New Data on T Cells and the Coronavirus
blogs.sciencemag.org
blogs.sciencemag.org
Kramer writes in his pre-print that you’ve linked:
>Of note, our observations are in contrast to a recent report by Long et al. that found waning titers 8 weeks post
138 virus infection as compared to acute responses (19). Especially in asymptomatic cases, antibody
139 responses disappeared after 8 weeks in 40% of individuals in the Long et al. study. However, the
140 antibodies measured in their paper were targeting the NP plus a single linear spike epitope. Much
141 more in agreement with our data, the same paper also reports relatively stable (slightly declining)
142 neutralizing antibody titers. The stability of the antibody response over time might therefore also
143 depend on the target antigen. The titers we measure here do correlate with neutralization as
144 discussed above.
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.
I take your point, but what's sci-fi is always a receding horizon :)
AFAIK the hypothesis is that is a result of modern life being “too clean”, so not enough “unfriendly” variety to train on.
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.
...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.
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.
Also, Australia's botching is effectively contained to a single state (Victoria), which is sealed off from the rest of the country.
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.
All this is of course still much cheaper than the alternative.
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'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.
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).
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.
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).
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.
This research came out months ago but no one is mentioning this.
"Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus" https://www.cell.com/cell/pdf/S0092-8674(20)30820-5.pdf
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 news and views bit on that Cell paper puts it in context:
https://www.cell.com/cell/pdf/S0092-8674(20)30817-5.pdf
Another study didn't find an effect on transmission:
https://www.biorxiv.org/content/10.1101/2020.05.21.108506v4
> 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.
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:
https://www.bbc.com/news/world-asia-india-52435463
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...
Given this: https://www.indexmundi.com/facts/indicators/SH.STA.BASS.ZS/r...
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.
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.
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.
Test to find asymptomatic people and track outcomes to find very mild strains. Then spread it. Glossing over some points here, but that was the idea.
Something like will be illegal in (guessing) 4 separate ways.
It's too far outside too many boxes. Sit down!
You can also make a good argument for variolation. Which is to infect yourself with a small amount of viruses.
This will (ideally :) create a small infection that your immune system can beat off in time, and then you'll be immune after a minor time sick.
Apparently, people did this with smallpox in the pre vaccine era.
this is independent of the multitude of evidence that this is bad for non-hospitalized people too https://www.medscape.com/viewarticle/934851 https://news.berkeley.edu/2020/07/08/from-lung-scarring-to-h...
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.
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.
The exact same virus can give one person heavy symptoms and another person light symptoms.
The immune system plays a bigger part than the strain of virus.
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.
https://www.biorxiv.org/content/10.1101/2020.05.21.108308v1
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.
https://news.ki.se/immunity-to-covid-19-is-probably-higher-t...
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.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
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).
https://www.researchsquare.com/article/rs-35331/v1
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.
https://www.nature.com/articles/s41591-020-0965-6
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).
https://www.medrxiv.org/content/10.1101/2020.06.13.20130252v...
A small French study (preprint) showed that six of eight infected family members of Covid patients developed a temporary T-cell immunity without antibodies.
https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v...
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.
https://www.spectator.co.uk/article/immunity-to-coronavirus-...
"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.
Studies looking at the impacts of lock down on the curve are showing very little correlational https://www.thelancet.com/journals/eclinm/article/PIIS2589-5...
“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.
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.
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.
* https://blogs.sciencemag.org/pipeline/archives/2020/07/15/mo...
* https://blogs.sciencemag.org/pipeline/archives/2020/07/20/mo...
* https://blogs.sciencemag.org/pipeline/archives/2020/07/20/ne...
(these blogs link the actual preprint primary source as well)
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).