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Just one month ago, the idea that most people aren’t susceptible to Covid-19 — perhaps the overwhelming majority — was considered dangerous denialism. It was startling when Nobel-prize-winning scientist Michael Levitt argued in UnHerd at the start of May that the growth curves of the disease were never truly exponential, suggesting that some sort of “prior immunity” must be kicking in very early.
Today, though, the presence of some level of prior resistance and immunity to Covid-19 is fast becoming accepted scientific fact. Results have just been published of a study suggesting that 40%-60% of people who have not been exposed to coronavirus have resistance at the T-cell level from other similar coronaviruses like the common cold.
Now, from the unlikely source of a prominent member of the “Independent SAGE committee”, the group set up by Sir David King to challenge government scientific advice and accused by some of being populated with Left-wing activists, comes a claim that the true portion of people who are not even susceptible to Covid-19 may be as high as 80%.
Professor Karl Friston, like Michael Levitt, is a statistician not a virologist; his expertise is in understanding complex and dynamic biological processes by representing them in mathematical models. Within the neuroscience field he was ranked by Science magazine as the most influential in the world, having invented the now standard “statistical parametric mapping” technique for understanding brain imaging — and for the past months he has been applying his particular method of Bayesian analysis, which he calls “dynamic causal modelling”, to the available Covid-19 data.
Friston referred to some kind of “immunological dark matter” as the only plausible explanation for the huge disparity in results between countries in an interview with the Guardian last weekend. The eye-catching phrase attracted a lot of attention on social media, with some commentators keen to dismiss it as rubbish, but he meant it in a quite precise way: like dark matter, the undetectable substance that makes up approximately 85% of the universe, it is provably there by its effects. We just don’t know anything about it.
His models suggest that the stark difference between outcomes in the UK and Germany, for example, is not primarily an effect of different government actions (such as better testing and earlier lockdowns) but is better explained by intrinsic differences between the populations that make the “susceptible population” in Germany — the group that is vulnerable to Covid-19 — much smaller than in the UK.
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SubscribeAs someone over the age of 65 I have found the whole panic reaction to Covid-19 shocking. We take health risks all the time and in particularly with the brother of Covid-19, the annual winter flu. I have opted not to have the flu vaccine because I feel it is not necessary for me personally, given my track record of avoiding and fighting such day to day ills. Thus I would be happier to have followed the UK government’s initial response to shield the vulnerable. This would have been for the greater good of our populations in health, economic, psychological and spiritual terms. Every year thousands die from flu, other long term conditions and other long term conditions complicated with flu. 2015 was a year that saw 50,000 here in the UK yet there was no panic just the annual winter crisis for the NHS. This revelation cements my thinking on this issue. I am willing to take the risk to shield the majority, in particular the younger generations from the unintended consequences we all now face for a long time to come.
I agree with you. Is a life without risk really a life worth living?
Thank you for that, a most stimulating essay/interview.
However it’s a bit late now, is it not? The die has been cast and absolutely nothing can now prevent the appalling havoc of both economic and employment destruction that is to come.
Future generations will marvel at this catastrophe, and think themselves accursed by our stupidity, and who can blame them?
Possibly, but can you imagine the result if the government were to say they were wrong all along, the science was wrong, and we should never have locked down? The reason for the 14 day quarantine is solely because the focus groups said they wanted it.
Agreed.
It would have taken a far more courageous group of politicians than we have in either major party to have faced down the public panic at the start of the outbreak. I’m not defending them but it’s hard to see what else they could have done except lock down, given the pressure from the public and, especially, the media.
Let’s say the lockdown made no difference, once deaths had started hitting hundreds a day the government would have been faced with a situation where their scientific advisors were telling them they were wrong and every single death was being blamed on their stubbornness – I don’t think the government would have survived.
The one fact we know is that people were terrified, it may well be that this was a gross over reaction – but we couldn’t really be sure of this at the time. We, as a population, panicked and demanded panic measures – and that’s what we got. Though the wartime analogies are often overdrawn, it’s all very similar to what happens at the start of a war, especially as we were working to a plan that bore little resemblance to the facts on the ground. Rather like the French relying on the Maginot line.
It would be nice to say that we won’t make the same mistakes next time round, but it’s more likely thatwe’ll simply make different mistakes
The main difference being that neither we or any other country will be able to afford a subsequent lockdown-no matter how terrified the population is-you might have a problem persuading them that they can’t have an extended holiday again but i suspect so many will be unemployed that the message has got through.
No, some people were terrified. And they were made terrified firstly by the irresponsibility of the Press, reporting worst case scenarios as established scientific fact, and latterly by the government following its own propaganda narrative, for reasons so far unknown.
Spot on, hysterical screaming self publicists on morning “news” shows
Quite! The government and its press lackies, chiefly the BBC peddled this hysterical rhetoric to frighten us into submission and that the NHS is the nearest thing we have to a state religion and the merest utterance of dissent or minor criticism is typically met with howls of derision.
The most worrying thing for me is the prospect of there being some agenda or putsch behind this. Economies are being wrecked, perhaps irrevocably and people with other life limiting or chronic conditions could not access treatment due to Covid-19 have died, have worsened and will likely continue to do so as a result.
What kind of NHS will we have when were all on benefits and not paying into HMRC coffers?
Don’t forget that the US press had political reasons as well to magnify the threat.
People were/are terrified but why? Have they completely lost all their critical faculties? The Great Satan-the Media must take some of the
responsibly, but really in the 21st century, is this the best we can do?
I liked your analogy about war. We do traditionally get off to a poor start in many of our numerous wars. Both WWI &II, the Boer War, Zulu War, SevenYears War, even the’45 Jacobite Insurrection, to name but a few, so you might have thought we were inured to adversity. Not a bit of, now we have been reduced to mob of panic stricken bedwetters with trembling upper lips. Perhaps the root of this malady is somewhere in the educational field. For eons now, the State system has taught its victims to despise everything about great British values, Empire, courage, moral fibre etc; Yet replaced it with nothing more than vacuous platitudes. Now we are reaping what ‘they have’ sown.
I tend to agree with you that given the spinelessness of current politicians it would have been impossible to avoid the Lockdown. However had we had someone of the calibre of say William Pitt, Palmerston or even Gladstone, they would have withstood this tsunami of funk.
Finally, with an eighty seat majority, only a later day Guy Fawkes could topple this Government.
It’s been global hysteria
True, but focus group sentiment can turn on a sixpence. Just report some emotionally laden story of tragedy related to lockdown….preferably involving children. Enough of that and the press will ‘reverse ferret’ – and the population with them – sooner than you can say “it’s the science”.
They’ve said it in Norway, and Chicken Licken is still waiting for the sky to fall.
If Friston (and Levitt) are broadly right, even self-serving governments will soon start to dig themselves out of the pit that they have made for themselves. The latest idiocy, at time of writing, being the proposal for 14 day quarantine of incoming travelers. Even conventional epidemiological analysis says this is pointless, but Friston’s analysis multiplies its pointlessness by the reciprocal of the dark matter constant.
Plus the now mandatory wearing of face masks on public transport what a joke!
Fortunately, I still possess a NATO Gas Mask, designed for ‘full on’ NBC Warfare. I’m looking forward to wearing it on the Bus.
Yes, this rapidly turning into the greatest shambles since Dunkirk.
Freddie doesn’t have to apologize for taking a break. One learns more from his interviews on COVID-19 than any other source. Freddie writes that the “‘effective susceptible population’ was never 100%, and was at most 50% and probably more like only 20% of the population.” That’s a pretty big range, but even if you take its lower bound as being accurate, it surely undermines a lot of the lockdown procedures introduced in the UK and other Western countries and the world-will-never-be-the-same-again rhetoric we are fed ad nauseam. As Friston says, there is way more work to be done on the subject. Let’s hope it gets done by fearless researchers willing to follow the data wherever it takes them. We should have data on infections and deaths cross-classified by race (something we don’t have in Canada, now) and by country of origin, even at the risk that their examination will be exploited by social justice warriors eager to turn the discussion to systemic racism based on ludicrously small datasets.
Sadly, Freddy, I think your final paragraph is wrong. My observation is that people are not becoming less afraid, note the number of parents still reluctant to send their invulnerable children to school. Those who are cavalier about the risks – see street parties in London recently or large-scale demonstrations – are from communities where many members have ignored the social distancing rules from the outset.
Please don’t torpedo the recovery!
Surely it is apparent that this whole ‘thing’ has been the greatest confidence trick since the Resurrection?
Whether it’s been a confidence trick or not, nothing that he said is wrong.
Really? The anarchic picture of ‘wicked’ Londoners is surely an exaggeration? Also in my bucolic bit of this sceptred isle most of the parents have been only too anxious to despatch their ‘invulnerable’ offspring back to school, and should applauded for doing so, don’t you think?
Perhaps I have a different ‘periscope’ to Undersub?
the greatest confidence trick since the ResurrectionA heretic! Kill!
Anyway, could you perhaps explain your reasoning or evidence here? Who conned whom, how, for what purpose? The oldest extant reports suggest that the principal actor JC cleared off from the scene due to a price on his head, and was never heard of again.
(I can indeed think of a more credible such thesis in respect of a more recent Arabian gentleman.)
The accepted facts seem to be that Pontius Pilate was obviously a bit of
a pseudo liberal ‘cuddly bunny’ who gave JC a very humane Friday afternoon Crucifixion. A standard Crucifixion meant writhing on the Cross for perhaps as long as three days. The Friday afternoon job,
meant only about three hours, so as to conform with Jewish Religious practice, which required you to be dead by sunset. Hence the spear in the side and broken legs as administered by Centurion X etc.
No man could survive this, so I am intrigued to hear your news that JC “cleared off with a price on his head”.
It boils down to that weird word faith, belief in the unbelievable as the Ancients would say.
Personally I believe the Roman knew what we’re doing, after all they had had enough practice, and that survival was impossible. Others are obviously entitled to think differently in any free society.
The real (to evil atheists at least) truth was revealed to me on a Tablet of Stone handed to me by a certain Christopher Brand (r.i.p.). The soldiers in the duskness of the Garden of Gethsemane grabbed the wrong person, and consequently J.C was still free. Judas subsequently hanged himself due to his guilt for betraying “an innocent man”. None of JC’s group were close enough to the crucified victim to positively non-recognise him. Thus Xtianity began with a NON-hoax. The witnesses to the resurrection really did see him.
He was last seen heading off along the Emmaus Road before anyone else could catch on. Thus unlike faiths, Christianity began with believers actually telling the truth. Which I suspect is part of why it has been the most powerful force in history (and still is 2000 yrs on). A certain other famous faith is famously dependent on having to scare people into declaring their belief in it….couldn’t possibly have got started like that could it? (Hint, see verses 2:8-2:20.).
How very interesting! It sounds like the “Life of Brian” wasn’t far out then?
I think you will find there are quite a few other contenders for the prize of “most powerful force in history”.
Your criticism of the “other famous faith” is valid, however the later followers of JC were very keen on immolating others to ‘save their souls’. I gather at one stage it became a highly erotic spectator sport in Germany for example.
In which ‘book’ are those verses you refer to at the end of your epistle?
Unless the JC story is just a fiction. Written by some cranks (or entrepreneurs) who could dream up a future for themselves by selling a dream to common folk living in filth and poverty under a corrupt overlord society.
Something like that certainly happened, the question is whether it was Divine or Man made?
Robin Clarke’s account on this thread is interesting, although obviously I prefer the “Life of Brian” version, along with Zosimus, Gibbon, AHM Jones & Co.
People will slowly become less afraid if they see others doing normal things and noticing that there are no bodies piling up on the streets as a result.
Now, don’t say I’m wrong please. I’m banking on this otherwise we truly are doomed.
Two psychology problems. Firstly, being an anti-distancing heretic looks “bad”, so very few of us defy the rules. Secondly, when a person obeys the ideology they tend to end up believing it.
Two points that, sadly, seem to be absolutely true.
I would love this to be true but I fear the press and govt telling us on a day to day basis how many deaths not this % of the population have died and % has not. May just have made it more transparent. Press are having a field day with sensational views a level of attention they have not had the pleasure of for years
Well, the BLM mob are doing the experiment for us. Tens of thousands of demonstrators jostling together, rushing to hug BAME people in solidarity.
Will they get a spike of infections? If not, then lockdown is over!
Poor analysis. Open air with masks, while more dangerous than one’s apartment, is orders of magnitude LESS dangerous than office environments, sporting arenas, and unmasked pubs and restaurants.
The rush to “re-open America” shows states leading the race have led the numbers of infected, as well.
“2017 YouGov shows Ukip members be typically less educated and heavily concentrated in the lowest income brackets.”————-If by less well educated you mean they don’t have a degree, then you’re probably right. Most people before the late 1990s didn’t go to university. They went out to work at 15 or 16, often in apprenticeships which gave them an education, or they got life experience. That doesn’t make them thick or uneducated.
I’m not sure the author is suggesting that Kippers etc are necessarily thick. Just that they often have a “lower” level of education which leads to different life experiences and political priorities and preferences. Hence the alt-left and alt-right are two cheeks of the same left behind arse – So to speak…
Fascinating take. However, stateside there are lots of jobs in STEM and tech fields, that go unfilled in the USA, which is why so many hard-working and tech minded immigrants from India, China, Russia and slavic countries are in demand to fill them. About 3 million jobs go unfilled annually. Too many American students choose to major in topics that will not get them anywhere, including the ‘Studies’ (Ethnic, Feminist, etc) and Sociology. Moreover, It’s been said that it’s the Sociology Departments in universities that have invented such terms as ‘white privilege’ and ‘systemic racism’ which stoke the anger we are seeing. It’s their students who are not finding jobs and are also indoctrinated to be angry. Seems to me that it’s the (1) failure of the self-interested educational system that is the crux of the problem and (2) parent who neglect to guide their kids.
It’s tragic that vocational education isn’t promoted more. Not every kid is able or wants to sit at a desk all day.
If immunological dark matter was established uncontroversial fact, and we could establish which populations were protected by it, in November 2019 then the advice to government would have been different. As it was, the unkowns were unknown, and there was no option but to implement standard infection control measures if the primary goal was to save the lives of the susceptible. Government action may indeed prove to be irrelevant in certain countries, but this does not let governments off the hook. Ignoring the best available evidence for ideological reasons, even if later that evidence is wrong or partial, is a risky basis for policy making. One might as well ditch all scientific advice due to its degree of uncertainty in many fields. Or perhaps a more honest approach is for a Minister to say “you know what? Science indicates we should do x but we are not going to do so because we have other goals and the science could turn out to be wrong.”
You mean like Brexit?
Certainly interesting and intuitively in line with what we understand of existing coronaviruses. E.g. if anyone has ever worked in a multi occupational air conditioned office they will very likely have encountered the “heroic” person who comes to work with a visible (audible / tactile) cold. Does everyone in the building become “infected”? The majority will come into contact with the virus and some display more symptoms than others. It is not a binary, have it / don’t have it.
Clearly this coronavirus is novel and patently more deadly in increasingly understood demographics. Therefore, caution (panic, call it whatever) was well exercised. Knowledge is power and increasingly we understand more about this virus.
If anything good comes of this hopefully it will be preventing John in accounts from coming into the office and “battling on manfully”. Hate John. Don’t be John
Scientific advisors can only go by what they know at a particular time. Anyway the Swedish scientific advisor himself says he was wrong and too many people died because of the lax measures he advised.
*sigh* He was not talking about the general measures that Sweden used; he didn’t and dosn’t renounce the lack of lockdown. He simply said that there were lessons to learn, particularly in the care homes and testing.
yup. As ever it is not a simple right / wrong exercise as Mike references. Things went wrong in care homes in Sweden, lack of preparation and the nature of care homes in Sweden. Other things will have gone right – schools remaining open a very apparent example
When you are asked “did too many people die” you are hardly going to answer “no”. He merely answered “yes” as we all would to such a loaded question.
John from accounts is probably going to lose his job as a consequence of the epic economic fallout from this hoax of a virus.
If only complex viruses and the socio-economic fall out were so simple as to be a binary question of innocuous (sic “hoax”) or fatal. Alas not…
Come off it! This whole thing has been one giant spoof as FB says.
40K dead in the UK, the vast majority of whom are old and knackered, as am I. No wonder my grandchildren call it the “Boomer Remover”. We have had our lives prolonged by many years due to medical intervention, thank you but, frankly how selfish can we be? Moderation in all things as the Ancient Hellenes advocated is the correct course of action. So no need to weep for us, we who have been so busily plundering the planet for the past seventy years and more.
What is atrocious is that the lives, hopes, and aspirations of the younger generations have been irreparably trashed by this most manic response to what, at the end of the day is only yet another whiff of Asian Flu.
What has not been addressed is how long the ‘young’ will tolerate the existence of that pestilential hell hole, otherwise known as China.
No one denies that China has been the been primary source of plague after plague since almost the beginning of time.
Are you going to do nothing and just wait for the ‘next’ one? Or take action while you still can. A Darwinian binary choice as you might say.
Consummatum est.
That’s a rather racist comment Mark. As yet we have no idea where “covid” really came from. We do know that western media seized on it and created panic around the world, causing these destructive lockdowns.
I,as you might expect completely disagree. This plague, like most in history is clearly of Chinese origin.
There is obviously something wrong with the place. In the past we could tolerate, even indulge such a diseased swamp. Now, in the new Global order this is no longer either desirable, or even possible.
However I do agree with you over the absolutely pathetic, panic ridden response of much of the West to this plague. An astonishing case of collective Lack of Moral Fibre.
No wonder the Chinese are chuckling over their Bat soup, Fried Dog with bean sprouts, washed down with Tiger testicles and Rice wine.
So when we are asked to explain the difference between the severity of Covid19 in the UK and Germany we have two possible explantions.
1) the different way that the epidemic was handled in the two countries, timing of lock-down, effectiveness of testing and tracking etc, not to mention competence of government.
2) some kind of biological difference between the German people and those of the UK in that the former possess some kind of biological “dark matter” (mysterious and unknown so far to biological science) enabling the Germans to have a resistance to Covid19 that we don’t.
As there are no significant racial differences or fundamental differences in life-style food etc between us and the Germans, I would suggest that explanation 1 is a rather better hypothesis for study
Apart from the professor’s modelling suggests 1 makes little difference. I think he’s likely to be wrong on care homes. I hope he is right otherwise, though.
I am seeing no suggestion in the piece that Friston has done anything other than simply state a proposition that some kind of biological/genetic factor can be in place to explain the quite striking difference in the rates of infectivity and death caused by Covid19. “Immunological Dark Matter” is no more than a conjuring trick with words to invent a concept. The differences noted in BAME sufferers may well be explicable as a consequence of BAME people being a the sharp end of things when it comes to likely exposure. (occupations, larger households) It should be noted also that an unchecked epidemic will not act linearly in terms of numbers but exponentially. The difference in our rates and that of the Germans is easily explained if new infections are doubling every few days.Immunological Dark Matter should probably be relegated to science fiction.
We should allow for the fact that the immune system is very complicated and even the best immunologists know only a fraction of what really happens within it. A bit like cosmologists, or whatever they’re called, and their dark matter.
Sshhh, some of the ordinary people might be reading here. Scientists know everything that matters! They aren’t called experts for nothing you know.
It would be interesting to know whether the resistance to infection is only in ethnic Germans, or whether ethnic minorities in Germany are also partly immune.
By ‘coincidence’, 80% of passengers & crew on Diamond Princess cruise ship (almost a laboratory experiment) did not catch the disease, about 50% of positive testers were asymptomatic, the very young unaffected, few serious cases and very few deaths confined to the upper age group. (Similar results from French and US Navy shops.)
Statistics closely matched by observation from experience. Perhaps if politicians had heeded empirical evidence instead of astrological forecasts based on assertion and assumptions leavened with guesswork, we would not be in this mess.
Supposedly lockdown was to slow the spread (but didn’t) to protect the NHS (not needed), what is stopping the spread (too late!) supposed to achieve?
The Covid slaughter ground is hospital wards and care homes, not the general population.
Unherd seems to have a very strange new outlook in this issue.
In this article there are quite a few prejudices e,g calling UKIP an alt right party drawn from the lowest of social classes. That does not sound ljke a party that has had many local Councillors and also MEPs.
There are educated people who many would call alt right or alt left but who are not actually extremists . Obviously the author also has a prejudice against Tommy Robinson.
No this kind of journalism is disappointing/
The author hasn’t managed to abandon her biases. The alt-left have undoubtedly absorbed the propaganda spouted by the educational establishment today.
I’ve clashed with quite a few on social media and most are to put it bluntly are bigots who are unable to construct a sensible argument that isn’t based on infantile emotional responses. Even when presented with overwhelming evidence that they can’t refute they simply double down on the insulting labels.
There are plenty of well paying jobs available for intelligent individuals but hard graft is beneath them. Ever tried to get a gas engineer for example.
Regarding regional latitude, a researcher named Hope-Simpson (yes, a Brit) spent a good part of his career studying what to him was an obvious “seasonality” and dependence upon solar radiation in the susceptibility of various different populations to influenza and other respiratory infections.
The noteable thing is that he died before cutaneous production of vit D, stimulated by UV-B radiation from the sun, was discovered or at least first experimentally reproduced and observed in the lab (rather late in the 20th century, somewhat to my surprise). Yet he published a large amount of literature based solely upon his observations, and had figured out the large correlations (both seasonal and geographic) with the position of the sun in the sky.
Contemporarily, people should not be Pollyannish about the enormous opposition to oral supplementation with vit D3 which is most certainly necessary to avoid insufficiency of hepatic stores for the vast majority of people on earth today, by commercial and similar powerful interests. These include the medical and pharmaceutical industries, governments (much of which exist to regulate medicine, pharmaceuticals, etc.), and academia. We evolved largely near the equator, with far less of our skin covered, and so forth — that is why we should orally supplement up to 30ng/mL serum 25-hydroxy vit D (the best biomarker for magnitude of hepatic stores, which is what matters) at least.
It is very easy to produce observational studies that make vit D look ineffective or trivial. These tend to be junk studies at best, and fraudulent quite often. Good studies require significant funding and a lot of high-quality work and effort. All of the funding sources for such, these days, come from opposing interests.
In fact, I have absolutely no doubt that if governments were simply to embark on a public campaign to increase vit D status, this would almost eliminate seasonal flu as well as have almost eliminated CoVID-19 before it even got started — that is, it would have been taken in stride rather than generating massive fear.
It is interesting that Germany has better vit D status than UK. I would have to assume that is due to better oral supplementation — i.e. the Germans must be better educated on this matter.
At the molecular/immunological level, it is also well known why vit D status would be so important for a virus primarily replicated in lower lung. The so-called AMPs (antimicrobial peptides) element of the innate immune response is very important in these tissues (i.e. alveolar). This is textbook material — not new, not controversial, but basic and long recognized and studied.
Vit D is a co-metabolite of the AMPs (e.g. beta defensins, cathelicidins). In the event of a viral invasion and replication in cells, this means that required supply and consumption/drawdown will rise to a proportionally (to viral load) high magnitude in response to infection. If hepatic stores are inadequate, the whole immune response will be degraded or fail.
As we age, we generate and absorb (from gut) vit D less efficiently. This is probably just one of the reasons why children’s immune response is so effective, and why there is such a remarkably strong correlation of susceptibility and age with CoVID-19.
The role of vit D has been studied now, directly or indirectly (as by Hope-Simpson), for over a century. It is not really a mystery how important it is for innate immune function. And nothing but a robust innate immune response is required to deal with SARS-CoV-2, unlike with flu. Adaptive response, medical interventions, and the like only become important if innate immune response is abnormally (relative to evolutionary context, if not to modern urban environment) or unhealthily weak.
There has already been quite a lot of observational-study literature published just on CoVID-19. I have read some of it, and some of it is pretty compelling. But I didn’t need any convincing in the first place, having studied this for years before.
The persisting amount of ignorance wrt CoVID-19 is simply stunning, given that nearly the entire world has voluntarily locked itself down with damage to lives and livelihoods that are almost incomprehensible.
All of the above, for example, is fundamentally not speculative or very hypothetical — it is pretty much longstanding knowledge. Maybe not widely spread knowledge today (partly due to its being forgotten), but not really very questionable (everything in science remains questionable in perpetuity, strictly speaking, and so I am just making a relative characterization).
Much earlier in the epidemic I sent out email advice to a long list of my friends and relatives, including a recommendation to achieve vit D sufficiency as a preventative. For those who might become significantly ill I purchased a personal supply of L-glutathione probably adequate for recovery in ten to twenty-five cases (likely adequate as a sole intervention without need for professional medical support), and also recommended that people should be aware that high-dose IV-administered ascorbate appears to be very effective as a therapeutic. The problem with the latter intervention is that it does require clinical administration. And as with vit D, the medical community is death on vit C for the most part, for much the same reason.
Fancy vaccines and pharmaceuticals may have some efficacy if and when they become available, but they are completely unnecessary for this virus. What is already available, nonprescription and dirt-cheap, is all that is needed IMO.
“It is interesting that Germany has better vit D status than UK. “
It is a well known phenomenon – Just Google: Germans Towels Beach – to see where they get their surfeit of vitamin D.
What seems to me to be a glaring omission is the failure to ask the professor one of the central questions – about the reliability of the data the government/ONS etc are giving us; which includes the reliability/trustworthiness of the testing procedures and the known distortions in the ‘covid’ attributions of cause of death.
If these factors are not included in the models how can we possibly have any trust in what the modelling says?
One thing that disappoints me about the Government’s response is that the emphasis on testing seems confined to the matter of how many tests are being conducted. There is very little being learned about what the results tell us, and how we can improve the campaign against the infection thereby. If all the tests are telling us is that x number of individuals, most of whom presented with symptoms of the infection, are infected, then we might as well not bother. My suspicion is that testing in itself is a visible case of ‘taking action’, just as initialling the chart at the bottom of the bed, or the card on the wall proving that the toilets were cleaned at 10am. I suggest that operations which are task based, rather than results based, look like little more than window dressing.
Number of tests tell us (nor the statisticians) nothing, when individuals may be tested several times during the course of an investigation, How many times were Boris, or his immediate contacts, tested?
Ferguson has a long history of seriously overstating death rates. I wonder if this is the reason why?
Whatever the effect of putative “immunological dark matter” it isn’t understood and didn’t prevent the rate of infection from threatening to overload the healthcare system – the rate of hospitalisation was bad enough at peak in the UK >2500 people per day for 10 days.
Friston discounts behavioural factors without them being properly understood while it is known reduced contact through social distancing, in particular staying at home, does indeed lower the rate of infection. There is no experimental population based evidence for any “immunological dark matter” effect YET. So in the absence of not knowing the factors that work while social distancing appears to work it is prudent to stick with what appears to work. The alternative is to expose people to infection at a population scale and see what happens – which is unethical and potentially political suicide. The hypothesis of an unknown non-susceptible subset is worth testing but won’t be able to be tested rapidly.
Again the empirical data from China on hospitalisation and death rates – which was the best available evidence at the time – was sufficient basis to be concerned that the infection left unmitigated could threaten the health the health care system as it did in Wuhan and Italy. A rebound in infection rates in Iran shows that there are susceptible people to continue growth. The most parsimonious explanation is that people’s behaviour has changed and people are infecting each other. People’s behaviour can effect the rate of spread of a virus – New Zealand appears to have eliminated the virus and Australia is getting close (despite entering flu season).
At the moment there is no scientific justification to allow infection to spread on the basis that some wall of invisible currently untestable “immunological dark matter” will prevent damage that we have seen with even small amounts of the populations around the world getting infected. I would prefer to use the observable empirical effects as a guide over an as yet untested hypothesis.
Quite.
Well, I don’t agree with the tenor of this piece. Trump quite rightly here draws other people’s attention- ie the rioters and looters – to the Bible. He is standing in front of a church, one of quite a few, that they have attacked. Quite right to remind them of the importance of the Bible and of Christianity, the religion after all on which the USA is founded.
Well said, Penelope! If rioters and looters did to Gilles’s church what they did to St. John’s Church, who would his anger be directed at, the rioters and looters, or a British pol who drew attention to it?
Sadly, many so-called priests in the Church of England are biblically illiterate. I come across them all the time in my work – it is an uphill struggle, because they never learn. Unfortunately, however, these types of arrogant cleric appeal to the media and are able to carry on with impunity, using their dog-collars as an excuse to spread hate rather than love, ignorance rather than understanding. The result? The Church is practically empty (this was already the case before Covid) and in my area only one church is left, while synagogues are thriving and growing.
https://www.christiantoday….
What needs to be reflected in any model for SARS-CoV-2 is what has been shown in the data from the peak(s) until now. That is a steady and continuous decline in infection rates which shows no sign of leveling off significantly above zero as yet.
To the degree that lockdown measures can be expected to have an effect, this would be a mere step change. That is, a rapid or instantaneous drop to a new lower level.
That is NOT what is going on. And there are no significant resurgences occurring with release of lockdowns anywhere, as far as I (and many others) can observe. Politicians are oblivious, nevertheless.
In Massachusetts in the US, where I live, our epidemic has lagged that of NY by several weeks. NY just reported its first day of zero deaths. In MA I would say that our infection rate reached ~20% of the peak a few weeks ago (mid-May, probably six weeks after our peak).
These are huge declines, and they are continuing. They have absolutely nothing to do with lockdowns. They are occurring everywhere in the world except in regions that have not yet had significant infection/exposure. In a few regions this inadequate exposure is due to successful early containment measures, and in others it is simply due to lower population densities and travel and such.
Unsurprisingly, in those regions with successful early containment, outbreaks have been persistent. South Korea is an example. In China it is a mixed bag. They peaked before lockdown in Wuhan, and so reached a better level of exposure and are doing OK there it appears. Since their data are fabricated and fraudulent it must be ignored, and crude observational inferences are all that can be gleaned. In Guangdong and other regions of China epidemics appear to be persisting at higher levels than in Hubei. Even in Wuhan the Chicom’s are attempting to antigen-test every single resident — why?
Monitoring Italy may be most useful at this time, and its epidemic peaked earlier than others in Europe and in US, so at least in Lombardy it is ahead of most in its population response. I find the comment by the clinician from Milan, that the typical viral load there is now “infinitesimal” in comparison to that just a month or two ago, to be seminal. This will happen in London and NY and Stockholm soon enough too.
Once more about this virus is correctly gleaned or learned through difficult and painstaking and persistent study and experiment (with the biology and not just computer programs), the underpinning of this observation will be elucidated. What is clear to me is that this effect is due to the human immunology that is built into our common genome, and its method of response to this unique virus, which is very different from flu. There is a different balance of roles of humoral and cell-mediated and innate immune responses, and there is a difference in sensitivty and selectivity of tissues viable for intracellular replication, and hence in transmissibility properties.
David Heymann made a cryptic remark to this effect in a discussion with Johan Giesecke, noting that the transmission of this virus is different than that of flu. I think this is right on the money. PIty that he did not elaborate just a bit more upon his thinking, but I suspect it is the same as my own based upon the same limited observations.
With respect to Friston, he misses the important thing in the data which is the intrinsic natural survival feedback in our species (and almost all others extant) that makes it robust/stable rather than fragile/unstable. That is why the decline of the contagion is inexorable. All stable and robust physical systems have this property — both biological (e.g. animal species) and inert (e.g. earth, which is our vital environment). In vertebrates the negative feedbacks are comprised of the adaptive immune system, which include capacity to recognize and memorize viruses with high specificity/selectivty. In invertebrates it is a different system, and lectins substitute for lymphocytes for example. All organisms must survive and tolerate infection by viruses, however, and do so. Host bats do not need even need to eliminate coronaviruses, and tolerate them as permanent residents.
A final point that I think most, including researchers, fail to understand is that elements of the human immune systems (e.g. lymphocytes) do not work independently. There is a highly complex system of signaling between and amongst them.
The humoral response (I.e. B cells and antibodies) not only coats and disables, but also labels antigens (i.e. virus) for destruction by killer T cells and neutrophils and NK cells and macrophages and so forth. The cell-mediated response, via regulatory T cells, plays a powerful role in coordinating (i.e. regulating) the response of innate-immune lymphocytes. This is partly why we see “cytokine storm” (cytokines are a key basic system-wide signaling molecule of the innate-immune system, calling for resources from liver and other key organs and attracting these to sites of infection) in the weakest and most susceptible with advanced complications, and no such thing in the strong who recover readily with or without any medical intervention.
IMO phenomena like cytokine storm are simply a symptom of an immune system which has fallen behind in the race between virus (and its replication in cells, which destroys their function and viability) and immune response. Attempts to suppress or “modulate” it using drugs are naive and generally ineffective.
What needs to be avoided in those not already near end of life is damage to their immunological competence and cellular health that are our birthright, and which almost all children start with. Vit D adequacy would be a tremendous and simple first step. Better emulation of human-evolutionarily appropriate diet would be a more difficult one at societal level, but not as difficult for a free individual person with sufficent wherewithal.
For near end-of-life, adequate isolation is the best option. We all die eventually because our cells lose viability — we lose sufficient cellular health to remain alive. Preventing infection by CoVID-19 might prolong life a bit. The elderly very often die of pneumonia, and almost any common infection can and does cause this. So isolating the elderly is easier said than done, and CoVID-19 will be only the newst of all sorts of common infections that may cause death. CoVID-19 does not change the overall picture much.
If the majority of the population gets healthier this may have more protective impact wrt to the elderly than any isolation measures. It will reduce death from flu and other respiratory infections too — not just SARS-CoV-2.
A successful virus-specific vaccine may or may not be produced. There is a good chance it will, only because of the tremendous amount of resources being thrown in. But vaccines are quite likely not to make much difference because the pandemic will already be mostly eliminated, at least in many more populous areas. An impact in the less populous and poorer lagging (in exposure) areas is likely to be bigger.
Meanwhile, societies will likely continue to degrade in typical health and immune competence.
Your argument that human population is a strong system with innate self-stabilization qualities would seem to be refuted by the mass deaths due to pandemic found throughout history, as well as other mass death death episodes. Unless you are referring to the concept that people were describing Covid as an existential threat to the human race, and I don’t recall anyone seriously arguing that.
The fear was that this would result in mass casualties of the type common to human societies in even the recent past, but which have come to be considered as something to be avoided if possible.
So far, the evidence seems to me to be that this is a very bad disease, at least an order of magnitude worse than flu in terms of IFR.
What is unknown is the explanation for the dramatic differences in outcomes in superficially similar populations. The above interview amounts to this simple observation.
Since even after 5 months of intense study this is poorly understood, I don’t see how anyone could have possibly predicted this.
A well-presented, coherent argument – from statistics. But how can this influence my personal decisions and actions? I’m not a statistic: I have 100% of one life. Do I have this ‘dark matter’ or not? What test will accurately inform me?
And somehow the Danes, Norwegians and Finns possess this ‘immunological dark matter’ but not the Swedes?
The Danes and Norwegians are different Scandinavian nationalities from the Swedes. The Finns aren’t even Scandinavian in the majority (although a minority actually are ethnic Swedes). All of the countries have immigrant groups that are neither Scandinavian nor Nordic, and in Sweden, Somali immigrants have become a particular topic of contention since their infection and death rates are much higher than the Swedish population in general. Sweden has a more important Somali share of its population than Denmark or Finland (although somewhat smaller than Norway’s) and arguably the most poorly assimilated Somali immigrant population of any of the four countries. So what would seem to be your assumption, that these four countries are identical in race and social behaviour, is badly flawed, even if Friston had said that these were the only attributes defining “immunological dark matter”, which he does not.
Norway and Finland have almost certainly suppressed their infection rates with early lockdown intervention. And a base level of relatively low cases.
If the darkmatter theory is correct, these two countries will see more flare-ups when the borders with Sweden are opened.
If a vaccine is a available late 2020 or early 2021 then their public health choices will compare favourably to Sweden’s.
It may well be lots of different sorts of “dark matter”, rather than a specific genetic item identifiable by a simple test. But in any case, if Friston is right in discerning the influence of these stable unidentified defences, it follows fairly immediately that you will benefit from the threshold for conventional herd immunity being 60 per cent of 20 per cent (or whatever, depending on the actual value of R0) rather than 60 per cent of 100 per cent. And it is plausible that this lower number, call it 12 per cent, is what is being attained globally. So you would’t need to wait for a “Friston Test” before going down the local for a pint, if the local were open.
That’s requires risk management. You could stay in the house all the time and get electrocuted by your kettle developing a fault or fall down the stairs and break your neck or that pain in your left arm, is it a heart attack or the result of an itch, and on and on it goes. Life is full of risk, being afraid of them doesn’t change those risk, staying at home in lockdown creates other risk that are equally as dangerous – mental health, lack of exercise, not going to the doctor for other serious conditions, etc
I suggest that Boris calls this chap as a defence witness at the forthcoming public enquiry.
How very mainstream, echoed from other media-spheres. A white-noise of outrage to drown out any countervailing argument. How easy it is to concentrate all the woes of America into a single individual. What I am not seeing in the article is any liberal self reflection in their part in ensuring the racial fault lines are perpetuated for political gain. The article is loaded with cyclopean vision and straight out of the Al Sharpton victimhood manual.
I find the dems are destroying democracy at a MUCH faster rate.
Prof. Friston is probably on the right track, but I hardly think that one should need to use terms such as “dark matter”. The idea that there is already a lot of adaptive (cell-mediated, via T lymphocytes) immunity as well as innate immunity in populations is almost certainly correct, as I have suggested many times already in comments. This is all VERY basic immunology.
I am not at all sympathetic to the idea that Levitt’s notions are creditworthy, on the other hand. Indeed, they represent the fundamental problem of misunderstanding on the part of so many, amongst them people calling themselves epidemiologists. The idea that any epidemic response could remain significantly “exponential” (or geometrically progressive, to be more mathematically general and accurate — Ro is not necessarily 2.71828…) once spread becomes large enough to be detected (and hence, stat’s recorded) is absolutely absurd, and hence should not be at all surprising or noteworthy. Our species would have long ago become extinct if this were possible. It is not, as I have explained in earlier comments.
Levitt also seems not to have recognized that the CCP stat’s he followed are pure propaganda, likely generated by a spreadsheet. But in any case, implausibly small in a city from which an exodus of half of the population had already occurred before the authorities had even attempted to intervene, much less implement lockdown. How many deaths in the streets would have been necessary to induce 5 million residents to flee in fear, completely of their own volition? Why is it that academics (those whose finished product are ideas, almost always untested and usually untestable), as opposed to intellectuals (those who actually think, and do not earn their living by selling ideas), seem to be so lacking in basic common sense?
One of the clear problems for many seems to be assumptions of similar or equivalent epidemiological characteristics to those of flu. I don’t think there is any other respiratory virus for which there has been enough study for much understanding, other than flu. And I doubt that ANY other virus is very similar, in fact.
A case in point is the common presumption that 50% to 80% of the population must be exposed before significant herd immunity is developed. This is, I think, based upon flu and only flu. And I think it is probably wrong for SARS-CoV-2.
” ‘In reality, the virus clinically no longer exists in Italy,’ said Alberto Zangrillo, head of the San Raffaele Hospital in Milan.” Zangrillo was referring to viral loads in recently tested CoVID-19 patients as being “infinitesimal in quantitative terms compared to those carried out a month or two months ago”.
Quantitive (as opposed to qualitative or yes-no) observations such as Zangrillo’s are exactly what is so often missing amongst medical pro’s today. And clearly there is an immunological response at population level that is responsible for the time profile of typical viral load observed in CoVID-19 patients, especially since it shows such a huge dropoff. Viral load will translate to both rate and magnitude of transmission.
With both SARS-classic and SARS-CoV-2 there were a lot of medical pro’s, many of them quite young, who died themselves after being exposed to some of the earliest cases in the cities of origin of the epidemics (in mainland China, in both epidemics). It is true that some of these medical people might have lacked proper PPE, but I wonder whether that is enough of an explanation for the phenomenon. And many of them knew exactly what they were doing — i.e. they knew they were investigating a novel virus from the beginning.
SARS-CoV-2 is not flu — not by a long shot. The detailed immunological and molecular mechanisms will probably be worked out over the next few years, but whatever increases in immune resistance have already been achieved in all of the countries and regions that have had relatively unsuppressed contagion have clearly developed a powerful level of herd immunity. There is no other explanation for the uniform shapes of the curves everywhere.
In Massachusetts, where I live, the inexorable decline in apparent infection rate and in deaths continues apace (no more than 20%, but probably less, relative to peak). I am beginning to think there may not even be anything but a trivial 2nd season (in the coming late fall and winter). But this seems the same everywhere, except for the few countries who were successful in early containment.
Of course, as should have been expected, many of those countries are having outbreaks. South Korea is the poster child, I guess. Other than to have bought time, I think the idea that countries will be able to lock out the virus indefinitely is completely absurd. And really, most healthy people should have absolutely no fear of infection — they should welcome it. This is the best thing in the interests of their societies at large.
A valid epidemiological model should explain Zangrillo’s observation, I suspect. I tend to think that the Oxford Univ. model is not quite right — i.e. I suspect that most of most populations have not yet been infected/exposed. But Prof. Gupta is on the right track, and trying to come up with a model that explains the most basic observations. I do think that a significantly larger percentage has already been infected than can be demo’d by serum antibodies testing, but maybe not more than 50%. Many of these people were probably asymptomatic or had mild symptoms, and the spike glycoproteins are well known as weak humoral antigens. But some cell-mediated immunity would have developed if any cells replicated virus. This is what Friston is suggesting, and there is no question this is correct — the only question concerns the quantities, and nobody yet knows these, and they will be very challenging to measure because there are no known methods yet in existence. Friston’s notion is very similar to Gupta’s, if not identical. I think it is close, but not quite right.
My idea is that one of the negative feedbacks of the population-level immune response is indirectly to transmission/transmissibility — as the population develops some immune resistance to the virus, this attenuates the amount of virus replicated in respiratory tissues, and this in turn means that fewer successful transmissions will occur and those that do will result in lesser symptoms and quicker recovery by those infected. I do not think that this effect is likely built into any epidemiological models for flu (and that might be appropriate), and hence any for SARS-CoV-2 (which may be a big flaw for this particular virus and its multiple differently-susceptible/potent tissues of replication and hence multiple modes of transmission from upper, upper-lower and lower-lower respiratory tract). And if one thinks about the implications for a chain of many individuals, this would be a powerful and geometric effect — sort of like daily interest-rate compounding year after year. Heightened immune response in only 20% of individuals in a long chain could have a huge effect for those far down the chain.
As I have thought from earliest on, SARS-CoV-2 is a fundamentally weak pathogen. Not even remotely comparable to flu (for which the 1918 pandemic is the appropriate measure of comparison, when flu was still novel). Its epidemic consequences are likely to largely die out before any vaccines or therapeutic interventions have any chance to play much of a role.
“there is no question this is correct” then and “nobody yet knows these, and they will be very challenging to measure because there are no known methods yet in existence.” that’s called faith, not science.
I got a far better idea about Professor Friston’s model reading this short paper
https://theconversation.com…
than in watching this entire interview.
I understand there a lot of people with vested interests who would like what he says about limited susceptibility to be correct – indeed so would I – wouldn’t it be great? However his models are no less flawed than anyone else’s and there is no clinical evidence to support his theory. This site appears to have a particular agenda and a readership to whom it appeals, but let’s not kid ourselves that there is some clever science validating our particular beliefs which must be correct whilst all the other scientists must have got it wrong.
Indeed, if Professor Friston were really convinced himself, wouldn’t he be making a bit more noise about his discovery? Along with many others who’ve read his paper? Wouldn’t the Independent Sage group be making a lot of noise about it too, rather than advocating a delay to school openings?
Interesting points.
About a month ago Dr. Muge Cevik of the University of St. Andrews tweeted information from various studies following up on close contacts of COVID 19 cases.
One striking thing about them to me is the relatively low rate of infection among members of the same household. All studies found infection rates below 20%, and some were in the single-digits.
(Granted, the linked studies also included a couple examples where the rate was well over 20%. Individuals at a large homeless shelter (about 400) were tested over a couple days, and 38% were positive. All residents of a nursing home were tested a few weeks after the first known case there, and 64% were positive. I suppose, however, a hypothesis is that both groups might be relatively susceptible to infection due to factors such as ill health or poor nutrition.)
The household findings don’t make a lot of sense to me. This is a virus where we also have reports such as several people one table over from an infected diner becoming infected due to the flow of air conditioning, but the vast majority of people living in the same household don’t become infected? That combination doesn’t make much intuitive sense to me if the entire population is generally susceptible to COVID-19. It makes a lot more sense if we consider the possibility that some significant number of people aren’t susceptible to infection (or, at least, require extremely high viral loads to develop an infection.)
Edited addition: link to Dr. Cevik’s tweets – https://twitter.com/mugecev…
Not the winter immediately past but the one before there was a ‘cold’ going around that had symptoms rather like a minor attack of covid 19. In particular it produced a very persistent dry cough. Not a scientific fact, I know, but what Prof. Friston says doesn’t surprise me. The fact that little children continually pick up so many minor respiratory ailments might be the reason that they too seem to be almost immune to covid 19. If there is ever a proper inquest into the handling of covid 19 it might conclude that shutting schools had far more downsides than benefits. I know that a biochemist of my acquaintance with three little children was utterly exasperated that schools were closed and considers the ‘social distancing’ measures now in place when schools reopen is bordering on insanity.
A great interview which just shows how this is evolving and how much is influenced by emotion rather than reason
Off the top of my head I’d say that you can convince about 5% of the population through reasoned discourse alone.
I am very surprised at reading this article in Unherd , such indictment not only of Trump but of the Republican Party /I think there should be one indicting the Democrats , who seem to have been taken over by the so called progressive (i.e regressive) left and Islamist, like the woman Omar . The Democrats currently supporting rioting and looting in the USA and supporting the Antifa who are involved in this.
Surely all science is faulty to some degree when looked at with hindsight. Governments had to act on the science that was available at the time, and that had the broadest support amongst the scientific community. What we are going through is a learning curve that will hopefully benefit humanity in the future.
The implications for what happens next if the “dark matter” / non susceptibility theory were proved are profound. If there is a will to look, I am sure the “dark matter” can be found, unlike real dark matter – maybe in people who have tested positive, but been asymptomatic? I have been convinced for a while there is more at play than antibodies. Stockholm’s surprisingly low antibody rate, when compared to London and New York must have some sort of population differential explanation and even the London and New York figures are lower than reality due to false negatives (the inevitable implication of eliminating the possibility of false positives).
The key question is, will the real SAGE be prepared to actively look for the explanations. It should have nothing to do with a pointless arguments about whether what has been done was right or wrong (we can change what has been done and nobody could have been expected to know something which even now is only a theory built on having enough data following peaks) but all be about getting us out of lockdown and rebuilding our economy. If the price of that is that the vulnerable and susceptible have to stay in their arks, then so be it.
I assume you mean we can’t change what has been done.
Ian, you lost me at “curse of racism”. I understand it feels this way. I understand that an image of a white cop with his knee on the neck of black man invokes an emotionally-charged visceral reaction, which compels folks to say such things as “this is America”. Is it?
By all available metrics and data, no, that isn’t America. Not even close. And using an outlier event to make sweeping statements like America is “cursed with racism” is fallacious, and takes for granted the unfathomable improvements this country has made in race relations. These kinds of events are the exception, not the rule. Show me any data that proves otherwise.
If America is “cursed with racism”, then by that logic, virtually every other country in the world is damned with it.
I don’t like the characterization of a purported 80% (regardless of the exact figure) as being “not susceptible”. This would imply, for one thing, that the adaptive immune system (including humoral and cell-mediated responses — i.e. both B and T lymphocytes) plays NO role. If this were true then there would be no contribution to any increase in herd resistance by the same 80% of the population.
This is certainly wrong. What Friston possibly means is that the 80% will have little or no symptoms, but that is quite a different matter. If they replicate virus within cells they will develop new adaptive immunity to the virus. Most viral infections will result in no detectable symptoms whatsoever. The symptoms come from the inflammatory response (which is a normal and good thing), and this is in proportion to the viral load (i.e. amount of replication of virus). A small viral load will not be detectable, and most are in this category for flu and cold viruses (including coronaviruses) and such.
Even young children do become infected, commonly enough, with SARS-CoV-2. But remarkably it appears that they are incapable of transmission, and this is a function of viral load. Their immune and cellular functions are still pristine, and they readily eliminate the virus. And very young (i.e. less than 3 years of age) children have immature (i.e. not yet fully developed) adaptive immune (aka autoimmune) systems. And those short of adulthood tend to have less adaptive immune response because they simply have not yet “seen” as many pathogens as adults.
What this means is that the children, who so readily eliminate SARS-CoV-2, do it predominantly with innate immune response. This is very much in contrast to flu, for which children are at much higher risk, and at higher risk than non-elderly adults. This tells us a lot about the nature of the novel virus from an immunological point of view. It also shows how very different in molecular nature SARS-CoV-2 is in comparison to any influenza virus. Why should we expect it to behave like flu epidemiologically? We should not.
To give Friston the maximum benefit of doubt, he seems to define “not susceptible” as a subset of population that never replicate any virus, even if exposed.
For those who only replicate a small amount of virus (i.e. total integrated viral load) who might be completely asymptomatic (and this is very common, we know — about half of overall populations I think, but very much age-stratified), how likely would it be that they would have tested positive for RNA with PCR? Probability would be roughly zero. So I am baffled to figure what observations he would base his notion of nonsusceptibiltiy upon.
It is theoretically possible, with a tiny infectious transmission especially, for the humoral immune response to eliminate 100% of virus before any penetrates cells. This would nevertheless be highly unlikely for flu or rhinovirus or cold-type CoVs, to which there has been more than a century of continuous exposure. But for a novel virus it is actually impossible — it would require serum antibodies, and these are not yet generated for a novel virus (by definition).
For the innate immune response to eliminate 100% of virus before any cellular penetration — that is, while 100% of virus is only present in blood or lymph — is inconceivable to me, based upon human immunology. Human LDL is indeed antibody-like, but without any “learned” selectivity. It is very effective in coating bacteria in lymph, and has a number of known mechanisms of action. Some efficacy against a few viruses has been observed, but this is not comparable to that against bacteria. Bacteria are ancient and primitive organisms that all share certain properties, and this is what allows an innate-immune mechanism (such as LDL) to have evolved over hundreds of millions of years, and to work. That is not true for viruses in general — they are the opposite of ancient or primitive, and adaptive response is really required for recognition. Viruses are not living organisms — they are just little scraps of biochemical/genetic material that originated at one time from a living organism, and have been “adopted” in other “host” organisms because they “look and function” like normal cellular/cytoplasmic molecules containing genetic (i.e. nucleic acid) strands. One virus cannot be expected to have much of anything in common with another, and they all look “normal” while still merely extracellular, unless virus-specific antibodies are present.
But once inside cells, where they are replicated, then they will be detected by T lymphocytes because of cognate-antigen presentation on cell surfaces that reflects the abnormal or foreign nature of the cell’s replication of the virus in large quantities, and with a signature not normally “seen”, unlike the constant signatures of normal cellular metabolism. And innate-immune lymphocytes (e.g. NK cells) will be signaled or recruited as well.
I would have to opine that Friston’s notion on nonsusceptibility, meaning (I think) a large proportion of population that cannot replicate virus in tissues at all, cannot be correct. It is not possible based upon what is known of viruses and human immunology IMO.
But also, I do not think that this notion is at all necessary to explain his observations, such as the difference in susceptibility between Germany and UK, or amongst different societies in general.
All that is necessary is a difference in metabolic health, or competence of INNATE immune response, which are related. These are DEFINITELY different amongst societies, and amongst individuals within a society. Age, just for one example. Latitude for another. Comorbidities (CVD, T2DM, metabolic syndrome, obesity and hypertension) too.
Vit D might be either a predominant reason between Germany and UK, or only part of the reason. If the German diet is significantly healthier on average (i.e. more similar to that we evolved with), for example, that might be another factor. The predominant reason for poor metabolic/cellular health and function today is modern urban/industrialized diet.
Friston seems relatively more interested in what I would term the “static” differences, and not very much interested in the “dynamic” differences.
The static differences would relate to innate immunity and to magnitude at epidemic peaks, or area under the curve.
The dynamic differences would relate to adaptive immunity (i.e. B and T lymphocytes) and to the shape and duration or time profile of the curves, independent of magnitudes.
Any TRUE epidemiologist understands these basic principles of immunology, I think. Certainly Gupta and Geisecke do, based just upon their interviews. It is not clear that Ferguson does based upon his interview or his modeling, but if he does not I would not consider him an epidemiologist as opposed to someone simply playing with computer programs without any understanding of the relevant biology.
What governments and various so-called “experts” (whom I refer to as key opinion makers — i.e. hired propagandists, really) have gotten so thoroughly and catastrophically wrong is the DYNAMIC aspect of the modeling. I don’t find the static aspect very interesting or noteworthy. The relatively trivial susceptibility to flu and other respiratory viruses in India has been noted for decades (maybe even centuries I suspect) — this is not new with SARS-CoV-2! I would be very surprised if flu susceptibility in Germany is not similarly lower than in UK as for SARS-2.
The negative feedbacks determine the shape of the curves, and come strictly from the adaptive immune response of the broad population — not from the innate immune response, which is sort of the baseline but not a dynamic (i.e. time-variant) epidemiological factor. And not from the lockdowns either, to be sure.
If Friston or Gupta prove to have been wrong we’ll all be glad that they weren’t the scientists the UK Government chose to listen to. I wonder though whether they’ll be as willing to come forward and give interviews admitting they were wrong or will they just quietly slope off and hope that people don’t remember what they would have had the Government do. It’s too early to know who’s right, Gupta, Friston, or Ferguson. However, you can see why if it’s your job to advise the Government on what action to take, you’re more likely to to go with the worst case scenario than the more optimistic ones. Gupta and Friston have the benefit of knowing that they won’t be held accountable for hundreds of thousands of deaths if they are wrong.
I did entertain such idea from the start, and find it very credible. As a data scientist I was rather sceptical of the models concocted by virologist and medical experts, I felt that data scientists had much to contribute but had been overlooked (I guess because few have the prefix Sir or prof before their name and teach at Oxbridge or Imperial College).
That is why after few weeks of the lockdown (I was waiting for enough data to be available) I started looking for data to build an alternative (data based) model using actual data of how the virus was affecting the population in all its aspects: age, gender, location, hospital
trust, care home, etc. None was available from the NHS or Public Health England, and when I asked the ONS, there was a ‘ we will respond in five days’ response – they never did.
This seems feasible to me. We won’t know – in any real scientific sense – for at least months yet. That is the problem with using scientific method, you cannot progress more quickly than the latest proven technology will allow. It’s still better than any other method though.
The comment about viral overload for doctors etc. struck a chord with me; it seemed the only explanation I could think of why so many of them got infected, & subsequently died,when the pandemic struck.
Is this why that disastrous “Spanish Flu” had a second wave? That, as now (perhaps), there was an immune majority to the first wave but that the virus mutated slightly to bypass the immunity, causing a massive loss of life.
It seems that without a complete understanding of the viral mechanism to explain it all, which we don’t have, brilliant statistical explanations are always possible.
My impression is that the Spanish ‘flu of 1918 was a quite different infection; it affected the young and strong, while Covid-19 mostly affects the old and unhealthy. Which suggests that the mechanisms of infection and resistance are quite different.
Of course, we can’t say for certain, which is why the ‘second wave’ idea cannot be completely dismissed. But, from what I’ve read, there seems to be more serious opinion against a second wave than for one.
etiology of the infection has NOTHING to do with the mechanism and severity of the disease.
Some questions which should have been asked/properly answered:
1. Is it legitimate to use testing data across countries, given the vast variations in this, and that most places (perhaps not Germany) “give up” on testing when their epidemics take hold and its just not feasible anymore? Or is the reference to the limited and highly unreliable (according, say to Gupta) antibody testing which has occurred?
2. Similarly, the answer to the question on which countries were used was elided. In countries such as India or those in Africa, even death data (of any death) is not reliable. Surely cross-country comparison suffer from the problem of far too many differences in nature of the data?
As I posted in response to your article on professor Gupta’s views (though you deleted it as spam, to which it bore no resemblance), it appears that a test to ascertain whether a person’s immune system will be able to cope with the virus regardless of whether he has previously been infected with it would be most useful. Only the rest would need to be locked down while herd immunity built in those able to cope with the virus.
I’m amazed that the author did not mention that Trump keeps his mothers bible – in fact he had it placed on top of the US Inauguration Bible at his inauguration. The bible in the photo looks old & may possibly be his mother’s.
While I found this interview really interesting and very thought provoking, we are still talking about theories here, and nothing factual. At this point, we don’t even know whether people who have had COVID19 acquire immunity, or if so, for how long. In the case of American meat packing facilities, a majority of people working in close quarters have become infected with COVID19, so how does that fit into the 20% susceptible theory?. And during the interview there was no definition given of susceptible vs non susceptible people. What is non susceptible? Carriers who don’t get sick? People who are exposed and don’t become carriers? I think ultimately the devil is in the details, and only time will answer all these questions and give us the full picture of whether government has over-reacted or not. It is really puzzling that in some places, such as New York City, the health system was overwhelmed by the rapidly increasing number of cases, lots of finger pointing going on while large numbers of dead being kept in refrigerated trailers and then on to the mass burials. I think a lock down was critical to reducing stress on overwhelmed medical facilities. Mathematical models without scientific facts can be and have led to seriously erroneous conclusions. Modelers all know that when you put garbage into your model, you get garbage out. Time will tell if Prof Friston is the right track. Thank you for that very stimulating and intelligent interview.
Impressive, as always.
I have often felt the difference between far right and far left is the same as the difference between far East and far West ie a narrow strip of water called the Bearing Straits
With the dark matter theory, how do you explain that 60% got infected on that ship to Antarctica that ended up in Uruguay and only just less than 20% got infected in Diamond Princess. How do you explain that the “star of Europe”,Germany has 25 times(!) more deaths per Capita than the oldest population, no lockdown country Japan? There must be dark, darker and darkest matters……not black and white.
Ships are different; maybe the Diamond Princess has more sophisticated filtration in its air conditioning system. Which follows on to Japan, where maybe, in common with other Eastern countries, the wearing of face coverings was more widespread, even before Covid-19, as a method of protection against infections and also pollution. If there is a correlation between the amount of the virus ingested and the seriousness of the infection and inflammatory response, which common sense would predict, this could explain at least some of the difference in the death rate.
Not a good article, very poor use of the english language, if you have something to say or ask use plain english. You are probably suffering from a poor degree choice from an inadequate institution. Alt right or left is really an irrelevant social construct by moronic journalists.
I’m not sure how widespread this is and sorry if it’s a bit off topic but here in Philippines private hospitals are being funded directly from Manila government for Covid 19 related cases. I know of one such case, untested but 99% not Covid where the cost was first massively inflated and then passed to government for payment. That would be a corruption funded statistic.
I wonder if our modeler friends remembered to factor that one into the equation?
My understanding is that in the US many deaths are put down as Covid because the hospitals get more money that way. The other reason, of course, is to justify the lockdowns. Two medics who made these claims were removed from YouTube.
The excess mortality figures suggest that covid deaths are undercounted rather than overcounted in almost every country.
Yesterday I posted 2 comments which disputed the suggestion that only 20% of the population was susceptible to the virus, both referring to supporting evidence. Neither comment has made it through Unherd’s moderation system. Both comments were completely consistent with Unherd’s comment policy. I draw my own conclusions.
I’m surprised to hear that UnHerd has blocked your comments, if that is indeed the case. I have said some quite controversial things here that would never be allowed in The Guardian and perhaps even the DT. I am happy to say that my comments tend to get a lot of upticks.
Please always remember that this discussion must be lead by the two D s . Denominators and Demographics. All of infections and deaths must be the denominator and the relavant population considered should be the denominator. So if you have 40,000 deaths (denominator) that should be compared to total population (66 million) you get the most important product , which is your chance of dying.
Secondly, look at the various demographics of those that are dying ( getting the virus is bad but not enough to cause lockdowns). A quick peek will show all that if you are under 59 you have virtually no chance of dying and ditto for healthy people.
OK so we now have the :
“Karl Friston’s theory…”- what would be useful is someone who is both a good statistician as well as a good experienced epidemiologist, otherwise we might just have lies damn lies and statistics..
I still fail to see that either Prof Friston or Prof Gupta can account for the figures from New York City, where the death rate is currently about 0.2% of the entire population, and up to 0.6% of population in some Zip codes such as 11239. This data does distinguish between the Friston and Gupta models. The IFR on the Gupta model cannot be as low as the range of 0.1% down to 0.01% she postulates, and indeed she is forced to introduce some other, unexplained, mechanism to account for deaths in areas of high population density. The Friston model of 1% IFR can be salvaged on the assumption that for some reason the pre-existing immunity in New York City was not 80% but for some reason much lower, at most half that. In either case, one would expect to hear something about that. It’s clear that there’s some difference between New York and London, too.
80.8% of the sailors on the USS Theodore Roosevelt that neglected to wear masks caught the virus.
https://www.workboat.com/ne…
errrrr…
1/ these sailors were in CLOSE QUARTERS and
2/ Other notable findings include:
Nearly two thirds of service members in this sample had reactive antibodies.
44 (18.5%) of service members who were identified as having a current or previous SARS-CoV-2 infection did not report any symptoms.
Among those who provided nasal swabs, just over one third tested positive for current infection.
Loss of taste or smell was the symptom most associated with current or previous infection; participants reporting these symptoms were 10 times more likely to have infection than were those who did not.
Among 12 participants with antibodies that were detected longer than 40 days after symptom onset, eight remained neutralization positive including two participants who were tested 3 months after symptom onset.
Among all participants, current or previous infection was more common among males than females, but did not differ significantly by age, race, ethnicity, or history of a preexisting medical condition.
Current or previous infection was higher among participants who reported contact with someone known to have Covid-19 (64.2%) compared with those who did not (41.7%) and higher among service members who reported sharing a room with another service member that tested positive (65.6%) compared with those who did not.
Service members who reported taking preventive measures compared to those who did not had a lower infection rate (wearing a face covering (55.8% versus 80.8%), avoiding common areas (53.8% versus 67.5%), and observing social distancing (54.7% versus 70
Brilliant. Not going to write anything here. Far better to suggest that anyone looking for wisdom in the comments here goes, instead, back up to read the article (again).
Presumably, a proportion of the 1.5m ‘shielded’ population might also be ‘not susceptible’ to the virus?
But as infection would likely be fatal, it’s not worth taking the risk at present, is it?
That’s probably their choice, if they have a year of life expectancy left do they want to endure it shielding ?
(Ferguson) ‘was right that around 80% of susceptible people would rapidly become infected, and was right that of those between 0.5% and 1% would die ” he just missed the fact that the relevant “susceptible population” was only ever a small portion of people in the UK’.
A polite way of suggesting that the “science”, upon which our recent restrictions have been predicated, was out by an order of magnitude.
Good article, the evidence seems increasingly to point in this direction.
Is it possible, contrary to the popular narrative, that international travel and globalisation has made the world less susceptible to a global pandemic? – ie by creating a lot of global herd immunity to infections compared with the past? – could the low death rates in Asia from this virus be explained by the fact they are nearer to the origin of many of these viruses and therefore have more natural immunity to them? In the UK, like most of the rest of the world, we have a policy designed for the few, not the many, to misquote Mr Corbyn. The world was primed to react based on SARS, MERS and films (eg Contagion) and documentaries and reacted accordingly like a set of dominoes…
Comments appear to be disappearing from this site!
Frum is a Conservative turncoat as well as a Republican turncoat. His far more sympathetic sister, Linda Frum, is a Conservative Senator in the Canadian Senate, appointed by Prime Minister Harper in 2009. While it would tempting to attribute his drift to the left to Trump Derangement Syndrome, in fact he had been heading in that direction for some time. In the 2012 presidential election he said he would vote for Obama unless Romney or some other person whose name I forget were the Republican candidate. Some Republican! I don’t know about US media but Canadian mainstream media can’t get enough of turncoats from the right like Frum, giving them endless coverage under the pretense that they are giving a platform to voices from the right. Frum, while vile, is not stupid. He hasn’t torn up his Republican membership card, as he certainly should have done, because it is his meal ticket. The Frum quote BIrrell uses is hypocritical. Frum is a negative, nasty journo. These days, he never appeals to “the better angels of our natures”, or not so you would notice.
“INNATE IMMUNITY” is the first stage defence, long before any adaptive immunity arises. Perhaps we’re seeing a difference in innate immunity across the population, with a large proportion capable of kicking coronavirus into touch. Maybe this response could be measured & quantified using a dose of something less aggressive, like a common cold ?
Or it may be that any such immunity is more specific to particular diseases. But a reliable test to show a persons capacity to resist or recover from the virus would be hugely useful. I wonder whether the search to find a vaccine might be structured so as to watch for any indication that such a test could be found or developed.
Yes, anecdotally I’m sure we all know people who are rarely ill, and others who are constantly suffering with some infection or other, often for longer periods than is normal. For all sorts of reasons, the resilience of our body systems seems to be very variable.
The higher death rate in care homes may partly explicable by the lack of prior immunity in communities which, by their very nature, are not as exposed to the other coronaviruses circulating in the general population.
Is the immunological dark matter merely a telltale that covid19 has already been round the globe a couple of times in a earlier form. But on this time around some one decided to tinker with it.
P.S. A very nice explanation of “negative feedback(s)” was mentioned by Prof. Gupta in her interview. She noted that “Ro” is the intrinsic or maximum reproduction number, only achieved at the very earliest stage of an epidemic for a novel virus, while “R” is a time-variant and ever-decreasing reproduction number that is “primarily a function of the buildup of immunity in the population” (I paraphrase her, but she made a big point of this) as it is increasingly exposed/infected over time.
Put another way, Ro is a function of the intrinsic properties of the viral particle/molecule as conventionally understood, but also of the innate-immune competence of a population as well — this is not so much noted but is equally true. Ro itself is not a function of negative feedbacks.
R(t), or R/Ro, is a function of the adaptive-immune response of the population with time — that is, “R” is a function of negative feedbacks via autoimmunity that increases with exposure to virus.
That is how I might attempt to teach epidemiology 101 using the terms of the discipline. Maybe I should become a prof 🙂
Last Fall, I attended a lecture by a former FBI agent, who warned the audience to ‘buckle your seatbelts’ during the 6 months prior to the November election, because the Democrats & Left will do everything they can in their surge for power. He was right. It’s 1968 all over again. The Democrats are beyond reason.
Very interesting. However, needs to be proved before some politicians, who did not perform well during the crisis, start using the argument that “it doesn’t matter whatever any government did or didn’t do… at the end of the day with or without measures in place the results were inevitable”.
How utterly pathetic is Unherd? You block or delete comments which upset your Guardianista-bubble, soy-latte opinions. Your articles are usually abysmal – invariably so, if written by Tom Chivers. You really should be prepared for a degree of criticism, considering how feeble your writing is, but, no, reasoned criticism is met with Stalinist censorship.
That’s how pathetic Unherd is. If this comment is allowed to appear at all, I expect it to last about one hour, at most.
Great interview by Unherd. Compare UK, Germany with Israel & Egypt on 5 June 21:
UK……………40,261 dead…..=593 deaths/mill……Pop:67,861,743
Germany……8,763 dead……=105 deaths/mill……Pop:83,765,996
Israel…………291 dead………=32 deaths/mill……….Pop:9,197,590
Egypt………..1,166 dead……=11 deaths/mill………Pop:102,189,071
Would Prof Fiston please add the number of hours of sunshine/y/country to his modelling. Hours of sunshine per year per country is the difference between Europe and Middle East in order to explain who could catch Covid-19 in their respective populations. Lower death rate is Egypt is due to her younger population compared with Israel.
Global data from: https://www.worldometers.info/coronavirus/#countries
This academic paper explains the ‘dark matter’ term used in this interview with Prof Friston:
From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health
https://academic.oup.com/aj…
People who get severe COVID-19 symptoms, or who are killed by it, are actually harmed or killed by their body’s weakened and dysregulated (overly-aggressive, inflammatory) immune response. The greatest single cause of this is low vitamin D levels.
I wrote a detailed response concerning this to a BMJ article Inequality in our ethnic minorities: we must act before the next pandemic but it did not get past the Disqus-based moderation system. I want to write a similar response here, but am concerned that Unherd’s Disqus-based moderation system will flag it as spam, in part due to the numerous links it contains to research articles.
You can read what I wanted to write here: http://aminotheory.com/cv19… .
vitamin D, while being helpful, is not a cure OR a prophylaxis for covid-19.
We know that viruses spread a lot more easily from person to person in confined places. Are any of the scientists checking whether the very late imposition of lockdown caused more harm than good, in effect INCREASING the spread of the virus?
Huge masses of people were NOT placed in limited and confined areas – like sports arenas, restaurants and movie theaters — they weer told to limit movement and remain AT THEIR OWN DOMICILE.
My basic training in stats indicated this conclusion but this reality was never part of the ‘economic’ game.
The subject matter is very interesting and important – for why on earth can’t you state the key points at the beginning of the article?
And why can’t the author (and indeed the interviewer) get to the meat of the matter, and its significance – without all of this turgid padding and preliminaries, which will cause many readers to just give up: most of us haven’t got the time to wade through such stuff, unless we see key points stated clearly at the beginning, to motivate us to wade through the rest!
Time is pretty much all we have, and this information is amongst the most important to understand.
Numerous independent scientific studies have concluded that the true mortality rate of the Corona virus is around 0.02 – the same as seasonal flu.
All references to such studies have been systematically censored out of existence in the mass media.
You might start by asking why that has happened.
Perhaps you could give citations into the scientific literature — peer-reviewed or recognised preprint sites such as medrxiv — for these “numerous” scientific studies? Five would do. Oh, and did you mean to say 0.02%, rather than 0.02 which is 2%? The IFR for seasonal flu is more like 0.2%, so neither of those. Current estimates for Covid are around 1%.
The total number of deaths in New York city is currently reported to be about 0.2% of the entire population, and up to 0.6% is some areas, as I said a little earlier in this thread. Even if the entire population had been infected then the IFR there cannot logically be less than those figures. Presumably that point is addressed in the scientific studies you can point us to?
because they are notoriously inaccurate.
Having to have comments ‘approved’ by your censors makes me lose all interest in, and trust in, your publication.
Very informative. I find it astounding that people are now lauding Ferguson’s claim that had we locked down sooner the death rate would have been reduced by up to half! This guy is proven to be an u reliable prophet of doom and didn’t by the way stick to the lockdown rule which his statistics informed.
I maintain as indeed I heard Toby Young say today and as Peter Hitchens has said for months that the lockdown is unnecessary and will end up being a greater threat than the virus it was meant to control. There is no evidence, none which proves or even suggests that the lockdown has had any effect on controlling the spread of infection. Never before in history has a healthy population been placed under strict restrictions, akin to house arrest in order to fight a disease. Let’s call it what it is, insanity!
Sweden. Sweden. Sweden. Arkansas. New Mexico.
All locations subscribing to “unnecessary and totalitarian” control of populations, after rescinding lockdowns, have seen a SIGNIFICANT rise in infections and deaths.
Are the people who think this is a hoax or a political ploy the same folks who think the moon landing was a fraud and the earth is really flat?
I KNOW THIS IS VERY IMPORTANT INFORMATION AND THE SPEAKERS ARE CLEARLY VERY SMART – THE PROFESSOR FOR FIGURING IT OUT AND THE INTERVIEWER FOR BEING ABLE TO GRASP IT, HOWEVER, THE WAY THIS IS PRESENTED IS NOT GOING TO HAVE THE IMPACT IT SHOULD. THIS IS VERY FRAGMENTED, AND CIRCUMSPECT, AND NOT PRACTICAL, OR USED TO RELATE TO ACTUAL EXAMPLES OR WAYS OF APPLYING IT. IT HAS POTENTIAL BUT IT REALLY NEEDS TO GET REAL FEEDBACK FROM PEOPLE WHO WATCH AND READ IT TO SEE HOW THE IMPACT COULD BE IMPROVED – AS IT IS NOW, I HESITATE TO COPY OUT TO MY NETWORKS BECAUSE I THINK IT WILL NOT HIT THE MARK.
Then restate it, yourself, to your “network”. (and try to NOT use CAPS)
It would explain why family members, who have had protracted exposure to an infected person, have not been affected. For example my wife, and 2 of my children and their children who all have a partner who has tested positive for Covid19 antibodies; me and 2 sons-in-law.
stay vigilant, and report back.
When science discovers a discontinuity between what is expected and what is
found, one immediate reaction is to identify the discrepancy as something novel — Mercury’s orbit anomalies indicated a hidden planet, or calculated gravitational force of galaxies do not account for their rotational velocity, an influence ascribed to “dark matter”.
The invisible planet altering Mercury’s orbit was removed by applying
Einstein’s rules of General Relativity. The cosmological bête noire “dark matter” remains to be explained, but Friston’s “dark matter” of immunity (or non-susceptibility) may have a simpler explanation offered by Derek Groen:
“Friston’s generative model omits more than 90% of the locations relevant for studying transmission of the disease, such as schools, supermarkets, parks and nightclubs. Instead, in his model people are either at home, at work, in a critical care unit or in a morgue.”
— Derek Groen, 4 June 2020, Lecturer in Simulation and Modelling, Brunel University London, builds computer-simulation models of cosmological dark matter as well as covid-19 modeling.
https://theconversation.com…
I want to personally thank Freddie Sayers for his series of “Lockdown TV” interviews; these helped me stay sane during the lockdown. Likewise the series “Perspectives on the Pandemic,” which early in the “pandemic” featured interviews with Stanford University scientists using real science to refute the official fear narrative. In retrospect the work Sayers and Co. are doing will be seen as the REAL journalism.
Half the population has fallen ill and died – “bring out your dead!”. The economy is deeply damaged and people everywhere are losing their jobs and livelihoods – a catastrophe. Darn that bubonic plague analogue.
Except the first and last sentences are not true are they Mr Johnson? I think you should go.