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Sunday, 4 July 2021

Qualified Immunity

No, this isn't about the administrative (not legal) doctrine of qualified immunity, it's a science post. More accurately, it's a bit of a general debunking of some dangerous myths currently being promulgated, not least by the horrible Sajid Javid, the new UK Health Secretary who, frankly, is a massive downgrade even from the philandering nepotist Matt Hancock, who resigned last week after being caught in flagrante delicto in what the tabloid clichemeisters would (and did) refer to as a 'steamy clinch' with one of his nepotism-appointed subordinates. Frankly, despite his lack of competence at anything, he still represents a better option than the idiot Randian who now occupies that seat.

So, Javid has issued a policy proclamation. Not via the usual government channels, of course, because this recidivist government doesn't give a flying fuck about protocol and procedure. This policy proclamation has been issued as a written exclusive in the Racist on Sunday. Seems legit.

But anyway, this proclamation is that the best way to protect the nation's health is to ignore all the advice given by genuine experts and let the Delta variant (and others) loose. I want to take a bit of time to talk about just how utterly stupid and irresponsible that is.

Let's start with viruses, antibodies and vaccines. This shouldn't be taken as a detailed dissertation on the topic, just a much-simplified cursory overview.

A virus is like a little machine. It isn't alive, at least under current definitions. We've talked before about the difficulties inherent in defining life, and those difficulties apply here, but there's one characteristic so essential to all our attempts to define life that it's highly unlikely it will ever be excluded; self-reproduction. We define viruses as not alive because they don't have it. They're like the little nanobots in The Day The Earth Stood Still, with some minor operational differences.

Viruses replicate by usurping the replication machinery in living cells. They bind to a cell and secrete genetic material (the precise details of what and how vary from virus to virus, separated into broad classifications) into the cell, at which point the cell starts to churn out copies of the virus, which go on to bind to other cells, and so on. Production of virons is very rapid. 

The virus has several important structures but, for our purposes, the key structure is what's known as the 'spike' protein - the binding site from where the genetic material is secreted from upon binding and, more specifically, the 'antigen' (properly, an antigen is anything that triggers an immune response, but softly softly, and all that), which brings us neatly to antibodies.

Prior to vaccines, your immune system - T-cells , B-cells, etc.,- would produce antibodies, Y-shaped proteins whose sole purpose is to attack foreign genetic material in your body. They're the body's natural defence mechanism against viral infection. For the most part, it's incredibly effective, and gets on with its business and fighting viral infections without you even being aware that it's doing so (often asymptomatically), but now and then something throws it a curveball, and it's all to do with recognition.

Humans have been living with viruses as long as there have been humans and before. In fact, one of the best resources for molecular evidence of evolution is viruses, specifically viruses known as 'endogenous retroviruses', or 'ERVs'. These are essentially strands of viral DNA or RNA that have become embedded in our own genome, and this provides a stunningly good roadmap of evolution because we can track different viruses back to different sources, so they provide more data points for speciation. We can tell whether an ERV insertion happened post- or pre-divergence between closely related species. And, of course, they provide exactly the same nested hierarchies as all the other molecular evidence. Truth, thy name is consilience. Anyway, the antibody binds to the virus at the antigen, and this is the crux of the matter for our purposes. That binding is the whole immunity shooting match. 

As this massively simplified diagram shows, there isn't just one antigen. There are very, very many, almost as many as there are viruses, and they cluster around the spike protein. There's loosely a kind of lock-and-key system that governs the binding. Your immune system will initially throw the kitchen sink at the invaders. It will try every trick in the book to get rid of them. In fact, most of the symptoms you experience with many viral infections is the actions your body is taking to get rid of the 'damned furriners'. Your T and B cells go into overdrive, throwing every kind of antibody at it, figuratively throwing shit at the wall literally to see what sticks. Once it finds a fit, it shifts into production of just the effective antibodies*. At this point, it's all over for the virus bar the shouting. It's important to note that the fit doesn't have to be perfect, it only has to be good enough to prevent binding, and that's where variability arises.

Historically, harking back to Edward Jenner and his foundation of the science of immunology after noting that milkmaids who'd had cowpox obtained immunity to smallpox, vaccines were based on an attenuated or weakened version of the virus it was formulated for. Given the above, it's easy to see how this works. You send in a weakened form of the virus, your immune system attacks it with the kitchen sink, yada yada... 

Vaccines have proven to be very effective, very safe (some caveats here, which I'll come to) and resulted in the 1979 announcement that smallpox had been eradicated. Bear in mind that smallpox had put a sizeable dent in its mission to eradicate the human population of Europe, estimated at twenty percent by Voltaire, writing 200 years earlier.

There is always an element of risk associated with inserting things into the body. That's as true of vaccines as for anything else. Anaphylactic responses are pretty rare, and tend to occur on a sliding scale correlated strongly with other allergies; in patients who have a tendency toward anaphylaxis, in other words. It's also not beyond the realm of possibility that even a massively weakened form of the virus can be fatal, because survivability is a variable in patients.

Anybody who tells you vaccines are entirely safe and without risk is lying to you, but the risks are far outweighed by the benefits, as the millions upon millions of lives that have been saved by vaccines compared to the number of vaccine-driven deaths or injuries testifies quite readily. This is not to minimise such instances, only to give them proper context.

In recent decades, research into a new kind of vaccine has been continuing apace. Much of the detail of how mRNA vaccines work is surprisingly similar to what's gone before, but there's one critical difference. Whereas conventional vaccines used attenuated versions of a live virus, thereby co-opting cells to produce virons, mRNA vaccines work by injecting a specific stretch of messenger RNA into the cell. This mRNA is the 'instructions' for production of a specific protein, the antigen.

So, there are clear advantages here. While reactogenicity for mRNA vaccines is very similar to that of conventional vaccines, there's good reason to think this can be mitigated with further research. More importantly, they're vastly superior in terms of cost and ease of development and production, and provide humoral immunity (immunity to macromolecules in the body's fluids), which conventional vaccines do not. Moreover, there's no virus here, even a weakened one, which means that immunity can be achieved with reduced risk of manifesting symptoms beyond those of the immune response. Remember that viruses cause damage. mRNA vaccines mitigate that completely, rendering them safer than conventional vaccines, and safety will only improve with further research. There is foreign RNA, but it's no different to that of the antigen precursor RNA in the original virus, so the probability that there would be any additional long-term effects is very low, and can safely be considered negligible when set against the benefits in terms of mortality overall.

The other major difference is the reason that the research into mRNA vaccines is decades old and we're only hearing about it in a general clinical setting now, that the hard part is getting the RNA into the cell without a virus to inject the cell, and without the RNA being attacked by the immune system and by RNA-eating enzymes (RNAses) prior to getting it into the cell to do its work. It's a sicky issue, but so is the solution (you might want to hold a groan in abeyance here).

The details vary, but the key is in the protection mechanism. A molecule of fat - a lipid - is given a positive charge. Because RNA (and DNA) is negatively charged, it binds to the lipid, forming a sort of nanoparticle of a pair of 1 lipid and one RNA molecule. When agitated or left to settle under Brownian motion, they clump together, forming a sort of 'circle of wagons' (yes, kids, I'm giving my age away; this is something they used to do a lot in cowboy films) to protect the RNA. Because the overall agglomeration is neutrally charged, the RNases and the immune system pay it no attention. There's an interesting pointer to how the body knows it's being invaded there, but it would take us too far afield. 

Anyhoo, this neutrally charged agglomeration makes contact with the cell. The outside wall of a cell is primarily composed of... lipids. The cell easily absorbs the RNA and gets to work producing the antigens. 

So, that's how all that works. Let's move on and talk about immunity in the population more broadly, because there's a huge amount of misunderstanding out there in publicland with very little offered by way of measure. 

The first thing to look at is what prompted the title of this piece; herd immunity.

There's been an awful lot of bullshit spoken about this, and it's really, incredibly dangerous. In popular parlance, herd immunity seems to have become defined as a method, that of letting the virus run unchecked throughout the population to develop immunity naturally. That's certainly one way to achieve it, and it's been the way we've achieved it in the past, but it has some distinct disadvantages. Before we talk about those, let's talk about what herd immunity means to an epidemiologist or a virologist.

In technical terms, herd immunity isn't a process, it's a status. For various reasons, there are people who can't be vaccinated. We've touched on a couple, those with severe allergic reactions. There are others, though. There are various reasons one might be immunocompromised, for example. Radiation therapy and chemotherapy for cancer, for example, can eradicate the immune system pretty comprehensively while treatment continues. Various diseases such as AIDS and other immune deficiencies, as well as lupus and other autoimmune diseases (autoimmune diseases are, as the name suggests, diseases which cause your immune system to attack your own body) are all contraindicators for vaccines.  

So clearly we can't vaccinate everyone, and of course many of those who can't be vaccinated would also be hugely at risk from a viral infection, even a strongly attenuated version. That's where herd immunity comes in.

A virus needs a route. In technical parlance, these routes are known as 'vectors'. The term means loosely the same here as it does in any area of science or mathematics. Think of it as an arrow, or a path. It's tempting to think of this as the virus coming to the edge of a population and working its way inward, but that's misleading. usually, a virus is already in the midst of a population before it starts to spread, because it's spread person-to-person, even if secondarily via surfaces or pets, etc., so it radiates out from an origin. 

It's really important to note at this point that vaccines DO NOT prevent infection. This is another of those things that I've seen some equivocation on, and that equivocation needs to be stopped, because it's a categorical fact that no vaccine prevents infection. That's not what vaccines do and, if you spend even three seconds thinking about it, it becomes glaringly obvious why; virons don't know you're vaccinated.

OK, that was a bit glib, reminiscent of the sort of hand-wavy dismissals normally considered unbecoming of a sceptic, but there is a serious point in there. Virons get transferred from host to host without any sort of cognitive work being done. If you have one viron in your body, you're infected. If you have one viron, the likelihood is small that you won't have at least one cell replicating virons. What the vaccine does is to give you a head start in fighting the attack. You can still be infected and have the virus multiplying inside you, all while having no idea, and while thinking that you're covered because you're vaccinated. 

The effectiveness of immunity in reducing transmission is a complex issue, manifesting in two main ways. The first is that, because of those lovely antibodies drastically reducing the amount of time you can carry the live virus, it reduces the amount of time you're infectious. The second is that, in a partially vaccinated population, transmission in absolute numbers increases for various reasons, though this tends to level off and subsequently decline as immunity increase in the population overall. 

This is why those in the know still advocate wearing masks, washing hands frequently, keep safe distance from people outside your bubble, etc. It's a team effort, not just involving all of us, but also involving all these measures working in concert. Going out without a mask just because some of us have been vaccinated is like starting a world cup final with only your strikers on the pitch against a full side and leaving the rest of the team on the bench.

There's another factor in this, even more critical in strategic terms, and it's worth looking at it properly, because exposing it is instructive in scientific terms and in terms of how shallow the thinking is behind the desks of those making decisions at the moment, largely against all scientific advice. 

Herd immunity isn't some easy target. It's very much a moving feast, the reasons for which, while complex, are rooted in very basic and well-understood evolutionary principles that you don't need to be a virologist to understand, at least in principle. The current estimate for effective herd immunity for SARS-CoV-2 is somewhere between 80 and 90 percent. It's too early to tell if that will be revised much, but that's not untypical. That figure can go up, though, and that's a problem.

Organisms evolve. In particular, the offspring of organisms are slightly different to their parents because of processes involving transcription errors during replication. This is as true of viruses as it is of living things. In fact, evolving is something that viruses are extremely good at. There is, in fact, extremely strong correlation between rate of evolution and length of genome. The influenza A virus, for example, has a genome of around 13,500 bases, and it evolves at such a rate as to require updated vaccines approximately every two years, give or take. SARS-CoV-2 has a genome approximately double that, so we can expect commensurate evolvability rates. Note, though, that this is a strong correlation, which doesn't mean there's a useful metric or we can make solid predictions only that we have good baselines for guesstimating rates.

It's a deeply important point to remember that, when I talk about an evolution rate requiring updated vaccine every two years, that rate of evolution isn't really rooted in time. It's not the case that x evolves at y rate in time. It's the case that x evolves at y rate per z replication. For example, if I toss a coin and try to obtain ten heads in a row at a probability of  1/1024, each series taking twenty seconds, it will take approximate six days. In fact, it can happen on any one of the attempts in that many trials (or even more, but it will average out over more and more trials to 1/1024). More importantly, though, if I have 1024 people all tossing coins at the same time, it becomes statistically approaching certainty that somebody will do it on the first attempt.

In fact, it's a given that, when fully infected, somebody suffering from a given virus is almost carrying more than one strain, but one will be sufficiently dominant to massively outnumber any variants. However, if a new variant arises that has an advantage, such as being able to replicate slightly faster, it will tend to dominate. Remember, though, that evolution is itself evolvable. So any variant that can replicate faster will not only be better represented in future population resamplings, the trait itself will evolve over subsequent generations.

The same is true of vaccine resistance. A variant that has better resistance to vaccines will give rise to variants that have even better resistance, and so on. Any survivability (known as 'fitness' in the jargon; this is the proper definition of fitness as used in evolutionary theory) gradient will increase evolvability, in other words. Every new infection increases the probability of the emergence of a variant sufficiently vaccine-resistant either to only be slowed down a bit or to rip through the world as a brand new pandemic and we're off to the lockdown races again.

There's one more important evolutionary factor that I haven't covered, and it's a biggie. It's all to do with how this virus arose in the first place, and what some of that means.

As far as we can tell, the virus originated in wild bats in China. The notion that it's a human engineered virus is arse-water, provably, and this has been known since the mapping of the viral genome in march 2020. There are myths about 'four negatively charged acid bases', and that sort of thing, but they're all as demonstrably false as this claim, whose falsity is trivial to demonstrate with examples of where such a quadruplet occurs (HIV, SARS, MERS... and the hits keep on coming).

The exact aetiology isn't known, because it doesn't look like transmission between bat and human was direct. It almost certainly arrived via another species, based on the protein binding site for the spike protein, the bit of the virus that does the injecting. The best guess so far is pangolins in a market, though the market in question - as with markets all over the world - was stocked with many live animals. It is clear, however, that all the available evidence points to a natural origin, despite what the conspiracy theorists extract from the rectal cavities. That's not to rule out a lab origin completely, but there's simply no good reason to go there as yet.

The point I'm wending toward is that one of the reasons that viruses can hop between species like this is because of something that's almost entirely peculiar to viruses; lateral gene transfer.

In the vast majority of cases, gene transfer occurs via reproduction. In the case of viruses, however, they can cross 'species' boundaries. I use the scare quotes advisedly there because, although we use the same taxonomic nomenclature and hierarchies, the terms don't really mean the same. Regulars will recall the care we had to take when defining a species in the evolution megapost, and how we had to be careful not to apply our species concept too rigidly or it would lead to absurdities like classifying Ebola virus as human. Some of that was to do with retroviral insertions into the genome, but some of it was also about the fact that viruses can share genes. This has consequences, one of which is the ability to inherit the genes coding for spike proteins and other structures that are effective in other living species. That's how a virus originating in bats can transfer to pangolins, pick up the genes for the spike protein, get transferred on to humans and good morning, pandemic.

This also has some interesting consequences for us when dealing with how long the virus is in the population before we get some sort of handle on it. It's easy to think of any given virus in isolation but, as we've learned so often, the world doesn't satisfy our need to put things in boxes, and it's rarely that simple. It's extremely common to have multiple viruses at once, and lateral gene transfer impacts evolvability in a big way, by conferring survivability in some form, whether by replication rate, survivability in air outside solution, survivability on surfaces for longer periods, higher rates of virulence or mortality, increased vaccine-resistance or any of a whole realm of potential advantages. And remember, every survival advantage for the virus, every potential new variant, every new infection, increases the probability that every bit of good work we've done in containing the virus until vaccine rollout can be undone, leaving us to start again at square three. Not square one, because at least we have the preceding research now, and we didn't have that when SARS-CoV-2 first hit.

Now, there's one thing we haven't covered yet, and it's where the rubber is really going to meet the road; young people.

There's a lot of confusion about whether young people should be vaccinated immediately. In fact, the problem is extremely simple, but the solution is a bit more complex. Worse, the misinformation has made the problem seem more complex and the solution simpler. For a change, I'm not even going to look at the misinformation to debunk it (other than the silly 'natural' notion of herd immunity), I'm just going to lay out the problem and what the solutions might look like.

We've looked hard here at transmission rates, evolvability, survivability gradients, etc., and these are all important. The reason they're important goes back to that moving feast of herd immunity. Every one of those factors increases All of the things we've looked at here are factors that impact how long the virus runs uncontrolled through portions of the world population, and that's all important. There is an element of triage, though, and that matters.

At the moment, supply of vaccines is the critical factor. With a world population careening toward 8 billion, we're looking at getting something like 14 billion doses of vaccine distributed worldwide. Now, it would be easy to think that we should just dose up the children and have done with it, but we have to take the rest of the population into account because, as we've seen, any unchecked transmission massively increases the risk of new, entirely vaccine-resistant variants, or even entirely new strains via lateral gene transfer. The effects of this will be indistinguishable from having done nothing, to a first approximation, so careful triage is in order.

There is another confounding factor to account for, and that's something that's increasingly coming to be known as 'long covid'. Viral infections do a lot of damage to your cells and tissues, and the after effects of this particular virus seem to be particularly pernicious, Scarring from pneumonic inflammation can last a long time or even permanently, causing reduced respiratory function, and there are muscular and joint pains and other debilitating symptoms. Moreover, there's now increasing evidence for viral neurotropism as a result of COVID, resulting in measurable reduction in grey matter. These studies have only been done for adults so far, but the implications for developing brains are a cause for very serious concern, and shouldn't be discounted, especially when other strategic failures are looming.

In the UK at the moment, there are at least three variants abroad in the population. We have the parent, or alpha, the delta and the lambda variants. The delta variant is rapidly becoming dominant, with reports of between fifty and ninety percent of all new cases being delta. The delta variant is about ten to twenty percent more vaccine resistant than the alpha. Recall that any survivability gradient increases evolvability; that is to say, each survivability differential in the population increases the rate of evolution. Between the three (known) extant variations in the UK population, that makes for twelve distinct survivability differentials, and not always in isolation from each other, which means a continually increasing rate of evolution. A full-on evolutionary arms race against immunity.

So if we send kids back to school without vaccination, we're almost certainly bringing the delta variant into contact with people whose vaccination is only 90% effective against alpha and approximately 80% effective against delta (these aren't exact numbers, just demonstrations of concept). And what happens when you bring a variant that has some vaccine resistance into a body with antibodies? You end up with a much higher chance statistically of a fully resistant variant.

There's a deeply important point that connects all of this together. We've looked closely at all the factors that can increase the overall impact on the population in terms of mortality, but there's one evolvable trait that we haven't looked at, and which isn't being looked at in any sense in the public sphere, despite it again being a very basic fact about evolution; infection fatality rate. Yes, it can evolve to be more deadly in and of itself. This should actually be obvious to us, since we have different strains and variants of the flu virus with different infection fatality rates. It's not something I'm aware of any data on as yet, and all current variants seem to have a similar IFR profile, but that can change and, remember, if that change confers any kind of fitness gradient, we have a new race on our hands, and a much, much deadlier one, with all the challenges we've already faced ratcheted up by an exponent. I'm being careful not to be a doomsayer here, and I don't want anybody to think I think this inevitable, but the probability of a more deadly variant or strain is increased by orders of magnitude‡ the longer and more widespread the virus is allowed to run, even without all the gradients forcing every extant variant to evolve faster.

Before I wrap up, I just want to expend a couple of words on achieving herd immunity through purely natural means. What it entails, then, is letting the virus rip through the population unchecked. This will, of course, result in the full force of the virus being meted on the planet's population. We'll achieve herd immunity in pretty short order, but the herd will be considerably smaller. And, of course, that's without the survivability differential we've created by vaccinating some of the population. Any such differential, as we've seen, increases rates of evolution, because competition becomes a factor. Allowing the virus to run rampant is always a bad idea if we can mitigate it. Allowing it to run rampant in a partially vaccinated population is stupid. 

Ultimately, these aren't straightforward, one-dimensional problems, and the solution is complex. Certainly, there are other things not being done for schools. A big factor is improving ventilation and air purification. Cleaning pathogens out of the air is highly effective, especially when combined with other things, like screens and masks, and regular handwashing, and not touching your face or mask too much.

What this post has been about then, really, is about how this is a complex problem that doesn't lend itself well to soundbite solutions. It's a post about who you should be listening to, and who's qualified to talk about immunity (SWIDT?) I absolutely don't think I'm the one to be talking about it, other than having a knack, I'm told, for simplifying such things without being misleading. I've certainly gotten some things wrong here, as I've favoured speed over my usual diligence because this problem is becoming more and more urgent, but not in any way sufficiently impactful to significantly alter the over-riding points here.

Listen to the experts. Look at the advice that's being given to the fuckwit in the health secretary's chair, not what's dribbling out of both sides of his mouth. I'll provide some unimpeachable sources for context.

I also highly recommend going and watching all Potholer54's videos on the virus. Peter Hadfield remains, for me, the gold standard of science journalism, with an outstanding research ethic and, more importantly, not only a willingness to be wrong but a love for it, because we always learn more from being wrong, as long as we're willing to learn. As I was going to grab a link, I noticed that he's just now posted a new video, so I'll pop that in at the bottom. I haven't watched it yet, but it appears t be another debunking of the lab leak/engineered theories or something like that. It will be a treat either way, because he always is.

I really do get that it feels like you're really being pushed around, and that being forced into something feels like something that should be resisted with every fibre. I absolutely agree that a government has no moral right to imprison you, or to impose restrictions on what you can wear and where you can go, and so on. I also recognise that people can be quite dumb about things and, especially because of the amount of misinformation on every single topic no matter how inconsequential, people will simply not do the things that are necessary to get on top of the virus. Your freedoms are important to me as well, but the value of anything is tempered by its cost.

You aren't responsible for the well-being of others in any rigid moral sense. You are responsible, however, for the impact of your behaviour on others. I mean, you do you, always, but it seems to me that, if I can mitigate the potential for my transmitting a virus to somebody that could kill them by suffering a few inconveniences such as the team of precautions already discussed and, it doesn't seem too much of a hardship, especially since I only have to continue doing this until we're approaching herd immunity, the state of the population that, for each person that's immunocompromised, it has to go through so many layers of immune population to ge to them that it's functionally impossible. And I hope this makes it clear why the strategies recommended by scientists aren't aimed only at getting out as quickly as possible, but also trying to ensure that we only have to do it once, because every delay exposes all of us to more danger, as we've seen only too well by the increases in deaths directly attributable to failure to act. Think of it as taking one for the team.


Edited to add: 06/07 I see news about the Lambda variant starting to gain traction, and rightly so. While it appears to be as susceptible to vaccines as the Alpha, it has some features that might make a bit of a difference, because the novel mutations are in the spike proteins, specifically in the binding domain. This has the probable effect of increasing transmissibility but, because of the stochastic nature of evolution, it opens up a whole area of phase space for the virus to move into, because that binding domain is, as we've noted, the whole immunity shooting match.

Critical update 10/07: New study by Tea et al in breakthrough infections strongly suggesting reduced immunoreactivity and neutralisation potency against variants in patients re-infected after having suffered in the first wave. This puts considerable doubt in the efficacy of the government's strategy and further undermines the case for reducing restrictions.

Critical update 15/07: New study from China suggests that Delta not only escapes conferred immunity from Alpha, but also replicates initially in the nasal tract much more quickly, which is one of the reasons that it's dominating everywhere. This is significant, because a faster replication rate is another fitness gradient in the same population, meaning that there are now two crystal clear fitness gradients in this single variant alone, both of which are driving clearly in the direction of vaccine escape. Depending on how completely vaccine escape occurs, this can lead to either a horrible endemic (permanently embedded in the world population) disease with long-term effects or the IFR can increase again. 

Also worth noting that the vast majority of new infections are 20s, 30s and 40s, but admissions of children are increasing rapidly.

Critical update 24/07: Extremely strong evidence now emerging of longer-term cognitive effects of COVID. BBC's flagship pop-science documentary series, Horizon, has been running an experiment called the "Great British Intelligence Test". As a result, they have testing data on eighty-thousand subjects. They conducted some follow-up testing, and there was a clear link between having had COVID and a detectable difference in cognitive function, with a solid correlation between severity of symptoms and loss of cognitive function. These differences seem persistent even long after all other symptoms have abated. See the paper published in The Lancet below. ONS estimates about 643 long COVID sufferers in the UK alone. 

Critical update II 24/07: A new study showing brain inflammation and the production of Lewy bodies in macaques. Lewy bodies are protein inclusions in the brain, strongly associated with several types of dementia, and having a particularly strong association with Parkinson's disease. It's important to note that there was an abnormally high incidence of Parkinson's following the Spanish Flu pandemic of 1918.

Critical update 28/07: Evidence emerging of increased risk of myocarditis (which includes pericarditis and myopericarditis). A hump in the data from the history of mRNA vaccine research shows a small risk of myocarditis in people under 20 years old, which is the main motivation for withholding the vaccine from young people. This new study shows that the same risk exists from infection with the virus at a rate six times that of the vaccine. This, if confirmed (the paper is a pre-print), is the loadbearing stick in the Jenga tower of the conclusion that we shouldn't vaccinate children and young people. To withhold the vaccine in light of this would be to knowingly subject children to risk of death with no good reason. 

Update 29/07: New BMJ-published study showing ocular defects associated with long COVID.

Update 30/07: This is a pretty big one, with potential implications for almost every aspect of COVID. New evidence emerging that T-cell immune response is running to autoimmune - autoimmune is when your immune system attacks your own body, remember. This could well mean that most of the symptoms of those who get really sick from the virus are actually immune-response symptoms. As I mentioned above, it's often the case that many of your symptoms are actually the immune response, but this is one step further. This specific T-cell response is correlated with age, with stronger responses leading to more sever symptoms. It also opens up several doors in terms of our response. For example, we could seek interventions that suppress or attenuate T-cell response to lessen symptoms. Recall the strong correlation between severity of symptoms and severity of long COVID, for example. See the paper in Nature below. 

Update 03/09: New study showing reduction in kidney function in post-acute COVID (long COVID). See paper from the Journal of the American Society of Nephrology below.

BMJ Letter to Sajid Javid detailing recommend precautions for schools, among other things.

Johnson’s reopening is a potential recipe for disaster - Letter from a group of clinical virologists expressing their dismay at the government's proposal to remove all restrictions on the 19th.

Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study - Osmanov et al European Respiratory Journal 2021.

SARS-CoV-2 Lambda Variant Remains Susceptible to Neutralization by mRNA Vaccine-elicited Antibodies and Convalescent Serum Tada et al CSHL 2021

Brain imaging before and after COVID-19 in UK Biobank Douaud et al 2021 - a brain imaging study on patients before and after COVID, showing signs of reduced grey matter due to viral neurotropism. No such similar study exists for children, and this has serious implications on developing brains and is a major cause for concern in long COVID.

Vaccine Breakthrough Infections with SARS-CoV-2 Variants - Hacisuleyman et al NEJM 2021: Post-vaccination infection with multiple variants.

Trish Greenhalgh: Freedom Day, but at what cost? - professor of primary care health sciences, University of Oxford, UK, writing about some of what I've covered here with more sources.

Physical phenotype of blood cells is altered in COVID-19 - Kubánková et al 2020 -  a study in changes in the blood cells as a result of COVID as potential explanation for long COVID symptoms.

SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants - Tea et al 2021. Study on patients re-infected after having been infected in the first wave, showing lack of conferred immunity against variants.

Efficacy of face masks, neck gaiters and face shields for reducing the expulsion of simulated cough-generated aerosols - Lindsley et al 2021. Metastudy on efficacy of different masks and face coverings in reducing spread.

Ten scientific reasons in support of airborne transmission of SARS-CoV-2 - Greenhalgh et al 2021. Evidence that SARS-CoV-2 is airborne.

Viral infection and transmission in a large well-traced outbreak caused by the Delta SARS-CoV-2 variant - Li et al 2021 - new study from China on virulence of Delta.

Cognitive deficits in people who have recovered from COVID-19- Hampshire et al 2021 - New study from the BBC's Great British Intelligence Test showing evidence of loss of cognitive function in COVID sufferers, published in The Lancet.

SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques - Philippens et al 2021 - Study on COVID in macaques. See critical update II 24/07

Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis - Singer et al 2021. Study on myocarditis risk in COVID patients under 20. See critical update 28/07

Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID - Biturgen et al 2021. Small study showing ocular defects associated with long COVID.

SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection - Cohen et al 2021. Study showing correlation between age and t-cell response.

Kidney Outcomes in Long COVID - Bowe et al 2021. Large cohort study in veterans tracking for unidentified symptoms of post-acute COVID showing reduction in kidney function. 

Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents - study of Pfizer vaccine in adolescents, linked here to counter a claim that this vaccine has had many adverse reactions.


Additional 07.07 after some asinine comments on social media:

Thought I should pop something in here for the anti-maskers and those who suggest that masks are ineffective at preventing spread. Of course, when somebody asks for evidence that masks prevent spread, what they're really after is a study that directly compares infection rates in double-blind, controlled environment. No such study will ever be done for the simple reason that the experimental design necessary woudl fail the most basic principles of ethics.

However, I can shed some light here, because this isn't a medical question, it's a question of physics and integers, and physics can show quite easily an undeniably the effectiveness of masks in reducing transmission.

Integers first: Fewer virons suspended in the air - whether airborne or aerosolised† - means a lower probability of infection. Entirely uncontroversial. A simple function of how probabilities work. Fewer components = lower probability. Direct correlation. 

If you reduce the escape velocity, you reduce the range. Super simple. If you throw it less hard, it doesn't go as far. We don't even need Newton for that one, surely. I mean,  can draw a diagram, but...

So, imagine if we had something that we could put over an exit that effectively both reduced the quantity and range of virons being expelled from the orifice. That sounds like something we can do a proper physics experiment on...
  
Which mask works best? We filmed people coughing and sneezing to find out - Non-rigorous study at UNSW with some good advice on masks, including how to make your own. 

Case closed.

Has Evolution Been Proven? A comprehensive guide to evolution and the mechanisms behind biodiversity.
The Unbearable Shiteness of Beings More on vaccines and immunology.
Testing Times A quick and dirty debunk of the silly notion that PCR can't test for COVID.


* The way I've presented this is slightly misleading. In particular, it looks like I'm saying that the key to beating the virus is somehow already there in the kitchen sink, which is not always the case. There are also white cells known as 'leukocytes' which play a primary role in all of the body's immune response - not just against viruses but all foreign invaders. They're divided into categories based on what their role is in the immune system. Of interest to us are the lymphocytes, whose role in a viral infection is to try to break bit of the virus off and present them to the immune system searching for a strategy of attack. This all sounds very thoughtful, but there's no thought involved, of course, just chemistry. In any event, once a strategy has been identified, production goes into overdrive and we're off again.


† These are not the same thing, despite the usage by scientists speaking in public. An aerosolised virus is virons suspended in fluid droplets or mist, usually mucus and saliva. An airborne virus is one that has evolved tiny hairs that increase surface area and allow the virons to stay suspended in dry air for longer. The reason for the combined usage by medical scientists talking in the media is because people are confused enough without having to explain the difference between these two, especially when the implications are functionally identical. ETA 12/07: We can now define this virus as actually airborne rather than merely aerosolised. This is impactful in terms of strategy, because we have to see the air we breathe as containing virons. Paper added in citations.

‡ Regulars will be grimacing at this, because it isn't actually possible to increase probability by orders of magnitude, given that a probability must be between zero and one.

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