> [T]his paper shows that these patients still have (17 years later!) a robust T-cell response to the original SARS coronavirus’s N protein, which extends an earlier report of such responses going out to 11 years. This new work finds that these cross-react with the new SARS CoV-2 N protein as well. This makes one think, as many have been wondering, that T-cell driven immunity is perhaps the way to reconcile the apparent paradox between (1) antibody responses that seem to be dropping week by week in convalescent patients but (2) few (if any) reliable reports of actual re-infection. That would be good news indeed.
Yep, and I remember when I got my first kindle e-ink reader, the first one they made, and was in awe because between that and the first iphone a few months earlier, it reminded me so much of the device described in Neal Stephenson's Diamond Age.
I got used to it, and the feeling went away.
I had a similar feeling when I got a bluetooth headset where I just had to tap and speak and Google would answer almost any question I had, no need to even half shout "OKAY GOOGLE" for my phone to hear. I now actually feel dumber without such a headset because I can't easily get answers to random questions.
So, yeah, we get used to these things. The measure of "being in the future" is less the awe we have at technological marvels and more the way they become common place and accepted.
This cell transfer thing is just like a vaccination, but better. And a 2020 car is just like an 1820 train, but better. And a computer is just a programmable loom, but better.
Haha, I was with you until the computer comparison. A 2020 car can go an order of magnitude faster than a 1820 train. A 2020 computer can go so much faster I can't even estimate how many orders of magnitude with certainty.
Happens 1 in 100k people every year. It's called Guillain-Barré syndrome [1]. After an infection your immune system gets confused and starts attacking your peripheral nerves.
Yes, of course there are tons of autoimmune diseases (from mild allergies, to lupus, multiple sclerosis, and sympathetic ophthalmia), but Guillain-Barré syndrome is an autoimmune disease that's known to occur after otherwise banal infections or even vaccine shots. That's why I considered it more relevant to the OP than other autoimmune diseases.
I'm not familiar with what T cells do, I thought they did not have a single target, unlike antibodies -- wouldn't transplanting T cells mean they would immediately attack the patients cells, as they are detected as foreign?
T cells have a single target, like antibodies. The target is a peptide, a fragment of a protein 8-11 residues long. That peptide could show up in several target proteins, but usually (?) is unique to one protein.
This is a bit of an oversimplification. Firstly, the peptide is 8-11 residues for cytotoxic, aka killer, T cells which i think is what we're talking about here. It's 13-17 residues for for helper T cells. Secondly, there are varieties of T cells which don't have a single target, like invariant natural killer T cells, but those are pretty obscure, and not what people are talking about when they just say "T cells".
> The dust cloud is bringing dangerously high levels of fine particulate pollution (PM2.5, particles less than 2.5 microns or 0.0001 inch in diameter) and PM10 (particles less than 10 microns in diameter). Air pollution aggravates COVID-19 symptoms, leading to expected increases in hospital admissions from the disease in regions where dust concentrations spike.
We don't yet have good data to correct for the health impact of breathing in these minute particles from Africa, especially for those with pre-existing conditions.
"The paper speculated that this might be due to cross-reactivity with proteins from the “common cold” coronaviruses”, and raised the possibility that there might be a part of the population that has at least some existing protection against the current pandemic."
...this might explain why different parts of the world (e.g. east Asia, including Australia and New Zealand, vs. western Europe) have vastly different outcomes that don't seem to correlate well to genetics, culture, or policy. If a "common cold" coronavirus hit east Asia in the past, but never made it to western Europe, it could explain the different impact.
New Zealand is different because it eliminated the virus.
By April the infection had been isolated and through May they basically ensured the few people who had it were kept away from everybody else long enough to recover, by June they were finished and getting back to normal. Every new reported infection in New Zealand for the last 70+ days is a person in quarantine or "managed isolation" because they arrived from somewhere it's endemic. Will it leak eventually? Probably, and they're ready for that. [Edited to remove claim that New Zealand is unique when several other countries also eliminated this virus as pointed out by another poster]
They hoped Australia could do the same, and then they'd open the border to Australia, but Australia botched it and now has a high rate of new infections.
New South Wales has elevated case levels. It's not as obviously terrible as Victoria but it's going the wrong direction.
I actually didn't know about Vietnam and Thailand, so thanks for that. But again it seems like elimination was a conscious strategy like in New Zealand. So in my opinion strategy is the difference, not some innate biological quirk shared by people across New Zealand and Vietnam but apparently not in parts of Australia.
NSW has received cases from the Victoria bungle. There's little regard for social distancing or shut down measures. We're screwed now. It's just a matter of time.
If NZ is because it eliminated the virus, then it will all happen again when (inevitably, in a virus this widespread throughout the world) someone brings it back in.
Yes, unlike prior to the pandemic New Zealand is burdened by now requiring border controls to prevent re-infection and a test & trace infrastructure to find anything that slips past and stop community transmission.
All this is of course still much cheaper than the alternative.
The virus spread quite well in Wuhan and the South Korean church though. Why do you dismiss the significant policy differences as a sufficient explanation?
It fails to explain why countries like Vietnam, the Philippines and Indonesia have so few deaths.
There are 470 million people between those three Asian nations, and fewer deaths than in Canada (which has done a very sound job against the virus).
Indonesia has as many deaths as Sweden, with ~26 times the population. The Philippines has 1,846 deaths vs Brazil which has 82,771. Bangladesh has 2,751 deaths, 30% of what Germany has, despite Bangladesh having nearly twice as many people. The Germans responded in extraordinary fashion to the virus. Bangladesh has so few deaths because their response was vastly superior, better funded, better organized, technologically superior in its testing and tracing? Comeon.
The Philippines had an amazing response to the virus compared to Germany or Canada or Brazil or Switzerland? No way. There's definitely more going on there, including an impact from the different climates. It's entirely reasonable that some parts of Asia could have greater immune protection due to past virus exposures.
> It fails to explain why countries like Vietnam, the Philippines and Indonesia have so few deaths.
It's obvious if you check the population pyramids (Google "population pyramid $COUNTRY_NAME"). Most of the deaths are in the older population, and the average population age of Vietnam, the Philippines and Indonesia is much younger than e.g. Canada.
The data reported across certain countries may not be directly comparable due to differences in testing, reporting processes and other discrepancies.
Most of my asian friends believe mask wearing and willingness to self isolate (sick, so stay home/wear mask/try not to spread) are a factor when comparing to western nations.
Vitamin D may also play a part. I recall there were studies indicating that Vitamin D deficiency could be a problem for those who get sick. I have no data here but I suspect westerners are far more likely to be Vitamin D deficient.
I would not be surprised as well if general health across populations has a relationship (diabetes, obesity etc).
Aside from that, regulation and enforcement matter. Australia kept cases under control early on but their recent delay in locking down hard with new cases has meant the spread continues out of control. New Zealand on the other hand had a very strong lockdown and try to enforce quarantine and case management. So far cases are controlled and limited only to those returning from overseas. Community spread was eliminated (to date).
Becausr none of these countriest are telling you corrent mortality number. There are openly fuzzing the numbers and actively suppresing domestic jounalists with laws that protects the government from criticisms. This is atleast true for Bangladesh (where I am from), India, philipines and vietnam. To the best of my knowledge. There is absolutely no reason to believe that something magical is happening in this part of world. People are dying, infection rate extemely high. They are being highly under-reported.
Let's leave Vietnam out of this. They're not hiding their numbers. It's difficult for the rest of the world to admit this, but Vietnam beat the virus because their leadership acted quickly, ruthlessly and over time.
In the early days of the outbreak Vietnam didn't have rigorous contact tracing setup, so if a case turned out positive they simply shut down the entire neighborhood for two weeks. Once the source was mostly international cases, they also shut their borders and made no exceptions, not even for trading partners begging to let a handful of people in. But most importantly, even when case numbers went down into single digits, they kept up total lockdown for an additional two weeks.
This saved them from making the mistake Korea made in removing social distancing restrictions the day before a major 5 day weekend which seeded the country and we've been squashing spot fires here ever since.
Authoritarian regimes that have earned public trust through effective governance are probably the countries best suited to manage a pandemic like this one. It's just there are very few of them so it's hard to think of such countries as a category.
But none of that would matter, given that there are millions of people on the planet who have it, and they will continually get reinfected. Whereas, a previous cold virus that gave some significant portion of them immunity, would matter.
Also, South Korea's death numbers (and Vietnam's) both look pretty good compared to any nation in western Europe.
> Indonesia has as many deaths as Sweden, with ~26 times the population.
Indonesia's deaths are still rising (about to pass 100/day), while Sweden's have tapered off (has been below 20/day for a month and is still dropping).
> Bangladesh has 2,751 deaths, 30% of what Germany has, despite Bangladesh having nearly twice as many people.
Similar here: Bangladesh's deaths are stable (not really increasing or decreasing) at around 40/day, while Germany has tapered off to like 5/day for a month (and recently had days with 0 deaths).
Philippines vs Brazil seems to have a pattern that supports what you're working from, though - deaths in the Philippines haven't really spiked (aside from two recent days, not yet enough to know if it's an outlier or not).
"Bangladesh has so few deaths because their response was vastly superior, better funded, better organized, technologically superior in its testing and tracing? Comeon."
Take into account that beating this virus through contact tracing and isolation doesn't require having the fanciest tech. The actual steps are really simple.
Germany is wealthy enough that it doesn't have an infectious disease response "machine" on standby at every level, Bangladesh is not. Bangladeshi public health teams deal with outbreaks of deadly infectious disease all the time, that's not true in any wealthy country.
I don't doubt that if you gave each country five years, Germany would come up with a better funded, equipped (and maybe even trained) public health system but this was a situation where days mattered.
It would be quite a coincidence if Australia, New Zealand, Japan, South Korea, and Vietnam all just had different reasons for having lower death totals (by a LOT) per capita than all the nations of western Europe. An explanation that didn't require a different explanation for every nation in east Asia is a lot more convincing, I think.
Actual scientists i follow on Twitter are consistent in saying there is no sign of strains with different virulence. I believe this is a myth. I would be interested to see any actual research showing otherwise, if you can find it (not NYT articles!).
There's a more infectious mutation that overtakes the original form wherever it spreads, including Asia, although it's not more severe. I guess Asian countries would have an advantage because they faced the original form first and got their act together, while Europe and the East Coast of the US faced the more infectious variant early on. (The West Coast, on the other hand, started out with the original form, probably because the virus came directly from Asia. The variant didn't even show up in the Bay Area until May, for example.)
> The D614G mutation displays only three independent emergences that qualify for inclusion in our analyses. While this limits our power to detect a statistically significant association with transmissibility, the low number of recurrent mutations leading to the D614G allele suggests that, rather than being a driver a of transmission itself, it arose early and went up in frequency by hitchhiking with one of the deepest branches in the global phylogeny as the SARS-CoV-2 population expanded.
People are still working on this, and it should become clearer in time.
Do you really find it easier to explain the different impact with genetic differences rather than simply different government policies and cultures? What about it doesn't correlate again?
I think it's hygiene related. I hypothesize that people living in countries with low hygiene have more exposure to diseases and thus better immunity. Examine India:
In India, People throw trash everywhere, defecate everywhere, piss everywhere, wipe their rear ends with their hands, eat with their hands, and also shake other peoples' hands with the same hands... In general, it's well known that India is a pretty low hygienic country. Which may explain this:
Basically low hygiene exposes people to more diseases allowing their bodies to develop greater immunity inline with the quotation you mentioned above.
There may be a correlation. I just gave some anecdotal data... Maybe some data scientist can find the correlation between two quantitative datasets: quantitative hygiene levels by country and deaths/infections of covid-19 by country.
Data in India has a long way to travel from village to town to district to state to the national level. At each stage all kind of errors intentional and unintentional enter the system. All these errors keep accumulating as they move up the food chain. By the time it reaches the top (and it takes its sweet time) god knows what it actually means.
Just to make things more interesting there is major fudging at the end of the chain to make it fit what was produced by the system over the previous years, cause budgets and all kinds of plans and policies that are based on prior garbage will start imploding otherwise.
The interesting thing Covid has done is expose how bad those numbers are because the regional govts for the first time are dutifully releasing Daily Data from the morgues. That data leaks out non-covid deaths, which should more or less match non-covid deaths/mortality rate data reported from prior years. And it doesn't. By large factors.
(Google non covid mortality rate for whatever city and compare with historic numbers in the national data portal)
Your hypothesis assumes they are all not dying from low hygiene. They probably are, in large numbers, and are just not being counted.
I haven't even presented data, I just presented a hypothesis using a BBC article about India as an anecdotal example.
The article is literally from the BBC. You are literally saying the BBC is completely wrong about India. If that's the case then really the onus of proof is on you. Why should I trust the arbitrary words of some guy on the internet over the BBC? I mean I don't even completely trust the BBC but I trust you even less.
All the stuff you wrote could be pulled out of your ass. Just reference your sources about inaccurate covid data from India if you want me to believe you, which I will if you provide at the very least a source that has equal weight to my own source... Like I'll even take Fox news as evidence enough to dispute the veracity of BBC.
>Your hypothesis assumes they are all not dying from low hygiene. They probably are, in large numbers, and are just not being counted.
I mean isn't what you just said just another hypothesis? Worth considering. The same quantitative analysis done on my suggestion will say something about your hypothesis as well. Either way worth looking into.
I mean, we're just talking about India here, my hypothesis extends past India. I can use other anecdotal data for comparison...
The country with the lowest hygiene index is Ethiopia. Total corona virus deaths: 167. That's a small, small amount. You say shitty data as well? I say, it could be, but low hygiene needs to be investigated as this is what the OP's comment is suggesting.
So Obviously, it it Evidence? No. Worth looking into? Yes.
> low hygiene exposes people to more diseases allowing their bodies to develop greater immunity
Interesting theory, and I asked an epidemiologists that very question ("is it better to expose yourself to everything or to be hygienic?"). Her answer: it's complicated.
If there is a nearly harmless coronavirus going around, whether it is a common cold or previously unidentified virus (as the article suggests), that provides partial immunity to COVID, what is stopping us from purposefully infecting people with a less harmful illness to protect from COVID? Isn’t this how the first idea of vaccines came about with Cowpox and smallpox?
1. Actually finding, isolating, and harvesting that virus, and
2. Proving that getting that virus doesn't cause some form of immune enhancement syndrome that would cause subsequent infection by a different coronavirus strain to result in more severe symptoms. (e.g., getting infected with one strain of Dengue fever causes lifelong immunity to that strain, but it also typically results in far more severe symptoms if you then catch a different strain). Immune system issues were identified with some earlier SARS vaccines but researchers discovered a likely way around it.
Definitely too far if handled by government, but if the possibility exists as individual choices, some people would definitely go for it. Chickenpox parties are a thing, after all.
i'm not saying "modern medical ethics" is a good thing in this case (though I think some line is obviously essential to protect the rights of the individual in the face of abuse to cure the many) but that the formal and informal accords of the medical community that constitute that system of ethics is the reason no one (except maybe an authoritarian regime with no concern for individual liberties cough xinjiang) is talking about infecting healthy people to test vaccines or build up herd immunity.
This. Nothing stops us from doing this. Creating an attenuated virus vaccine or stumbling across one in nature is just two different ways of getting the same thing.
Once you have it, you still need to do the long 3-phase approval that normally takes many years (and now takes perhaps 9-18 months because it’s an emergency). But it’s still a vaccine.
The question perhaps is could we stop people from having their own “parties” with people identified to have the less dangerous immunity-causing virus? Probably not. I wouldn’t go to one though.
That's literally how herd immunity works. People with no or mild symptoms go out and spread the virus, people with heavy symptoms stay home. Virus is encouraged evolutionarily to be as non-symptomatic as possible.
Unfortunately we have totally broken this with our lockdown strategy, which has meant that heavily symptomatic people are allowed out to get medical treatment and spread the virus in clinic and hospitals, whilst everyone else is forced to stay home.
At the end of May, however, an immunological study by the University of Zurich was published, which for the first time showed that the usual antibody tests that measure antibodies in the blood (IgG and IgM) can detect at most about one fifth of all coronavirus infections.
At the same time, the Swiss study may explain why children usually develop no symptoms (due to frequent contact with previous corona cold viruses), and why even hotspots such as New York City found an antibody prevalence (IgG/IgM) of at most 20% – as this already corresponds to herd immunity.
The Swiss study has in the meantime been confirmed by several more studies:
A Swedish study showed that people with mild or asymptomatic disease often neutralized the virus with T-cells without the need to produce antibodies. Overall, T-cell immunity was about twice as common as antibody immunity.
A large Spanish antibody study published in Lancet showed that less than 20% of symptomatic people and about 2% of asymptomatic people had IgG antibodies.
A German study (preprint) showed that 81% of the people who had not yet had contact with the new corona virus already had cross-reactive T-cells and thus a certain background immunity (due to contact with previous corona cold viruses).
A Chinese study in the journal Nature showed that in 40% of asymptomatic persons and in 12.9% of symptomatic persons no IgG antibodies are detectable after the recovery phase.
Another Chinese study with almost 25,000 clinic employees in Wuhan showed that at most one fifth of the presumably infected employees had IgG antibodies (press article).
A small French study (preprint) showed that six of eight infected family members of Covid patients developed a temporary T-cell immunity without antibodies.
1. Dozens of localities have controlled the virus via lockdowns, social distancing and masking, they all show similar curves to NY but with lower peaks. NY therefore offers no evidence that herd immunity has been reached.
2. Your Spanish study shows 90% of those with a positive PCR test also had antibodies. The low symptomatic positive rate could be easily explained by other seasonal illnesses with identical symptoms.
3. There is no evidence beyond supposition that I can see for the Wuhan clinical workers having the virus. An alternative explanation is that protective equipment and protocols were effective.
4. The idea of 80% of the population being T-cell immune seems inconsistent with the outcomes on the Diamond Princess.
I think you are cherry-picking data to support a far-fetched theory. The outcomes in confined places where the virus infects everyone, like the Diamond Princess or nursing homes, seem especially hard to square with the idea of widespread t-cell immunity.
Edit: I was misremembering the Diamond Princess, not everyone on the cruise ship got the virus. However, Marion Correctional Institute in Ohio had 80% test positive for covid; the Life Care Center in Kirkland, Washington had 2/3 test positive. These don't seem consistent with widespread T-cell immunity.
Interesting you mention the Diamond Princess, it actually supports the "far-fetched" theory. And it's not as far fetched as you think, it's gaining more ground and does explain places like New York, London, Sweden, India etc.
"In the accidental experiment of the Diamond Princess – a close community where the infection was allowed to spread unchecked for a fortnight in January, and everyone was eventually tested – only 17 per cent of passengers and crew became infected."
New York (and similar UK and Sweden) has a higher death rate since they moved sick patients into care homes and decimated them. As you said everywhere saw similar curves no matter how strict or lax a lock down they had. Implying something else is going on and not the lock down.
“full lockdowns and wide-spread COVID19 testing were not associated with reductions in the number of critical cases or overall mortality.”
So, to me at least, it does seem far more plausible that t-cells are more a mitigating factor then lock downs.
If I am cherry picking, seems to be lots of cherry trees to pick from.
I see no reason why t-cell should not offer some protection, like it does with other coronaviruses. And why we would assume that everyone is just as susceptible when we know the risk profile varies wildly.
EDIT: for your explaining your edit of "Life Care Center in Kirkland", the reason they have more antibodies is that we all know the older you get the less t-cell protection you have. A "life care" center one assumes is full of old people, hence lower t-cell protection. And it explains why children have more protection as their t-cell protection is stronger.
Everywhere saw a similar shape of curve, i.e. exponential increase until the lockdown, then slow exponential decrease. The peak of the curve differed widely, and countries that were slow to lock down like the UK, Sweden and USA have seen some of the worst outcomes.
Correlating lockdown policy to outcome does not make sense because lockdowns are instituted in response to case levels in the first place. It is like correlating fire trucks and fires, and finding that fire trucks cause fires because there are more of them in dry, fire-prone areas.
Sweden provides something close to a natural experiment, it has similar culture and climate to its neighbors but a far worse outcome after it did not lock down.
Prisons are not especially weighted toward older people and they have seen outbreaks with as many as 80% being infected.
You just ignored the science in front of you and assumed countries like Sweden was because of the lock downs. When the maths doesn't add up. I don't think you even read my comment nor the paper as I didn't mention cases but mortality. If lock down is a reactionary process to cases then the different types of lock down should change the mortality.
Sweden, New York and UK are easily explained if look at the age range and location of deaths. It was the reaction of sending sick patients out to care homes.
Bringing up Sweden, you just cherry picked only it's Nordic neighbours, but it compares quite well, and normal, with the other European countries. If you look at the previous flu seasons for the Nordic countries you will see that Sweden had a few years of very low deaths, whilst the countries you cherry picked had a few years of high death. So Sweden's care homes were packed with more vulnerable people.
Prisons also further support the t-cell theory. People in prison don't get enough sunlight and vitamin-D, reducing their t-cell immunity. Also they are heavily weighted towards minorities who are more susceptible.
And since coronovirus are quite seasonal usually, and t-cell response changes with season, it's why we are seeing different cycles for the northern hemisphere, the southern hemisphere and the equatorial regions. USA is a big country, the northern states got hit first and now the southern states are matching the regions like Mexico. USA is so big you need to treat each state like it's own region and not generalise.
curious who wins the vaccine race. my understanding is the RNA vaccines being researched by Moderna and Inovio don’t stimulate T-cell development, in which case they seem like poor candidates compared to the adenovirus candidates like the Oxford one that do.
Good T-cell response has historically come from replication competent virus (live virus vaccine) because the process of replicating their genetic material and producing proteins triggers many of the T-cell responses. Inactivated virus vaccines or protein sub-unit vaccines require adjuvants to trigger these mechanisms and have never given protection as good as live virus.
mRNA and viral vector (which are the leading approaches right now) are very new and try to produce the effect of live virus vaccine without having to first find an attenuated, stable vaccine strain. They do this by using either another virus or a lipid shell to inject genetic material into cells which starts the cells producing proteins.
I would expect both the Moderna and the Oxford vaccine to give some T-cell immunity as well as antibodies.
so mRNA vaccination is an offshoot towards technology which was created about a decade and a half ago to make more efficient monoclonal antibodies for the lab. The process is to extract B-cells from a challenged organism (almost always mouse) and then fuse them as 'hybridomas' with immortal cancer cells, select single cell clumps that show an immune response out of multi-well plates, and then use those immortalized cells to make that one antibody forever.
So indeed the mRNA vaccines come from technology that is highly optimized to elicit a B-cell response. (Not to say that it doesn't stimulate T-cells, but I wouldn't be surprised if it didn't).
Wait I’m a little confused. It seems like injecting people with an mRNA, which their cells then translate into an antigen that provokes an immune response, is a very different technology from monoclonal antibodies. They are both related to the immune system, but mRNA vaccines are at least partially about stimulating polyclonal antibody production, as opposed to monoclonal antibodies. Can you articulate why you think mRNA vaccines were derived from monoclonal antibody work?
I just remember talks (I was at a cutting-edge immunology research center, The Scripps Research Institute in San Diego) about using mRNA vaccination in the 2007-2009 era to make monoclonal antibodies. Oddly, I can't find any publications from that era on it (but I can find a few papers from 2017-2019 using that exact methodology), so it appears that either i was mistaken, or it quietly pivoted to human vaccination as a target. Setting aside the veracity of my memory, (assuming I'm not hallucinating) It's really not possible for me to be mistaken about the timeframe, though, since I have been out of biology since 2015.
This is very confused. The hybridoma process you describe is the only way to make monoclonal antibodies, not a more efficient way, and it was invented in the early 1970s. It has nothing to do with mRNA vaccines.
Both mRNA vaccines so far have produced T-cell responses with Pfizer/BioNTech producing more CD8 than Moderna. Both had detectable levels of responses, though. As is typical in clinical development, we need to wait for the phase 3 data before making a decision.
