside.

At the start of the pandemic certain groups of people were thrown under the bus as regards covid. These are people who do actual work. Supermarket checkout cashiers, bus drivers, garbage collectors, postal workers, truck drivers, construction workers. Others, like myself, were given several months leave on 80% of salary with a big garden during some of the sunniest Spring weather I can recall. So we "let the virus rip" through people who actually do jobs ("essential workers") and paid loafers like myself ££££ of my children's and probably grandchildren's money to stay at home and "avoid" the virus. For a while.

Now the vaccine is here and the virus is in reality being allowed to rip through the rest of society, including the laptop classes. Clearly vaccine passports will actively concentrate vaccinated people in to crowded places and so maximise transmission. The UKHSE report cited above also reports vaccinated people are a lot better at getting infected compared to the unvaccinated, interestingly enough. Provided these people do survive (and most will) then they will end up with a ton of useless anti-spike "immunity" plus enough real immunity to other components of the virus to survive future exposure to that virus. We need this.

That should be enough.


PS I can live without the human rights violations which seem to be endemic at the moment. Or should I say epidemic or pandemic???

Saturday, October 16, 2021

Modelling energy intake (3): empagliflozin

In the aftermath of the of canfliglozin post I picked up this paper via Tucker:

Energy Balance After Sodium–Glucose Cotransporter 2 Inhibition

It's the group including Hall again, with a different drug but still looking at glycosuria as an "insensible" caloric loss. If you feed the daily glucose loss in to their sophisticated CICO derived formula the weight loss over 90 weeks should be 11.3kg whereas the actual weight loss was 3.2kg.

This was correctly attributed to increased calorie intake, reverse modelled to an increase of calories in the region of 270kcal/day. What to do about this?

The best section of the abstract is the conclusion, which sums up the paper:

"Chronic glycosuria elicits an adaptive increase in energy intake. Combining SGLT2 inhibition with caloric restriction is expected to be associated with major weight loss."

Translation, "starve the buggers". Starvation ALWAYS facilitates "major weight loss".

That was 2015. But even then Hall was well aware of the stupidity of this approach, as he detailed in his 2016 publication:

If caloric restriction where a feasible option I guess no one would ever get fat and, if they did, anyone could easily lose weight by caloric restriction, without the risk of fungal necrotising fasciitis (necessitating emergency removal of significant parts of a person's genitalia and possibly surrounding tissues) which comes as a real risk with the canagliflozin or empagliflozin deal. Sadly caloric restriction is generally associated with intolerable hunger and rapidly failing ability to maintain any large caloric restriction. An insight superbly documented Hall et al.

Ultimately in the real world of the CIM, the urinary loss of "x" glucose calories drops insulin. It appears that this drop in insulin releases a certain amount of FFAs from adipocytes, say "y" kcal, but y is never quite enough to fully compensate for the urinary loss x (no reason it should be). So a small amount of food is needed to make up the deficit as perceived by the brain stem. Back in 2015 I guess diabetics were being advised to eat low fat, high carbohydrate diets. So each patient eats a few extra calories, roughly x minus y extra. That food will be around 55% carbohydrate. Which will directly offset the urinary loss per se but more importantly, will increment the level of insulin in the bloodstream.

As insulin is incremented upwards by the extra food, so FFA release from adipocytes will increment downwards and so a spiral of rising food intake, rising insulin and falling FFAs (limiting weight loss) will ensue.

There is some sustained weight loss. I would guess that this is related to the residual fat content of the extra food eaten, which won't raise insulin the way the carbohydrate component will.

Which leaves you wondering if by providing the small food increment needed to off set the x - y deficit in the form of fat, perhaps a much more significant weight loss might have occurred. Not sure 11.3kg would be possible, but it might be.

And of course starvation would not be needed... But perhaps that smacks of LC eating and the CIM too much.