Saturday, December 12, 2020

IgG IgA and sniffing a virus

Basic immunology 101, ignoring T memory cells and cell mediated immunity..

If you contract a respiratory virus it colonises your nose/throat/windpipe. If you are unlucky it will also colonise your lungs and you might well be headed for a week or two in the ITU.

If it doesn't, you get better.

If you are re exposed to the same virus a month later you will not become ill unless you have something very, very wrong with your immune system. But might you transmit the virus still?

You can track the response of your immune system to the virus by tracking serum antibody production. The immediate effect is to generate IgM antibodies. These fade after a few weeks and are used clinically as a marker for recent infection. After a week or so you make IgG antibodies. These are present for a few months or even for life, depending on which virus we are talking about and whether there is continued exposure. If they are "neutralising" antibodies they will actually stop the virus invading cells by attaching to the cell-invasion protein of the virus. They are protective against illness.

There is another class of "poor relation" antibodies, the IgAs. These are mucosal cell surface produced antibodies. They are produced on the membranes of your nose, throat, trachea and possibly lungs if the virus gets that far and you survive.

IgA largely stops the virus becoming re-established in your nose on re-exposure. Neither IgM nor IgG, even if it is a virus neutralising IgG antibody, is going to do this.

Just to avoid controversy (and because the paper is handy) let's look at mice vaccinated against influenza using an adenovirus vector vaccine. The group used exactly the same vaccine in two groups of mice, in one they gave it intranasally, in the other intramuscularly.

Reduction of influenza virus transmission from mice immunized against conserved viral antigens is influenced by route of immunization and choice of vaccine antigen

"Here we demonstrate that transmission reduction is more effective when mice are immunized against A/NP and M2 intranasally than via the intramuscular route"

The intranasal route stimulated marked IgA production. The intramuscular route produced a minimal IgA response. Once vaccinated the group then challenged the vaccinated mice with field virus and assessed the ability of those vaccinated mice to transmit the field virus to non protected mice.

Intranasal, IgA generating, vaccination reduced transmission by 88.2%.

There is nothing surprising about this.

I fully expected the same vaccine given intramuscularly to do nothing at all to reduce transmission but it did, oddly enough, reduce transmission potential by 47%. Of course the question to be asked is whether this 47% transmission rate reduction would allow a vaccinated care worker to safely nurse your granny during an influenza pandemic.

You also still have to ask whether an 88.2% reduction in transmission might make a care worker safe to nurse an elderly person.

An adenovirus vector vaccine will induced an immune response to the protein coded for in the mRNA built in to that vaccine. If injected in to a muscle it should induce IgG in the bloodstream to that protein which, if neutralising, should protect against illness. That's good, but limited.

Contrast that to a genuine field virus infection. It starts in your nose, spreads to your throat and then down your windpipe to give you a marked production of membrane based IgA throughout the airway. It is going to induce IgA production to a whole host of viral proteins, not just the one or two forms of IgGs generated by a vaccine (even if given intranasally to generate some IgA). Some field antibodies will be very useful, some less so.

It seems to me that the probability of reducing or even eliminating viral transmission might be much better from a field virus infection than from a limited antibody response generated by an vaccine, even if given intranasally.

Quite what might happen if you combined intranasal and intramuscular administration, or even gave two doses of intranasal vaccine a few weeks apart are open questions for mice in influenza models. Yes, a model is only a model.

How much of this might be generic to respiratory viruses in general I don't know but I would be amazed if it wasn't.

As always there are a slew of questions which follow on from this concept but I'll stop here with my fondness of IgA inducing vaccines and particularly of asymptomatic infections. Having said that, I would qualify it as a vet. Anyone who has had the pleasure of administering an intranasal vaccine to a 40kg aggressive dog who is voting against said intranasal vaccination with his teeth is another matter. Luckily you can get it in through a muzzle on a good day. 



LA_Bob said...

Thanks very much for the antibody lesson. Clear, concise, and to the point.

karl said...

Great stuff as usual. I'm an old biology nerd - I started reading Sci-American cover-to-cover in the 70's - Saw the work of teasing out how the immune system works. Absolutely amazed at the current hysteria. It is as if all the hard earned research on immunity and viruses is totally lost on the public.

So what strikes me is that the main-stream news seems to not mention anything about T-cell response in relation to vaccines .. The vaccination papers read like legal documents - not sure I can trust them.

Actually, according to WHO's numbers, there are two ongoing pandemics - the T2D one appears to be killing more people..

So I'm troubled by this gap - we have a viral pandemic - similar in scale to the ones in the 50's and 60's ( Asian flu (1957–1958) Hong Kong flu (1968–1969) ) both killed 1-4Million world wide. Then there is the diabetic pandemic - which I think is killing a similar number and yet is not seen as a crisis. This cognitive dissonance bothers me..

My belief is the diabetic pandemic is gaining steam - I've seen the people in the Philippines go from eating lard - to eating imported veg-oil - and getting fat and sick. At the rate this is increasing, I think T2D will kill more people, each year, than what we are seeing with CoVid.

I worked with small particles - I own a particle counter. Originally the CDC said that public masking was "ineffective" - which I think is quite true. My take is everyone will get exposed - masks/isolation or not - exponential growth is exponential growth - Sweden seems quite sane to me - faster is not the same as more - area under the curve matters. 10um pores don't block 100nm virions. Coughs and sneezes go out the side anyway. Surrounded by ungrounded-narratives.

But what is really bothersome - is when they tell at risk people that masks work THAT seems particularly evil.

There is another issue - Probably not polite to ask this, but does having high blood sugar put one's loved ones at increased risk? I have a hunch - I've seen work on viral replication rates vs blood glucose..

In the end - having a healthy innate immune system - which should allow most people to get immunity without getting desperately ill - should have been the public policy goal to strive for - I don't think the best-and-brightest are running things.

I really hope the vaccines work (without injuring people) - I'm tired of the hysteria - I feel like a year of my life was taken from me - I'm a social animal.

cavenewt said...


"Then there is the diabetic pandemic - which I think is killing a similar number and yet is not seen as a crisis. This cognitive dissonance bothers me."

I don't think it's that mysterious. Our particular crowd believes the diabetes epidemic is caused by lifestyle, mainly diet, factors. Powerful economic players have a vested interest in suppressing this view. Also, it's been a relatively gradual event, so it didn't grab attention. COVID-19, on the other hand, has a pleasingly graphic little particle that can be pointed at, universally demonized and, just as importantly, profited from.

The added fact that the effects of the latter (virus) are exacerbated by the former (metabolic damage) might not be recognized for many years. But even when it is recognized, there's still the problem that Western medicine keeps wanting to fix diabetes using drugs rather than lifestyle changes.

"Coughs and sneezes go out the side anyway. Surrounded by ungrounded-narratives."

I don't believe they've ever claimed that masks provide anywhere near complete protection. Since infection risk is largely determined by viral exposure of quantity X time, anything that reduces the quantity factor will help. Someone who is coughing and sneezing shouldn't be out in public anyway, whether or not they're wearing a mask. I don't think you could argue that masks are *completely* ineffective although there could be a debate about the degree of effectiveness. They're definitely better than nothing.

That said, I'm sure hoping that when I ultimately get the virus it won't be too severe, and then hopefully will enjoy a certain amount of immunity. Cross fingers. In the meantime I'm being a good citizen by distancing and wearing a mask.

LA_Bob said...

Hi, Karl,

I disagree about the diabetes pandemic. I think it is indeed seen as a crisis. But it causes cognitive dissonance. The appropriate diet is low carb with saturated and monounsaturated fat. The "preferred heart-healthy" diet in today's terms is "high-glycemic carbs" with mono- and polyunsaturated fat. They pour gas on the fire and wring their hands the fire won't go out.

So cheesy and toxic medication is the only other tool. And it's like beating the fire with crescent wrenches.

Far bigger than the diabetes pandemic but just as bad is the pre-diabetes (metabolic syndrome) pandemic. Same cognitive dissonance. Same result.

LA_Bob said...

Hi, cavenewt,

I've found the masking arguments to be incredibly controversial. Good / useful vs Bad / useless. Studies seem to be contradictory.

Have you seen Stan Bleszynski's November 13 post on masks during surgery? Mind-boggling. And in the comments there are two video links showing the beneficial effect of masks.

Seems impossible to reconcile these things.

LA_Bob said...

Oops. Forgot the link to Stan's post.

Peter said...


I'm a surgeon. I don't wear a mask. I probably have the lowest infection/complication rate in the practice. This is largely because I'm old, experienced and strive for atraumatic surgery (if such a thing exists). I mostly do routine ops and don't hang around! I am also very aware of how seriously controversial the use of surgical masks was when they were first introduced. Another peril of wide reading in the days before 'tinternet!

Since nowadays the covid police actively patrol the practice I sneak my mask down below my chin as I start each op. Surgery goes better if you can see through your glasses. As does placement of an IV line in prep.


cavenewt said...


"Far bigger than the diabetes pandemic but just as bad is the pre-diabetes (metabolic syndrome) pandemic."

But aren't they really the same thing, essentially just different points on the spectrum?

LA_Bob said...


Incredible! For me this has all been a revelation, since we laymen just assume masking up in the operating room is SOP. I wonder if you do much training of the "kiddies". If so, I'm sure they're a lucky bunch. And I hope you've not been bit by many 40kg dogs.

By the way, some folks advocate for masks as reducing viral load exposure leading to asymptomatic immunity (think Japan). When I listened to Richard Breeze I noted he wasn't a big fan of the viral load hypothesis for infection (no "gradient response", I suppose). No end of interesting perspectives.


Having read Taubes, Peter, and so on for years, I certainly think so. But I've not noticed met syn mentioned as a risk factor for COVID except here and maybe some low-carb forums. I'm with Karl that diabetes is or ought to be thought a crisis. It's just that metabolic syndrome seems to be considered as diabetes's "little brother", related but separate. It's really the little brother that is overall the big problem with diabetes just being kind of a subset.

Peter said...


It's becoming more and more SOP driven. To the point that nowadays patients have to go home, cat or dog, after routine operations such as neuterings wearing a head collar. Even two years ago that was unheard of unless the patient was clearly a wound licker +/- had clipper rash from site preparation. My plan has always been that my surgical repairs should be "patient proof" ie, spay wounds should be small, non bruised, closed without excessive tissue tension and have meticulous apposition of the skin edges using buried subcutaneous sutures and certainly no skin sutures.

I certainly try to explain what I'm doing to the youngsters. But I have a shitload of stuff going in my head almost every second. It never stops. Does this suture align the skin well via the last suture position? Will they snug down neatly as I tension the suture line at the end of the incision closure? Will the knot bury? Do I need to adjust the final suture placement to improve knot burial? Minilaparotomy for cat spay, might be 4mm long. Reach in with very narrow forceps and exteriorise some fat. Is this omental fat? Put it back. Perirenal fat? Aiming too high. Uterine broad ligament fat? Pay dirt. It should have a uterus attached somewhere, just about THERE! I am an expert on recognising fat depots within the abdomen. For bitch spays it is finger recognition of fat types that I use. I need a hole big enough to get a finger in. And back out again with a uterus hooked up by it.

I think about this stuff all the time, while backing up the nurses if I pick up that something about the anaesthesia is twitching them out. While talking kayaking/rowing/running/Christmas/gin/vodka/atropine/Michael Jackson and propofol.

I try very hard not to indoctrinate the kiddies or lay down the law, other than to avoid dangerous choices and to absolutely avoiding pissing off the nurses (rule number 1).

Sadly I also can't help but point out that although they were taught (by a surgeon) that wounds heal from edge to edge so big holes are fine, from an anaesthetist's viewpoint pain comes from end to end. As does infection risk. And don't piss around with buprenorphine for pain control. If you are still learning your surgical techniques you will be traumatic and you patient will appreciate a pure agonist opioid drug. Top it up if it's not working. Check it really is working. If they are dribbling, they feel sick. Give marotpitant. You would want it.

God, I must be awful to work with!


cavenewt said...

Having read Hyperlipid for many years, I've come to respect Peter's opinion (not a guru! Never a guru!), as well as some regular commenters, and on several subjects that I thought were more or less settled they have provided cause for re-examination. So with the mask thing, I'll just hunker down in my remote desert and hope the whole mess blows over eventually.

Peter said...

karl (and maybe Eric in previous comments),

Stick my neck out. Death from COVID-19 is a symptom of diabetes. I have mentioned to Eric that a medic wouldn't recognise metabolic syndrome if it but them on the butt.

If a person has a completely normal OGTT that does NOT rule out diabetes. If that person was buying that normal OGTT result at the cost of markedly elevated insulin levels, that to me is "diabetes in situ". Joseph Kraft was spot on. Without an OGTT with insulin I would accept NAFLD as a reasonable surrogate for "diabetes"... And obesity as a poor relation. Mike Eades posted a string of images of Johnny Prine when he died of COVID. Each image, over the years, looked more and more like a diabetic. To me anyway.

The mention of glucose and viral replication is interesting. I mostly come at it from hyperglycaemia being synonymous with immune dysfunction. There are a string of papers on this, the first to drop out of Duckduck was this one, neutrophils eating staphylococci. (needs scihub)

and this one second

Unless glucose is elevated, at which point neutrophils go on vacation. Hence diabetics being more than a little prone to foot infections and where that leads. I think the observation in people with COVID-19 is that an admission BG over 10.0mmol/l suggests progression from ward to ITU to morgue is likely. Below 10.0mmol/l, you might get to go home.


Peter said...

Heehee, that will be "bit them on the butt" not "but them". Bart will be displeased.


Frunobulax said...

Just a few decades ago we were convinced that we were all sinners and all that went wrong in our lives is gods judgement for our sins. Public belief that diabetes comes exclusively from sloth and gluttony isn't too surprising then, is it?

Glucose control/metS and COVID is mentioned here and there, for example and I've also googled that a handful of studies are underway how keto diet affects the severity of COVID19 infections, unfortunately all of them are scheduled to end in summer 2021 or later.

karl said...

Quite agree - in the end I think the numbers will be available - one can link the end population death rate with the T2D rate. I think the population death rate has everything to do with T2D.

Where we might differ a bit is the 'why' of seasonality of Corona Viruses - which is well known. I think this is from the changing levels of average vit-D in the population. A couple of virus papers from before the hysteria:

My take is the public policy has been horrible - telling people to wear masks and not advising people control their BS or consider vit-D.

A question for a veterinarian - humans make vit-D in the skin - what is the corresponding source in furry animals - cats - dogs - must be dietary? What are normal blood levels in cats and dogs?

I think masks might actually slightly slow the spread - but not by filtering - but because people don't want to see people in masks - I don't want to go out (and I miss humanity).

I've stuck a particle counter in the output of HEPA filters that are supposed to stop 300nm particles - yet some get through.

I know people confuse um with nm, but the scale is off by 2 magnitudes - even virus lab level precautions fail. (surgical masks claim 10um - but the particle is 100nm - the ratio of volume to surface area of the water droplets also means they are very short lived .. but I digress )

If people are in the room it is impossible to keep things clean on a nm scale - ask anyone that is responsible for semiconductor clean rooms.

A last ditch attempt to put it in perspective - you have seen the tiny drink umbrellas that come with mixed drinks? You can go out in a downpour with one - does it make a difference? You will still get wet.

In the end, we all get exposed to community viruses - the area under the population death rate curve is not effected by the policies - no obvious inflections in the death-rate graphs - but I think that area is dependent on the quality of the public innate immune system - something we HAVE control over - varies a bit from place to place. There has been a total failure of sane public policy - the cooler heads are afraid to speak.

Peter said...


Ha, I believe one of the most clear cut things we know about god is that she likes beetles, judging by the prevalence and variety of the species on earth. I might guess that a second defining feature is that she doesn't much like people who eat sugar or seed oils.

The keto diet work will be excellent but might well be markedly confounded by the love of omega 6 PUFA in the diets, especially those for people. Got to keep everyone Hearthealthy. But the normoglycaemia and inflammasome suppression might be enough...


Peter said...


I believe that furred animals secrete their 7-dehydroxy cholesterol in to the oils of their coat, get it UV converted to D3 via sunlight, then ingest it by grooming.

The seasonality of respiratory infections is fascinating. The season usually peaks in January and not even I, given a lovely garden and fondness for sun bathing, am making any D3 in January in the UK, even if it is warm enough to be out there (which it occasionally is). Or does the peak occur then because by this time all of the people who entered winter hypovitaminaemic secondary to dermatological advice have been ill and recovered/died, while non hypovitaminaemic individuals will make it to March okay? ie is this just a Gompertz curve running only through the susceptible section of the population?

I was surprised by COVID-19 patients’ excellent response to vit D supplementation. Occasional attempted use of supplemental D as an adjuvant to managing mycobacterial infections in cats was markedly unrewarding (so I’m told, no case report ever got published).

In the UK we introduced masks at the absolute rock bottom mid summer nadir of the virus. It was based on expert opinion and inter-country comparisons. We know how well they worked out for the cholesterol hypothesis. Mask use is essentially a religious diktat, certainly in the UK.

I have to say that in the past I have worked in practices where surgical mask use was obligatory in theatre. But these were surgical masks, tied tightly in place and fitting well enough that my glasses didn’t steam up. They were still a pain and made no discernible difference to my post op complication rate but I could still see. Anyone who believes a little rectangle of paper on loops of loose elastic over your ears does anything is deluded. Obviously true surgical masks (which I suggested to my head nurse might help with glasses function, seeing as I’m mow supposed to wear a mask at all times) are a idyllic dim and distant memory in these days of the blue paper rectangles…


Frunobulax said...

I can understand where the mask hype comes from. Apparently we need a certain amount of viral mass to become infected, and masks clearly will absorb something. The question is how much. They stop working if they become wet, and will filter some percentage of viral particles if not.

And now the insanity starts. We use homemade masks that probably don't absorb anything, and masks that are designed to stop only spittle but not aerosols. No one questions their efficiency. But IMO it all comes down to one simple fact: We trust too much in science, and science doesn't regulate itself. Trust is obviously OK for "normal" people (just as I trust engineers to design bridges that allow me to safely cross a river), but I'd expect some basic thinking on the part of doctors, or science editors for big news agencies. Which of course rarely happens. All editors do is to parrot whatever they read in abstracts, if they even read the abstracts.

Case in point: The biggest private news outlet in Germany (Spiegel) had an article about masks. The one study they cited for their efficiency was a hamster study, where they separated infected hamsters from healthy hamsters with mask gauze. To separate 2 hamster cages, one would need at least the gauze surface that is used in a human mask even if the cages are tiny. OTOH hamsters are what, 50 grams apiece? So the amount of water exhaled would be at least 1000 times less than what a human exhales, so this gauze will probably stay dry while masks worn by humans get wet. Beyond ridiculous to even include such a study. The only other study they cited was about FFP2 masks in a hospital setting, where personnel likely changed masks in regular intervals. And yes, I do believe that a FFP2 mask will do something if worn only for half an our or so. But it's again ridiculous to compare this with selfmade chiffon masks.

We all would be better off if people would ask some basic questions. Like, if a single marker out of thousands (like cholesterol) can really more important than total mortality rate. But I digress :)

raphi said...

"I believe that furred animals secrete their 7-dehydroxy cholesterol in to the oils of their coat, get it UV converted to D3 via sunlight, then ingest it by grooming."

I don't even care if it's true or not. I simply appreciate the beauty of the idea.

Peter said...

raphi, it's probably something I was "told" in a lecture decades ago. Sadly it may be part of the 50% of medicine which turned out to be incorrect, or at least out of date!!!!


Peter said...

Fruno, we abandoned all science in this pandemic somewhere around February/March in the UK. Though Witty and Valance were doing reasonably well until Boris pooped his nappy and locked us down in March. Now everyone involved is just a politico...


Dr. Rob said...

Hi Peter, I would like to raise some concerns about the mRNA vaccine, which I have not yet seen discussed. This involves the interaction between microRNA and mRNA in the cytoplasm causing dysfunction in the mitochondria and the development of cancer.

Energy and information are required for the production of anything and everything - including the proteins that make up T-cells and antibodies and naturally the Human body has evolved a system to facilitate this process.

microRNA or miRNA interact with mRNA in the cytosol of the cell to regulate the expression of genes - effectively acting as epigenetic controls.

This production process requires energy which predominantly comes from the mitochondria ETC - consequently there is a crosstalk between the miRNA and ROS and mitomiRNA in the mitochondria to effectively allow energy supply to match energy demand in the production process.

This is how a highly evolved and efficient system works - it doesn’t waste valuable energy and resources.

I suspect the injection of an mRNA molecule connected to a lipid nanoparticle is going to cause some disruption inside the cytosol and dysfunction of the mitochondria.

When things become dysregulated the system starts to malfunction and dis-ease manifests.

Altered miRNA expression is linked to excess ROS and the pathological features of inflammation. This then leads to the development of chronic diseases like cancer, CHD, diabetes’s and dementia.

Indeed, there is increasing evidence that miRNA’s are involved in cancer development via energy reprogramming and allow cancer cells to adapt to an hypoxic environment.

For example, miRNA-1246 is associated with most of the major cancers - breast, prostate, oesophageal, colorectal and also metastatic spread.

Significantly wrt SARS-CoV2 miRNA-1246 is also a regulator of ACE2 expression in the endothelial cells of the lungs

As well as B-cell activation in SLE

Across the full SARS-CoV2 genome it has been predicted that miRNA’s target 113 different locations - the mRNA responsible for the spike protein used in the Pfizer vaccination will undoubtedly be targeted by miRNAs - but which ones?

I cannot find any information on this - which is a concern - because in order to predict the possible long term effects of the mRNA vaccine we need to know which miRNA’s are stimulated and therefore which proteins get produced.

I did find out that in the moderna vaccine miRNA-1273 is used, however this family can produce 100s of different proteins and it is not biologically plausible that only one miRNA gets activated.

I fear any increase in cancer will be lost in the noise of reduced screening and delayed diagnosis.

Frunobulax said...

Oh, I wasn't aware that we already know for a fact that homemade masks don't work.

This is with a dry mask: "Surprisingly, wearing an unwashed single layer t-shirt (U-SL-T) mask while breathing yielded a significant increase in measured particle emission rates compared to no mask, increasing to a median of 0.61 particles/s. The rates for some participants (F1 and F4) exceeded 1 particle/s, representing a 384% increase from the median no-mask value. Wearing a double-layer cotton t-shirt (U-DL-T) mask had no statistically significant effect on the particle emission rate, with comparable median and range to that observed with no mask."

Passthecream said...

There was an early report back when masks were more of a novel idea and not mandatory anywhere in USA, UK, etc., from one group of makers who had access to a particle testing machine. Their suggested effective form of diy mask was made from two layers of suitable fabric with an insert between of a polyester fabric known as shop towel. These worked as well as any of the P95 type masks made from electret charged fabrics, also a polyester I think. Supposedly the electret nature rather than the pore size traps particles much smaller than pores and provides attenuation. Apart from the core argument about whether the right mask provides a useful barrier function, the way most people misuse and abuse them obviously negates any benefit.

Passthecream said...

On the metsyn vs infection front, lots of unanswerable questions at this point in time but a case of less harm in general by following useful glycemic lowering practices. But I recall a discussion about Metformin the first drug of T2d choice, not ultimately providing any mortality benefit. Whether that's because the glycaemia benefit was outweighed by toxicity or ???? I sure would like to know!

cavenewt said...

@Frunobulax "Oh, I wasn't aware that we already know for a fact that homemade masks don't work."

Was that sarcasm? Because I looked at that study pretty closely and while the homemade masks using T-shirt material don't work at all well, they also conclude "These observations directly demonstrate that wearing of surgical masks or KN95 respirators, even without fit-testing, substantially reduce the number of particles emitted from breathing, talking, and coughing." In some of their tests the paper surgical mask outperformed even the N95.

All of the homemade cloth masks I have are made of regular woven cotton fabric, two layers, none of them are T-shirt material. However this kind of fabric wasn't even included in that study. I tend to use the blue paper masks most of the time anyway for various reasons.

Please note, I am not being argumentative in favor of masks. I'm required to wear one when I go out so it doesn't matter what I believe.

Passthecream said...

.. by mortality benefit of course I mean lack of mortality benefit!

Eric said...


That's hardly a double blind experiment, is it? And Peter has given alternative explanations, such as the sutures being better because the surgeon can see better.

LA_Bob said...

To the subject of Peter's post, I'm curious about the implication of missing IgA antibodies in vaccinated people. Peter believes such people may still acquire and spread the virus.

Does this mean such people will also have mild, cold-like COVID symptoms? Will they test positive on PCR if they are swabbed?

If so, is there a risk this puts the vaccine's effectiveness in question, true or not? If so, the government attitude may be, "The lockdowns will continue until herd immunity improves."

cavenewt said...

Probably TMI but...
"Effects of mask-wearing on the inhalability and deposition of airborne SARS-CoV-2 aerosols in human upper airway"

LA_Bob said...

This article is interesting. It reinforces Peter's post about IgA antibodies. And if I'm reading it correctly, it suggests a "wild type" infection triggers a broader immune response than the one addressed by a typical vaccine.

"Looking past the critical receptor binding domain of the spike protein, the RBD, many other possible antibody targets are now coming into better view. Recent study of the human leukocyte antigen Class II immunopeptidome has revealed that dendritic cells of the immune system display peptide fragments that span the entire spike protein."

karl said...

@peter and Ralphi - vit-D in fur oil

Ralphi said it very well - that sure is an attractive narrative. Now I will dream of a Mass spec of cat fur oil - how much is digested - Why do animals groom? Why did we lose our fur? Did this play a roll in the human IQ explosion?

I'm sort of a math guy - if I am almost certain to get exposed anyway (CDC says R(0)=5.7 ) - why should I wear a mask? Even if masking could magically cut the spread in half with gaping 10um pores - we will pretty much all get exposed. The death data just doesn't show any inflection with the application of masking - but slower isn't less anyway.

But it isn't even about the virus - it is about a T2D pandemic that has created a sickly population with poor quality innate immunity. Here in Kansas - plenty of T2D cases - we now have a higher population death rate than Sweden - that didn't mask.

Of course there is the unintended consequences of the masking - the social isolation it creates - and the real consequences isolation causes that has been deleted from the narrative of hysteria and what passes as public policy calculation. Isolation causes real deaths - that apparently are not to be counted.

@Dr Rob
Interesting -- Makes me think of the all cause death rate with the iRNA forms of cholesterol (miss)treatment - not that such a detail has stopped the sales.

The trade off between a vaccine and the benefit is always a muddle.

Ferinstance - I have idiopathic SFPN - they don't know why - I see a bit of hand-waving about the auto-immune - but I'm quite sure they don't know. I didn't have SFPN before I started getting flu shots - might be? could be? but I am absolutely positive that I don't know and can't get access to data that might be interesting. Anyway - doubtful theory but.. - but my point is that risks are always very hard to measure - what every I do will probably be wrong. Some risks don't show up for decades (reminds me of ranitidine ). I don't think what the public is told about vaccination risk is exactly forthright - there is some hand-waving - yet I am far from an anti-vacer. The public is not good with statistics - consistently miss judges risks. I think vaccines do mostly net good - but think there is a bigger uncertainty than is generally accepted.

This time - things are rushed - political - hysterical - so I certainly won't be first in line to get a CoVid vaccine - (I don't have the T2D risk factor) - I think when they start pushing vaccinations, CoVid will be finished with the seasonal hump anyway ( I expect to see a small hump again in a year - will they replay the hysteria?).

Eric said...

Well, here's a summary article with plenty of illustrations, animations, links to animations by El Pais and researchers and links to plenty of research papers. I have not followed all the links.

Anyway, they take a stance of always wear a mask when indoors with people outside of your own household, and they are not a newspaper known for crusades.

Eric said...

@ cave

Thanks for this article:

What does TMI mean? I just skimmed the article, and the concept of getting more virus deposition in some places depending on mask type seems novel and solid, so will need to read carefully.

Eric said...

The El Pais article as linked in the Zeit article:

Frunobulax said...

@Karl The Sweden differences are overblown. They dramatically reduced social contacts as well, the only difference is that the government didn't order a lockdown. (But just a few days ago I heard that they asked neighbours for help, as their ICSs are filled to capacity and they don't know where to go with their sick.) Assuming that masks have little effect, the reduction of social contacts was the driver for keeping infection numbers low, where there was no big difference between Sweden and, say, Germany. But incidence of metS is a lot lower in Sweden (when I was there for the last time, maybe 10 years ago, there were hardly any obese people), and they used to consume more butter and less omega-6.

So it's really tough to draw any conclusions solely based on the number of hospitalizations, for example.

@Eric Be aware of observational studies. We've seen dramatic increases in Germany where masks are worn, and we've seen the virus controlled in Asian countries where masks are worn. Can't lok only on the latter and claim that masks are responsible for the decline of infections.

Corona has some fairly unique properties,especially the fact that the main cause of transmission are aerosols and not droplets. So you can't really compare it with other viruses. But that's what almost all pro-mask studies do.

The key issue is that almost all mask studies focus on droplets and not on aerosols, including all the studies that the Zeit references (although I only glanced at them). Cotton masks will certainly reduce the amount of droplets, but not the amount of aerosol. Most COVID specialists are convinced that aerosols are the main driver of infections, especially in superspreading events. So a reduction in droplets won't help a lot.

I do believe that surgical masks reduce the amount of virus spread, for a while. OTOH I have little faith in homemade masks.

LeenaS said...

@Karl and others as well.

Sweden is an interesting example. It should have had infection rates similar to Norway and Finland, as the societies are similar (not densely populated, with good infrastructure, and people living mainly in small households). So far it has failed almost completely. And this has happened in spite of the fact that in Sweden the restrictions have been as strict or stricter than in its neighbors - apart from two months in the spring. Right now infection rate in Sweden is similar to USA, and the death toll about ten times higher than what is that in the neighbors.

None of the three nordic countries have compulsory masks, but recommendations vary slightly as of now. In Finland and Norway masks are strongly recommended off-home when visiting indoors with other people around while in Sweden the (rather recent) recommendation is only for care facilities. Distance working, distance education, closed down public gatherings and strong recommendations not to meet with many people are very similar. The only big difference seems to be in the attitudes, i.e. politics. FHM in Sweden is very, very unwilling to say that their former strategy failed.

However, both the first wave and the second vawe in Sweden are roughly 10 times larger (and mor fatal) than in Norway and Finland.


Eric said...


I suppose we are on the same page then, homemade masks are for show, surgical should be the minum required. And don't get me started on those clear plastic masks...

@ Leena:
In general, the higher the (undetected) prevalance of the virus, the harder the restrictions have to be to achieve the same infection rate at the end of the observation period.

The mystery here is that supposedly (if we believe Dr. Sebastian Rushworth, for example), the virus had all but disappeared by August, which he put down to herd immunity having been attained.

What is your take on why it spiralled out of control again in Sweden in fall?

I think in Germany, it was complacency. We got through the first wave quite well and were way too slow in closing down restaurants, which we should have done with the first cold spells in September, cracking down on rule breakers, doing smarter things about schools and public transport, maybe restricting shops earlier.

Now we are creating new hot spots by having shops close earlier (at least in two states because of the curfew) and concentrating everyone in supermarkets and drugstores which are allowed to continue selling stuff that folks used to get in specialized stores. Madness...

LeenaS said...

True. In Sweden and in spring the virus was strong mainly in the capital region, while this time it is all over the country. E.g. in Gothenburg virus is detected in waste waters with some 80 fold the spring concentrations, so all cannot be just more testing now. And, unlike in UK, the hospital capacity is already streched out, according got Swedish media. 2500 beds occupied by covid is more than the worst figures in the spring. Moreover, lots of staff is missing, since many resigned after the hard spring, and all were told then, that the second wave would not affect Sweden.

The situation up here tends to be easier in the summer, when you can meet outdoors; it was easier also here in Finland. After that in Sweden, which claimed to have no restrictions at first (not really true then either)... oh well, since September new recommended restrictions started to come one by one, almost casually, but no one really pushed for them. "Do as you wish, but think sensibly" it was said. And it did not help at all, it seems. Maybe because the thing was said to be over.

And, what is worse in terms of general attitude, since August the Swedes have reported casualties in e.g. WorldOmeter unlike any other western country, backdating the reported deaths to the actual date, instead of reporting them as a number for the day. This way the numbers must have looked very promising to anyone looking and comparing: the last two weeks look always as if the worst happened two or three weeks ago, because of the delay. But it did not, and it has not. ... and over 150 casualties a day, as reported lately is a lot for a country with only ten million citizens.

Future will tell more, I guess?

LeenaS said...

In general, I do not think this is a mask issue, although I do wear one indoors when not at home. I agree with Peter on the blood sugar issue, and since we manage that with kwasniewski'sh style, the mask is just one more trick to protect others. I may or may not get infected one or more times, but I do not worry about that. Yet I'd hate to know that I've infected others.

My mask is most often an old big cotton handkershief folded in three layers, which I attach with humble rubber bands around the ears. Old folks left a couple of dozen of those, so it is easy to throw them to laundry after each use. Much softer to skin than these paper thingies. And a lot less waste : )

cavenewt said...


TMI = Too Much Information

Peter said...

Dr Rob,

That’s interesting but it’s a field I know nothing about. Any long term effects will be hard to pin down I guess, especially if vaccine uptake becomes ubiquitous. I look forward to the phase 3 trials being completed and reported.

Pass, metformin is undoubtedly a longevity drug, certainly in animal models. It’s comparable to modest dose caffeine, low dose alcohol, glucosamine and a few others which I can’t recall off the top of my head. Median life span increases by about 15% and maximum lifespan extension seems more hit and miss. Compared to something like knocking out the GH receptor in mice the effect is trivial, but then you still have functional GH signalling, which has some undoubted benefits. The other issue with metformin it is normally given to people with insulin resistance. Until very recently this has been combined with the worst possible dietary advice imaginable for someone with insulin resistance. You also have to avoid B12 deficiency with metformin!


Dr. Rob said...

The problem is the placebo controls in the trials are being offered the vaccine and the vast majority will no doubt accept, thereby nullifying much of the data in phase 3!

Peter said...

Well, that might delay me accepting an offered vaccine! I was thinking 2022 or 2023 might have been a reasonable time at which to consider whether the vaccine might be safe and effective. Over the years I have lived through the occasional drug booboo. When a new NSAID is marketed I rush to wait 3-5 years before trying it on a few patients. Some of the problem drugs I had actually finally accepted until fulminating hepatopathy convinced me that my favourite NSAID was potentially lethal. All three dogs survived. Yes, I did fill in adverse reaction reports. That one was carprofen. I still remember flunixin too.


Dr. Rob said...

I remember in the early days of CoX 2 inhibitors falling for all the hype surrounding Pfizer’s Celebrex -they ended up with a $2.3bn fine for mis-promoting medicines and paying kickbacks to doctors. You know what they say; “fool me once, shame on you - fool me twice, shame on me!”

karl said...

I see the posted mask paper - I read it -- please read what it says:

"Wearing a mask significantly reduces particle penetration into the lungs, regardless of the filtration efficiency of the mask. Wearing a 65%-filtration mask can reduce lung deposition by three folds for particles of size 1 µm–10 µm."

Can you understand the numbers? um is 1000 x bigger than nm....

The paper actually says surgical masks work for particles bigger than the particle - exactly what I said. The CoVid virion is about 100nm -- NOT 100um.. This is with a REAL mask - and assumes people are not coughing or sneezing out the side -- yet it still doesn't work. Would you tell someone at risk that they are protected? Is it moral to spread such misinformation?

Yes, I know people believe the masks work - I've suffered wearing them just so I don't scare people. But people are wrong about a lot of things - almost half the people in the USA believe in ghosts, many young people believe CoVid is the biggest risk in their life - not car accidents..

I know people WANT to believe the masks work - WANT to believe they have control over their fate - I feel for them - I appreciate those that think they are helping - but BS is BS.

@Frunobulax - the confounding death-rate data between countries - you think it might be explained by metabolic health? Something that could/can be changed? Wearing a mask won't effect the effectiveness of one's innate immune system - other things can. To think that the modulation of R(e) isn't driven by innate immunity - I would need to find a new explanation for the seasonality of corona and influenza viruses.

Seasonality causes obvious inflections in the death rate - masks don't.

altavista said...

So I get you're on taking it hehe
Resistance is futile

Passthecream said...

Karl, I think a single virion cannot live very long in free air and instead you need to consider aerosol size distributions. These are in the 10s to 100s of microns so well within the filtering range of a well made mask, thereby providing an attenuation factor. This paper is about sneezes, plenty of other data around to be gleaned:

No-one to my knowledge has done the experiment to work out a dose-response curve for CV, or if there is one maybe not even for flu but it is plausible there might be one and if so it would be highly non-linear. When two masked individuals face off against each other, the attenuation factor is squared so even a measly 20% effectiveness equates to a nominal 36% mutual effect, moving down the usual non linear curve that is significant. With your particle test you would approximate that with a mask over the source AND a mask over the detector.

All that aside, another aspect of metabolic health involves getting out in the fresh air away from crowded spaces with stale air. And even in interior or crowded public spaces decent well circulated air supplies with UVC and electrostatic filtration and sterilisation, HEPA filters etc. will make a difference.

Eric said...

@ Karl, exactly what pass said: the virus needs aerosols or droplets to travel, and it is those that get filtered, not the virus itself which wouldn't last a few seconds before drying out

@ all, so what do you make about the new virus mutation? reporting since BoJo's press conference sounds pretty dramatic.

Passthecream said...

Well, viruses mutate rapidly. And if CV can achieve greater infectivity via mutation in one place, there is enough of it around and enough infected people that it will happen in other places soon enough.

I'll be staying where I am thanks, a long way from anywhere! I noticed that with a population approx twice that of Sweden Australia has an order of magnitude fewer cases in total. Also whatever the Taiwanese are doing, that seems to be working for them better than anyone else.

Frunobulax said...

@karl Too many counfounders to be certain. Obesity rates are readily available, and Sweden has few obese people (, but a lot of them are overweight. So they will certainly have metS, but probably not as bad as other countries.

Other cultural differences could affect things a lot. For example the prevalence of aircons in restaurants, schools and hotels, simple things like are people having their lunch outside or inside, stuff like this. LOTs of people in Stockholm travel by bike and not public transport.

Be very, very careful to draw conclusions based on (symptomatic) infections and death rates in different countries, if you aren't sure that both health system and lifestyle are different.

Dr. Rob said...

Eric this is not a mutation - it is a variant - of which they have already found thousands - this particular one was first identified in September.

It wasn’t more infectious then - so what’s changed? - The environment changes - Perhaps, people’s immune systems have weakened in the 2 months since UVB disappeared in the northern hemisphere and vitamin D levels have dropped reducing the T cell response - expect more of the same over the coming months until UVB reappears again in March/April.

Justin said...

I assume the N95 masks are made from some type of polyester. Wonder if it's doped with a wetting agent to overcome the hydrophobic nature of polyesters. If not, I could see this as a problem and possibly facilitate the break-up of larger droplets into smaller if there is a significant pressure gradient. Cotton masks,otoh, wouldn't elecit the same hydrophobic nature of pretreated polyester. I would love to do research on this. I have spent some time making experimental filters from our nanofiber process. It was cool getting to play around with functionalizing the different materials depending on the application. That being said, I'm still far from a filter expert.

Justin said...

Dr. Rob, I'm building a uv b coffin stat, so I can continue to get a nice daily dose. Lol! ;). Btw, thanks for posting the link.

Dr. Rob said...

It always struck me as madness that some European countries mandated masks in the middle of summer - for what is quite clearly a seasonal virus- for many people the face is the only part of their anatomy that ever gets exposed to the sun and even then it’s smothered in factor 50 - no wonder vitamin d deficiency is now the most common vitamin deficiency in the world!

My hypothesis is that vitamin d is stored in the fat cells as an evolutionary adaptation to survive the long cold winters. Fat loss during the winter months due to diminishing food supply would have released vitamin D to support the immune system. Modern lifestyles and in particular over indulgence during the Xmas period will prevent this release of vitamin D and we can therefore expect an increase in infections in January. The environment really is the key to health.

Justin said...

Dr. Rob, My thoughts exactly on the masks/summer thing. That was our low hanging fruit opportunity to also build up immunity when when people are less suseptable due to vitamin D or whatever imparts better immune response.

Interesting idea on liberating D during the low UV B/food availability months. I have been practicing 18 hour internment fasting for well over 10 years now. At the very least, Monday through Friday. I think tissue turnover on a regular basis is important. House cleaning through regular autophagy. Being in the feed state all the time just doesn't make sense to me from an evolutionary standpoint.

cavenewt said...

Eric and pass, thanks, it has been my understanding also that a virus particle doesn't just float around by itself – it hitches a ride on a larger aerosol or droplet.

Very interesting about vitamin D being stored in the fat cells. Of course other things are liberated during fat mobilization, like toxins and PUFAs. Nice to think of some good ingredients in there too.

Passthecream said...

I suspect that vitD is like vitA, only gets moved out to the periphery when the liver stores are full, nicely packaged etc. But A and vitD are mutually antagonistic btw. I have several refs somewhere ( where?) but these are easy to search and find anyway. Just get more sunlight on bare skin and stop eating so many leafy greens and sweet potatoes.

Passthecream said...

Justin, the P95 polyester fabric is specially woven and treated electrostatically, that's what I meant by 'electret' up above. (Just like in an electret microphone, ie a more or less permanent stored charge separation in a dielectric.)


Passthecream said...

Cigarette smoke aerosols are within the size range of interest:

I haven't made the experiment of wearing a mask in the vicinity of a smoker but I do recall just how pervasive that smoke is, you can smell it a few feet away in the open air if unlucky. It's a good model of what we're up against.

Passthecream said...

I'd be interested to know how a 'variant' is not a mutation. Is it wearing different coloured socks?

We are all mutants.

cavenewt said...

"I haven't made the experiment of wearing a mask in the vicinity of a smoker but I do recall just how pervasive that smoke is, you can smell it a few feet away in the open air if unlucky."

A few feet away? I can smell it across the street. If you're a nonsmoker, cigarette smoke is godawful. Maybe if we could get the virus exhalations to smell as bad, it would be easier to avoid.

Eric said...

@ Dr. Rob, Justin: The masks outside thing only makes sense in crowded surroundings. Not sure what the rules were in Italy this summer. In Germany masks outside became mandatory only end of November and only at farmer's markets and in pedestrian zones and outside of train stations etc. In summer, the only instance I came across was a local regulation at the Münster farmer's market which tends to be very crowded.

As for a light source to make Vit. D in summer, I would use narrow band UV-B (311 nm), probably the best compromise between Vit. D potential and low skin cancer impact. I have used a handheld lamp for a few years but never had the courage to use it for more than a few minutes. I have bought two 100 W tubes, though, which are sitting unused.

@ Pass: I would love to read your references about Vit A and D antagonism. Biologically, it does not make sense to me right now.

Passthecream said...

Eric, I will search. I recall that vitE and vitA are also oppositional. The oil solubles are strange but vitA is strangest of all.

Passthecream said...

Here are a couple of links but not the one I was thinking of. The retinyl acetate form there is a bit nasty compared to the usual palmitate or stearate esters.

Passthecream said...

Justin said...

Pass, Thanks for the link! I'm familiar with electrostatics and tribocharging. We used to use HV power supplies and coronas to charge the webs so they would pin/align better. Pretty cool stuff. Looks like they are probably using a gradient filter with all the layers, so as not to blind the smaller pores. Still noodling the idea of either plasma treatment or adding a wetting agent to the polymer and allowing it to bloom to the surface. Not sure if it would be better to have some hydrophilicity in there like you would probably want with a water filter or an incontinence pad. I guess if they stay with the hydrophobic quality of polyester/pp it would just act as more of a shield. I guess the electrostatic charge might potentially overcome the hydrophobic nature of the polymer assuming a liquid encapsulated virus is still attracted. Otoh, I have tribo charged polymers and they still seem to repel water.

We actually made our own masks back in April from merv 15 bag house filter material and some other layers. Treated it with an antimicrobial/antiviron based on the literature. We got favorable results for bacteria, but my boss didn't want to pay for the viral data. Ours are microwavable too. Lol!

Justin said...

Eric, that's cool on the lamps. We are actually looking at making our own aging cabinet for a contract at work and have been looking at lamps. Do you have a link to the brand you used? It would be nice to figure out what the safe equivalent dose would be. Abviously time/distance are your knobs if wattage is fixed.

Justin said...

Pass, good info on the cigarette vapors. I might do some experiments at work with our in house masks and a N95. Wonder how vaping vapors compare?

Eric said...

@ Justin:

Philips seem to be pretty much the only vendor of ultra narrowband UV-B (TL-01 series). Fortunately, they have a pretty good library of pertinent studies.

When I looked into this, there were also Ushio and a vendor from Eastern Europe but AFAIR, their spectrum was not as clean.

This is what goes into handheld lamps:

a broader product overview:

This is their literature download. Googling will also find several independent papers:

Justin said...

Eric, thanks a million for all of that. Can't wait to dive into that literature. Was telling my boss about it today.

Passthecream said...

Justin, fyi, a newspaper article about testing hospital airflows with smoke:

Passthecream said...

Dr. Bob --- hard to know who to believe ---

"Scientists, meanwhile, are hard at work trying to figure out whether B.1.1.7 is really more adept at human-to-human transmission—not everyone is convinced yet—and if so, why. They’re also wondering how it evolved so fast. B.1.1.7 has acquired 17 mutations all at once, a feat never seen before."

Eric said...

@ Justin: just reread your earlier post. What is it you want to age? Narrow band UV-B is not the best for aging. Actually, if you want to age human skin, good old UV-A, aka sunbed, would be my pick.

Justin said...

Eric, that was a side comment. Just mentioning that we are going to make an materials aging cabinet and have been already looking into UV lamps. That made me think of obtaining specific wavelength lamps for stimulating D production after the Vitamin D thing came up. We have already sourced some lamps in the correct wavelength for the project.

Passthecream said...

I bought some luxeonstar 280nm leds earlier in the year to build a mini low voltage portable sterilizer. They're not very powerful but there must be ~310nm leds more easily available in higher power levels.

karl said...

Aerosols have a huge surface area to volume - such droplets can evaporate in seconds - the particle size does matter.

Yes, virion are delicate - but they don't survive long - but do survive long enough - when an infectious person sheds a few million with a cough or sneeze(some goes out the side anyway).. even if 90% of the virus is destroyed - it just doesn't matter.

It is obvious that the masking doesn't cause significant inflections of the death rate - seasonality does - take a look at Sweden's death graph here:

What is key to note is the seasonality - large inflection in the fall as innate immune systems decline. Also - the second hump falls off more rapidly - this is a typical viral graph - things we have known for decades.

If masking was at all effective, we would expect to see such inflections from the policy implementations - but don't. The original bit from the CDC saying public masking is not effective was true then - and still is true.

Masking, light sterilizers are not going to keep you from getting exposed - (R(0)=5 means something) you CAN do things to change what happens WHEN you get exposed - keeping blood sugar normal (postprandial below 110) and vitamin D above 50 can change a nasty flu like experience into something non symptomatic - perhaps just feeling a bit tired for a day. Your innate immune system matters.

The idea that we can stop a virus is hubris - on par with trying to stop it from raining. Pretending that this virus is not like others is not helping the public. The idea that there has been huge breakthroughs in virology in the last year just isn't true - What the CDC knew hasn't changed - only the politicizing of policy is new.

Viruses have evolved to spread - we have evolved to resist them - and we do a pretty good job at it if we don't eat a sickly diet and get enough sun.

Passthecream said...

"(R(0)=5 means something)"

It means that any single thing or combination of things that each weaken transmission by 10% makes an important contribution. I had read 2 though rather than 5. About the same as flu and colds.

If by your reasoning masks make no vast improvement then they also do no vast harm so there's no harm in using them in tight situations if you use the right type and handle them properly.

Passthecream said...

Finally, something that really will make a difference: