|
Cross Immunity, Nicotine Patches And Other New Covid-19 Science
Good news!
There is some cross immunity between a viral common cold and Covid-19.
T cells found in COVID-19 patients ‘bode well’ for long-term immunity – Science
Immune warriors known as T cells help us fight some viruses, but their importance for battling SARS-CoV-2, the virus that causes COVID-19, has been unclear. Now, two studies reveal infected people harbor T cells that target the virus—and may help them recover. Both studies also found some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses.
The last half sentence is really, really good news. People who previously had an infection caused by one of the four known common cold coronaviruses have developed some capability to also fight the SARS-CoV-2 coronavirus. This must have already changed the way the pandemic developed. Had there not been this protection in parts of the population there would have been more Covid-19 cases and likely many more severe ones.
That some people already had some grade of immunity might also explain the two limited outbreaks on cruise ships that only hit a third to half of the passengers and crew. Without partial previous immunity more people on those ships would likely have fallen ill.
The two studies mentioned in the Science report are:
Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals
– Cell
Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.
and
Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors – medRxiv
We demonstrate the presence of S-reactive CD4+ T cells in 83% of COVID-19 patients, as well as in 34% of SARS-CoV-2 seronegative healthy donors, albeit at lower frequencies.
The T-cells generated during a Covid-19 infection are more specific to the SARS-CoV-2 virus than the T-cells generated to fight off a normal virus common cold. But a human who has recently had a virus induced common cold will have an immediate but imperfect immune reaction to a SARS-CoV-2 attack while those without such protection will lose critical time as they must build up the immune reaction from scratch while the viruses continue to multiply.
Since the Science report appeared a third study was published that detected a similar result for antibodies:
Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans – bioRxiv
Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 Spike (S) glycoprotein, we demonstrate the presence of pre-existing immunity in uninfected and unexposed humans to the new coronavirus.
—
The rise and fall of hydroxychloroquine:
Utah went all-in on an unproven Covid-19 treatment, then scrambled to course-correct – STAT
The saga of the drugs’ rise and fall in Utah, pieced together from documents STAT obtained through a public records request, provides a case study of what happens when hope and excitement about therapies outpace the evidence.
Two recently published studies provide that hydroxychloroquine does not help in mild or medium Covid-19 cases but has severe side effects in about 10% of the cases in which it is used.
Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial – BMJ
Conclusions Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion [i.e. release from hospital] than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients.
Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data – BMJ
Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment. …
[T]he results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.
—
After reports from China that active smoker representation in severe cases of Covid-19 was less than expected a French researcher suggested a mechanism by which nicotine potentially hinders the virus replication. A trial with nicotine patches was started in France and another one is planed in the UK.
New data suggests that it is not the severity of the disease that differs in current smokers from others but that their risk of getting infected at all is much lower than for non-smokers. From a Lancet comment: Who is most likely to be infected with SARS-CoV-2?
Among chronic comorbidities examined, only those with chronic kidney disease had an increased risk of infection, whereas the risk in active smokers was around half that observed in never smokers.
A large data study from Britain about the progression of the disease supports that:
OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. – medRxiv
We found some evidence of increased risks in former smokers. In current smokers there was a slight protective effect, which was removed when fully adjusted for ethnicity. The risks associated with smoking have been disputed, with increased risks initially reported, but some more recent reports finding that smokers are under-represented in those with more severe disease, and a potential protective mechanism for nicotine has been suggested: smoking prevalence was lower than expected among hospitalised patients in China, France and the USA. Even if smoking does have a small protective effects against COVID-19, this would still be massively outweighed by the well-established adverse health effects of smoking.
—
The Economist has compared 'excess deaths' statistics for various countries. It has now published the raw data and the software its used to process them at Github:
The Economist's tracker for covid-19 excess deaths
New York State governor Andrew Cuomo was much lauded for his reaction to the epidemic. But a more detailed look and a comparison to California paints a much darker picture:
Two Coasts. One Virus. How New York Suffered Nearly 10 Times the Number of Deaths as California. – Pro Publica
The reopening after the lockdown is not happening as it should happen:
Failing the Test — The Tragic Data Gap Undermining the U.S. Pandemic Response – NEJM
Reopening state economies without the precision provided by analysis of rigorously reported testing data seems a peculiarly American form of madness.
There Are Sensible Ways to Reopen a Country. Then There's America's Approach – Time
One of the severe economic consequences of the epidemic:
The next phase of America's coronavirus problem is a massive housing crisis – The Week
A reminder to keep the masks up:
Coronavirus: hamster research shows effectiveness of masks ‘huge’ in Covid-19 battle, Hong Kong scientists say – SCMP
The study, which the team called the first of its kind, found the rate of non-contact transmission – in which the virus was transmitted via respiratory droplets or airborne particles – dropped by as much as 75 per cent when masks were present.
Last but not least a must read:
Profiting from Coronavirus – Craig Murray
—
Some have criticized the current restrictive comment policy on coronavirus threads at Moon of Alabama. Others have explicitly lauded it. It will continue.
Comments that give dubious medical advice or hype this or that unproven remedy will be deleted. Those who insist on reposting such comments will get banned. There is already enough misinformation out there and it does not need further amplification.
But with regard to anecdotal/unverified [touch’e] claims of nicotine benefits in covid, one should not reflexively ignore the evidence to the contrary that conflict with one’s pro-nicotine bias/belief system:}
“Smokers more likely to express ACE2 protein that SARS-COV-2 uses to enter human cells”
“Tobacco smoking increases lung entry points for COVID-19 virus”
Posted by: gm | May 19 2020 16:13 utc | 129
Touché again gm!
It is indeed desperate grasping at straws to believe that smoking will protect against Covid-19 when far higher quality research clearly indicates increased risk from smoking that the disease will be more severe (the latter also being the more plausible result).
As I commented the last time B raised this issue, there is one genuine effect of a past history of smoking that statistically reduces risk of death from Covid-19 – namely smoking significantly reduces expected lifespan, and therefore reduces the risk of living long enough to reach the highest risk age groups for severe Covid-19. Alternatively expressed – smoking kills you off first before you get a chance to be killed by Covid, if that is what you want. Post-hoc nicotine patches at a late stage deny you even that advantage.
There are some who parrot Big Pharma vested interests in ridiculing and denigrating hydroxychloroquine, despite the very notable positive results several countries such as China, Russia, Iran and Turkey have had with it, while vainly spouting the benefits of smoking despite complete lack of quality research papers supporting it and abundant quality papers against.
At this point it is worth reminding of criticism of the untrustworthiness of modern medical science from the editors of some of the top medical journals:
Skeptical of medical science reports?
“It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as editor of The New England Journal of Medicine”
Angell M. Drug Companies & Doctors: A Story of Corruption. The New York Review of Books magazine.
More recently, Richard Horton, editor of The Lancet, wrote that “The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness”
Horton R. Offline: What is medicine’s 5 sigma? http://www.thelancet.com.
The first of these two commentaries on clinical research publications appeared in 2009, the second in April of this year. These statements are being taken seriously, coming as they do from the experiences of editors of two of the world’s most prestigious medical journals. The first article showed how the relationships between pharmaceutical companies and academic physicians at prestigious universities impacted certain drug-related publications and the marketing of prescription drugs. Potential conflicts of interest seemed to abound: millions of dollars in consulting and speaking fees to physicians who promoted specific drugs, public research dollars being used by a researcher to test a drug owned by a company in which the researcher held millions of dollars in shares, failure of university researchers to disclose income from drug companies, company subsidies to physician continuing education, publishing practice guidelines involving drugs in which the authors have a financial interest, using influential physicians to promote drugs for unapproved uses, bias in favor of a product coming from failure to publish negative results and repeated publication of positive results in different forms. The author, Marcia Angell, cited the case of a drug giant that had to agree to settle charges that it deliberately withheld evidence that its top-selling anti-depressant was ineffective and could be harmful to certain age groups.
…
Richard Horton’s statement was part of his comments on a recent symposium on reliability and reproducibility of research in the biomedical sciences and addresses a broader area of concern. Some of the problems he identified are seen in the veterinary literature. They include inadequate number of subjects in the study, poor study design, and potential conflicts of interest. He notes that the quest for journal impact factor is fuelling competition for publication in a few high reputation journals. He warns that “our love of ‘significance’ pollutes the literature with many a statistical fairy-tale” …
Research is not created equal. There is good research (some, not so much) and there is bad research (bundles of it), mostly funded by vested interests, who where necessary direct the desired results. In general, research from China and Russia arguably tends to be higher quality and more reliable because those countries place the emphasis on health for society, not on profits for the corporations.
@Flatulus @16 “sources”
Christian Drosten, chief virologist Charité Berlin in his podcast no 31. Available with transcript here.
Posted by: b | May 18 2020 16:42 utc | 32
B, have you looked into the Big Pharma vested interests of Drosten yet? I suggest you do so.
Posted by: BM | May 20 2020 6:17 utc | 146
Interesting to see how the official fear propaganda on Covid has changed away from “it’s so infectious and deadly, it will be like the Spanish Flu, probably worse”. Most countries have no excess mortality at all (Germany – so far on a 3-year low, most of Europe), some a bit such as the UK where this flu is on par with the 5 strongest flus of the last 25 years, i.e. a 5-year event. Spiegelhalter in the BMJ (the heart of the UK medical establishment) just said two thirds of Covid-attributed deaths in the UK are in fact caused by the lockdown.
Posted by: Leser | May 20 2020 7:42 utc | 148
Indeed. But don’t forget the first phase before the panic porn phase! As China Started to suffer under the rapidly growing problem in early January and took decisive steps to bring it under control, the West, led by the US and UK psychopaths, were busy accusing China of “abusing human rights” with their “excessive” lockdowns, laughing off the seriousness of the disease, and making very little attempt to hide their glee at the predicament China faced.
Very important that people do not forget that first phase, as it is highly incriminating of Western governments – both with respect to their actions concerning Covid/China and with respect to their actions towards their own populations; even more so now as it becomes clear that they are forced to change their tactics again.
——
With respect to this, I found something very interesting and revealing in two papers, both of which were published earlier.
Phylogenetic network analysis of SARS-CoV-2 genomes (Forster et al)
In silico comparison of spike protein-ACE2 binding affinities across species;
significance for the possible origin of the SARS-CoV-2 virus (Piplani et al)
The Piplani paper measured the bonding energy of SARS-CoV-2 spike protein to ACE2 receptors in different kinds of animals, showing that in some (such as horse) the bond is rather weak, causing low infectivity and no overt disease. In the hamster or monkey the binding energy was considerably higher, reflecting much higher infectivity. What was striking, though, is that the binding energies to human ACE2 cells were the highest of all, while binding energy to bat ACE2 was considerably lower.
What this means is that SARS-CoV-2 (the virus causing Covid-19) is highly adapted to humans. This is despite the fact that the Piplani research was based on the earliest virus genomes from the beginning of the infection in Wuhan, i.e. supposedly before it had any chance to adapt to humans. Furthermore it supposedly came from bats, yet there is absolutely no sign of its presence in bats, no sign of a Covid-19 epidemic in bats, no sign that it was gradually evolving into SARS-CoV-2 in bats, and furthermore the binding energy to bat ACE2 cells is far too low. This is highly suggestive that the virus was developed in the laboratory.
Now consider the Forster paper, which discusses the evolution of the virus from the earliest samples found in Wuhan, and the mutations that spread around to different parts of the world in the early stage of the pandemic (it does not take into account the huge number of mutations that have occurred since then, nor of course the earliest versions recently shown to have been present in the US and Europe in November 2019 or earlier). It is based only on the 160 largely completely sequenced SARS-CoV-2 genomes in the GISAID database in early March 2020.
Forster described the early varieties of SARS-CoV-2 as falling in 3 main groups, A, B and C, with A being the “ancestral” group which was closest to the nearest known virus that has been found in bats, BatCoVRaTG13. The “ancestral” group A is also divided into 2 subclusters, the T-allele (closest to RaTG13) and the C-allele (not C group!!) which differs only by the T29095C mutation. Nearly half of this C-allele subcluster is found outside East Asia, mainly in the USA and Australia (this is before early March, remember; after that it would be far more complicated).
Then there are two groups derived derived from group A (specifically, from the C-allele of A). The first, group B, is derived directly from A. The second, group C, is derived in turn from Group B. Now here is where it gets interesting – and remember this is only genomes already sequenced by early March, so only cases in February or earlier.
Group B is derived from A by two mutations, one synonymous and one non-synonymous. All but 19 of the 93 B group samples came from East Asia, mainly China 10 cases in neighbouring countries of East Asia. Every single sample of the earliest form of B-group (i.e. with just 2 mutations from A-group) was found in East Asians, while every single sample of B-group found outside East Asia had additional mutations. Thus there is a very strong implication that B group (and presumably also A group, but that issue is not discussed by Forster since it is virtually monopolised in East Asia anyway) is genetically adapted specifically to East Asian ethnic group. Where B group has been found outside East Asia, it seems to have required further mutations to adapt it (still at this point being classed as B group) to non-East Asian ethnic groups. Forster et al state:
A complex founder scenario is one possibility, and a different explanation worth considering is that the ancestral Wuhan B-type virus is immunologically or environmentally adapted to a large section of the East Asian population, and may need to mutate to overcome resistance outside East Asia.
Group C is further derived from group B, and differs by a non-synonymous mutation G26144T. In the dataset it is predominantly in Europe, with samples in France, Italy, Sweden, England, California and Brazil. It is completely absent (in this database) from China, but 5 samples are found in Singapore, and some also in Hong Kong, Taiwan and South Korea (notably, all of which are much more internationalised than China).
—
Now, there is a further twist, with reference to the following paper:
Geographic and Genomic Distribution of SARS-CoV-2 mutations
This involved a study of 10014 different SARS-CoV-2 genomes that had been sequenced by 20th April 2020, and analysed the differences by continent, by country, and by group. By the time of this paper the knowledge of the virus had progressed, and the grouping is different: here the 10014 genomes are classified into three clades, according to the main gene involved in the branching, and are referred to as clades S, G and V. S corresponds roughly to Forster’s Group B, and G to Forster’s Group C. Clade S seems to include group A. I assume V is another group that developed subsequently to Forster’s paper, and I assume probably derived from clade G since it is found predominately in Europe.
Thus clade S is the ancestral group A/B that predominates in East Asia especially China. What differentiates clade G from clade S is the gene encoding the spike protein, which binds to the ACE2 receptor. In other words this is an adaptation to bind to Caucasian ACE2 receptors more effectively.
Furthermore, taking the earliest published genome (from Wuhan) as reference, the least divergence from this reference was found in the East Asian countries China, Hong Kong, Singapore and Japan, plus Iran [Iran, though, according to another source, was a distinctly different genome, evidently optimised for Iran] in other countries the divergence from this reference is much greater, apparently evidencing an evolution to adapt to different ACE2 receptors. Furthermore again, the paper notes that all the different countries of Europe had exactly the same profile of expression of the different genes, whereas the different countries of East Asia showed marked differentiation between each other, especially Japan.
In other words the original form of the virus released in Wuhan was specifically adapted to ethnic Chinese ACE2 receptors. This strain of the virus seems to have had some difficuty infecting Europeans, and when it did infect Europeans the infection was mild. Could this be the explanation for the extreme overconfidence of the West from January to mid-March? They expected that Caucasians would be less affected by the virus than the Chinese, unprepared for such rapid adaptation through mutation.
Here is my hypothesis: The US created this virus specifically to attack China. The genetic code of the spike protein was specifically designed to be optimised to attach to the Chinese ACE2 receptor. The form created by the USA would be the T-allele of Group A (the earliest known strain). Being artificial, it was genetically unstable, and quickly mutated after the start of the outbreak in Wuhan, first to the C-allele of Group A, then through two more mutations to the B Group, which was more stable for infections in ethnic Chinese – meaning, the virus is well adapted to attaching to Chinese ACE2 adaptors, therefore it does not need further selection to thrive in this ethnic group. This B group spread within East Asia, but could only thrive outside East Asia by further mutations – meaning that amongst millions of replications of the virus in non-Chinese hosts, those mutations that were better adapted to the non-Chinese ACE2 receptor would thrive better through natural selection. When B Group samples reached Europe, they quickly adapted to the new hosts through natural selection to attach better to the Caucasian form of the ACE2 receptor, giving rise to the new Group C (later classified as G clade). Thus, suddenly the virus became – contrary to US plans and expectations – well adapted to infecting Caucasian hosts. Thus, the strange delayed shock realisation that we have observed in Western politicians, especially British and American.
There are a couple of interesting predictions from this hypothesis, which can be tested if the relevant data eventually becomes available (I think it is bound to come out eventually). Firstly, my hypothesis is that the original strain leaked from Fort Detrick would have been the A Group (T-allele), which is not so well adapted to infecting Caucasians. This might be why it was relatively well contained before February. The US government, of course, would know this. After it escaped into the US community, though, it must have mutated. These random mutations would have been different from those which occurred in Wuhan, thus these mutations would all be different branches from A than those observed by Forster. If some of these early strains could be sequenced, they should be in this alternate branch – still derived from the ancestral Group A, but with quite separate development, as a distinct branch. This branch would have tried to adapt to Caucasian ACE2 receptors, but may have been more or less successful than Group C, and may have been both more or less infectious, and more or less fatal, than Group C. These mutations should be different from those found in China. There are many ethnic Chinese in the US military – did the US avoid including these ethnic Chinese in the Wuhan military games? What were the ethnicities of the 6 participants urgently evacuated from Wuhan during the games?
The second prediction concerns the early virus strains found in Europe in November or earlier. What type of strains were they? If they reulted from infections from the US team in Wuhan in October, they again must have mutated after reaching Europe, and they may have been yet another branch from Group A, with mutations different from both the US branches and the Forster branches. Alternatively, perhaps this was the origin of the C group – nevertheless this is less likely since C group is derived from B group, which according to this hypothesis should not have existed in Wuhan until after it spread amongst the Chinese. A third possibility is that the early European strains also came from the US leak, and started spreading – like the early US forms rather slowly – before the Wuhan games took place. In this case the early European branches should be derived from somewhere on the early US phylogenetic tree.
Posted by: BM | May 20 2020 16:35 utc | 156
|
