15 ms·

40-60% of the unexposed produce Covid-19 antibodies due to earlier cold exposure [pdf]

95 points by cangencer 6y ago

hbarka 6y ago
Does this mean they have immunity? Is it a false positive?
- metalliqaz 6y ago
  Not immunity but a much better immune response, assuming they are healthy.
aristophenes 6y ago
Does this mean that it was much more contagious than thought, if it spreads so fast while so many already have some immunity? Also, if 1/4 of New York City has already had covid-19, then maybe there is only ~1/4 left who wouldn't have immunity. Which would imply that if all restrictions were lifted (in NYC) the "curve" of new infections would be much lower than the first one.
- fxtentacle 6y ago
  I believe this research only shows that their immune system has some sort of defense against covid, but not that they'll be immune.
  - joaomacp 6y ago
    Does this explain asymptomatic cases? Maybe people don't develop symptoms because they have cold-related antibodies that don't let COVID develop. Can these people still shed and transmit SARS-CoV-2?
    - fxtentacle 6y ago
      It sadly appears that many people who recover from covid have temporary or permanent (not known yet) lung damage anyway. So those asymptomatic might simply be people whose natural lung operation is strong enough that they can compensate for the covid damage.
  - jfnixon 6y ago
    The response was primarily by Th cells, not the TC cells, so yes, this isn't immunity, but it would speed to body's adaptive immune system response. OTOH, the killer feature of Covid-19 seems to be triggering an out-of-control adaptive immune response. That's probably why kids aren't dying, as their adaptive immune response is still developing.
- gvb 6y ago
  It means that people that have the at least one common antibody from exposure to the common cold as those that have had COVID-19. The implication (in the best of all possible worlds) is that the antibodies that fight common cold also fight COVID-19. Or it could be a simple correlation and not significant.
- elmerfud 6y ago
  No it doesn't mean that at all. What this is telling you and what media has been avoiding saying is that coronavirus is a family of viruses that make up the common cold. It's not the only virus that's lumped in as the common cold but it is one kind. Coronavirus isn't new, covid19 is just a previously unknown variation. What is paper is saying is that previous exposure to coronavirus (the common cold) grants some level of immunity to covid19.
  - CydeWeys 6y ago
    > coronavirus is a family of viruses that make up the common cold Wrong. There are 200+ strains of various viruses that are all lumped together as the "common cold" only 4 of which are coronaviruses. The vast majority of common colds are not coronaviruses.
    - elmerfud 6y ago
      I guess reading is hard when it's longer than a Twitter post because my very next sentence was. > It's not the only virus that's lumped in as the common cold but it is one kind. Perhaps not having knee jerk reactions and careful examination of the information is what's needed.
  - antonvs 6y ago
    > What is paper is saying is that previous exposure to coronavirus (the common cold) grants some level of immunity to covid19. It's not saying that. The presence of these antibodies does not necessarily mean any level of immunity against SARS-CoV-2, which is a different virus than the one that triggered these antibodies. The degree to which these antibodies contribute towards immunity against the new virus is unknown, and wasn't evaluated by this study.
- alkonaut 6y ago
  The effective R is R(0) multiplied by (among other things) the susceptible population. If those with existing protection are still susceptible and still become infectious when infected, then this does't change the evolution. It's likely that those who are infected but have some immunity develops a less severe illness, which is possibly less infectious. But there is something that works in the opposite direction: if those with some protection become asymptomatic or mildly symptomatic but are still spreaders, then their lack of symptoms might mean they move around more and have more contacts, outweighing their smaller level of infectiousness. We can't know. If those with existing protection can't become spreaders, then it should indeed mean that the R0 is much higher than expected (It was estimated from doubling assuming 100% were initially susceptible, so if only 50% were initially susceptible then the estimate would be off by a factor 2). But I don't think that this is what the paper is saying. It's saying that some have partial immunity responses that deal with the infection. They still get immunity after their infection, not before.
walterbell 6y ago
> 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 This is saying that 40-60% of existing immune responses (learned over many years of previous coronaviruses) are also protective against the SARS-Cov-2 virus which causes Covid-19 disease. There is a time-based arms race between virus replication & immune defense. If these subjects are otherwise healthy, their immune system should have a good chance of clearing the Covid-19 virus successfully, because it has a "running start" against the new virus. After recovery, their adaptive immune system should have developed an additional immune response that is customized to defend against Covid-19.
- dkdk8283 6y ago
  > If they are otherwise healthy, their immune system should have a good chance of clearing the Covid-19 virus Yet we decimated our economy out of an absolute panic and still continue to push for lockdown even when numbers show it’s time to start things again.
  - WrtCdEvrydy 6y ago
    > decimated our economy out of an absolute panic and still continue to push for lockdown 80,000 Americans died, and thousands more will die before this is over.
    - CydeWeys 6y ago
      And that's with the lockdowns. The figures could easily be an order of magnitude or more worse be now without them. We successfully managed to not exceed the capacity of our healthcare system, for the most part.
      - whatshisface 6y ago
        That's not past tense yet...
      - 6y ago
user_50123890 6y ago
Surely almost all elderly people should have antibodies then due to decades of exposure to the other coronaviruses?
- walterbell 6y ago
  Yes, but they could have other risks due to existing medical conditions. It's an arms race between the speed of replication of the invading virus, and the immune system's ability to respond. Existing conditions add many complications. If they interact regularly with family and were long exposed to commonly circulating viruses (e.g. from kids), they would have a resilient/diverse immune system. This assumes a healthy diet with no deficiencies (Vitamin C, D, Zinc). Another complicating factor is the content of flu vaccines.
  - Fjolsvith 6y ago
    Are you saying that flu vaccines could make us more susceptible to COVID-19 and other coronavirus infections?
    - walterbell 6y ago
      The term "flu vaccine" is as meaningful as "glass of liquid". Depends what's in the glass. The content of vaccines vary across geographical regions and their very purpose is to interact with the immune system. The precise contents of previous vaccines should be tracked and analyzed in studies of elderly immune system responses to SARS-Cov-2.
- mynegation 6y ago
  Disclaimer: not an immunologist, no formal post secondary biological education, my thoughts on this are likely worthless. I had the same question when it all started: how exposure to other coronaviruses affects the response to SARS-Cov-2, and what does it mean for people with different history of exposures. One hypothesis was that older people have a higher probability of dying because their immune system does not produce antibodies fast enough to keep up with the virus. The other one was the complete opposite: that due to the long history of exposures to other coronaviruses they have too much of a response and cytokine storm as a result but that does not seem to be the case.
guscost 6y ago
And these antibodies are excluded by any test specific to COVID-19 (since this situation would be considered a false-positive).
lysp 6y ago
Twitter chain: https://twitter.com/profshanecrotty/status/1261052353773363200 https://twitter.com/profshanecrotty/status/12610523537733632...
s9w 6y ago
This seems like a euphemism for "the tests are bad"
mberning 6y ago
How do they know for sure people have not been exposed? I don’t see how you could prove definitively that a person wasn’t. And with many cases being asymptomatic they could have had it long ago and not known.
- mbrubeck 6y ago
  The unexposed samples were from blood draws taken from 2015 to 2018.
  - mberning 6y ago
    Right. Blood from 3-4 years ago has antibodies. One interpretation could be that those people were never exposed but somehow have antibodies which needs investigation. Another interpretation could be that covid-19 is a particularly bad seasonal strain of a disease that has been around for a long time. We probably will never know. People are still studying SARS and MERS.
- j4kp07 6y ago
  "All of the donors were recruited between 2015-2018, excluding any possibility of exposure to SARS-CoV-2."
ridewinter 6y ago
Couldn't this explain why children are at less risk? They are constantly catching various common colds.
- ramraj07 6y ago
  There seem to be other reasons too, apparently the activity of Antigen Presenting Cells (another cog required in the production of the immune response) deteriorates with age, as pointed in this papers introduction section.
deleted 6y ago
[deleted]
sjg007 6y ago
This seems weird to me though. New Yorkers should have wide exposure to the common cold due to density, as would people in Wuhan.. why was this sars-cov2 so lethal then?
- JackFr 6y ago
  More than 1/3 the fatalities in NY were in nursing homes. Nursing homes in NY were required to readmit recovering patients coming back from the hospital. Thanks Gov. Cuomo!
  - gpapilion 6y ago
    This is the common theme, in California the number was 50% at one point. Most explanations I’ve seen is the fatality rate increase with age from a small factional percentage to 10% in those in their 70s and 80s. That combined with the proximity of people at a nursing home make it especially deadly.
    - mardifoufs 6y ago
      Nursing homes account for 70% of fatalities here in Quebec! And retirement homes 20%. It's very telling that we shut everything up here, with very intense measures compared to our neighbors, but we just utterly ignored nursing houses. We were giving fines to 13yo kids playing soccer in parks when nursing home patients were still going in and out freely and their caregivers were encouraged not to wear PPE (not that it was available anyways, it was mostly diverted to hospitals...). New york did a similar mistake by forcing nursing homes to accept recovering COVID patients, with disastrous results too.
- sulam 6y ago
  Just having these antibodies does not mean you will not still catch Covid.
caiobegotti 6y ago
If I understood it right they checked that against two groups of 20 people (40 in total only). The study itself seems super interesting and important but such ridiculously small sample size to me, a layman following COVID-19-related research. Is 40 acceptable in this case? Since they are on Cell.com I suppose it is. Bad sample size in COVID-19 research has been discussed recently already and it is a known problem. Another thing is that the sample size was a hidden lead in page 3 and a figure shown only in page 11 of the paper. I wish scientific papers had something of a "nutrition facts" label with basic info like that in their first page.
- ramraj07 6y ago
  This is not a clinical trial though, merely a mechanistic study. The types of assays they have done typically take years to get right with just a handful of samples so it's actually quite impressive. Importantly this is a T cell study not exactly an antibody assay study (t cell responses are a prerequisite for antibody responses).
- Someone 6y ago
  Yes, the paper could’ve been written better. The normal presentation order is abstract-introduction-methods-results-discussion. Here, they mix the methods and the results/hide the methods inside the results. I don’t understand the paper well enough to even try to check the statistics (if there is any; I didn’t see clear claims, so this may just be a ‘here is what we observed’ paper), but you can’t disqualify a paper on sample size alone. 20 can be large enough if the effect is large enough. For example, if you do heads/tails 20 times with a fair coin, the probability to get more than 15 heads is less than 1%, so if you get, say, 17, the hypothesis that the coin is fair can be rejected.
deleted 6y ago
[deleted]
scotty79 6y ago
Does this mean that specificity of commercially available Igg covid tests is actually lower than advertised?

95 points by cangencer 6y ago

hbarka 6y ago

Does this mean they have immunity? Is it a false positive?

metalliqaz 6y ago
Not immunity but a much better immune response, assuming they are healthy.

aristophenes 6y ago

Does this mean that it was much more contagious than thought, if it spreads so fast while so many already have some immunity? Also, if 1/4 of New York City has already had covid-19, then maybe there is only ~1/4 left who wouldn't have immunity. Which would imply that if all restrictions were lifted (in NYC) the "curve" of new infections would be much lower than the first one.

fxtentacle 6y ago
I believe this research only shows that their immune system has some sort of defense against covid, but not that they'll be immune.
- joaomacp 6y ago
  Does this explain asymptomatic cases? Maybe people don't develop symptoms because they have cold-related antibodies that don't let COVID develop. Can these people still shed and transmit SARS-CoV-2?
  - fxtentacle 6y ago
    It sadly appears that many people who recover from covid have temporary or permanent (not known yet) lung damage anyway. So those asymptomatic might simply be people whose natural lung operation is strong enough that they can compensate for the covid damage.
- jfnixon 6y ago
  The response was primarily by Th cells, not the TC cells, so yes, this isn't immunity, but it would speed to body's adaptive immune system response. OTOH, the killer feature of Covid-19 seems to be triggering an out-of-control adaptive immune response. That's probably why kids aren't dying, as their adaptive immune response is still developing.
gvb 6y ago
It means that people that have the at least one common antibody from exposure to the common cold as those that have had COVID-19. The implication (in the best of all possible worlds) is that the antibodies that fight common cold also fight COVID-19. Or it could be a simple correlation and not significant.
elmerfud 6y ago
No it doesn't mean that at all. What this is telling you and what media has been avoiding saying is that coronavirus is a family of viruses that make up the common cold. It's not the only virus that's lumped in as the common cold but it is one kind. Coronavirus isn't new, covid19 is just a previously unknown variation. What is paper is saying is that previous exposure to coronavirus (the common cold) grants some level of immunity to covid19.
- CydeWeys 6y ago
  > coronavirus is a family of viruses that make up the common cold Wrong. There are 200+ strains of various viruses that are all lumped together as the "common cold" only 4 of which are coronaviruses. The vast majority of common colds are not coronaviruses.
  - elmerfud 6y ago
    I guess reading is hard when it's longer than a Twitter post because my very next sentence was. > It's not the only virus that's lumped in as the common cold but it is one kind. Perhaps not having knee jerk reactions and careful examination of the information is what's needed.
- antonvs 6y ago
  > What is paper is saying is that previous exposure to coronavirus (the common cold) grants some level of immunity to covid19. It's not saying that. The presence of these antibodies does not necessarily mean any level of immunity against SARS-CoV-2, which is a different virus than the one that triggered these antibodies. The degree to which these antibodies contribute towards immunity against the new virus is unknown, and wasn't evaluated by this study.
alkonaut 6y ago
The effective R is R(0) multiplied by (among other things) the susceptible population. If those with existing protection are still susceptible and still become infectious when infected, then this does't change the evolution. It's likely that those who are infected but have some immunity develops a less severe illness, which is possibly less infectious. But there is something that works in the opposite direction: if those with some protection become asymptomatic or mildly symptomatic but are still spreaders, then their lack of symptoms might mean they move around more and have more contacts, outweighing their smaller level of infectiousness. We can't know. If those with existing protection can't become spreaders, then it should indeed mean that the R0 is much higher than expected (It was estimated from doubling assuming 100% were initially susceptible, so if only 50% were initially susceptible then the estimate would be off by a factor 2). But I don't think that this is what the paper is saying. It's saying that some have partial immunity responses that deal with the infection. They still get immunity after their infection, not before.

walterbell 6y ago

> 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 This is saying that 40-60% of existing immune responses (learned over many years of previous coronaviruses) are also protective against the SARS-Cov-2 virus which causes Covid-19 disease. There is a time-based arms race between virus replication & immune defense. If these subjects are otherwise healthy, their immune system should have a good chance of clearing the Covid-19 virus successfully, because it has a "running start" against the new virus. After recovery, their adaptive immune system should have developed an additional immune response that is customized to defend against Covid-19.

dkdk8283 6y ago
> If they are otherwise healthy, their immune system should have a good chance of clearing the Covid-19 virus Yet we decimated our economy out of an absolute panic and still continue to push for lockdown even when numbers show it’s time to start things again.
- WrtCdEvrydy 6y ago
  > decimated our economy out of an absolute panic and still continue to push for lockdown 80,000 Americans died, and thousands more will die before this is over.
  - CydeWeys 6y ago
    And that's with the lockdowns. The figures could easily be an order of magnitude or more worse be now without them. We successfully managed to not exceed the capacity of our healthcare system, for the most part.
    - whatshisface 6y ago
      That's not past tense yet...
    - 6y ago

user_50123890 6y ago

Surely almost all elderly people should have antibodies then due to decades of exposure to the other coronaviruses?

walterbell 6y ago
Yes, but they could have other risks due to existing medical conditions. It's an arms race between the speed of replication of the invading virus, and the immune system's ability to respond. Existing conditions add many complications. If they interact regularly with family and were long exposed to commonly circulating viruses (e.g. from kids), they would have a resilient/diverse immune system. This assumes a healthy diet with no deficiencies (Vitamin C, D, Zinc). Another complicating factor is the content of flu vaccines.
- Fjolsvith 6y ago
  Are you saying that flu vaccines could make us more susceptible to COVID-19 and other coronavirus infections?
  - walterbell 6y ago
    The term "flu vaccine" is as meaningful as "glass of liquid". Depends what's in the glass. The content of vaccines vary across geographical regions and their very purpose is to interact with the immune system. The precise contents of previous vaccines should be tracked and analyzed in studies of elderly immune system responses to SARS-Cov-2.
mynegation 6y ago
Disclaimer: not an immunologist, no formal post secondary biological education, my thoughts on this are likely worthless. I had the same question when it all started: how exposure to other coronaviruses affects the response to SARS-Cov-2, and what does it mean for people with different history of exposures. One hypothesis was that older people have a higher probability of dying because their immune system does not produce antibodies fast enough to keep up with the virus. The other one was the complete opposite: that due to the long history of exposures to other coronaviruses they have too much of a response and cytokine storm as a result but that does not seem to be the case.

guscost 6y ago

And these antibodies are excluded by any test specific to COVID-19 (since this situation would be considered a false-positive).

lysp 6y ago

Twitter chain: https://twitter.com/profshanecrotty/status/1261052353773363200 https://twitter.com/profshanecrotty/status/12610523537733632...

s9w 6y ago

This seems like a euphemism for "the tests are bad"

mberning 6y ago

How do they know for sure people have not been exposed? I don’t see how you could prove definitively that a person wasn’t. And with many cases being asymptomatic they could have had it long ago and not known.

mbrubeck 6y ago
The unexposed samples were from blood draws taken from 2015 to 2018.
- mberning 6y ago
  Right. Blood from 3-4 years ago has antibodies. One interpretation could be that those people were never exposed but somehow have antibodies which needs investigation. Another interpretation could be that covid-19 is a particularly bad seasonal strain of a disease that has been around for a long time. We probably will never know. People are still studying SARS and MERS.
j4kp07 6y ago
"All of the donors were recruited between 2015-2018, excluding any possibility of exposure to SARS-CoV-2."

ridewinter 6y ago

Couldn't this explain why children are at less risk? They are constantly catching various common colds.

ramraj07 6y ago
There seem to be other reasons too, apparently the activity of Antigen Presenting Cells (another cog required in the production of the immune response) deteriorates with age, as pointed in this papers introduction section.

deleted 6y ago

[deleted]

sjg007 6y ago

This seems weird to me though. New Yorkers should have wide exposure to the common cold due to density, as would people in Wuhan.. why was this sars-cov2 so lethal then?

JackFr 6y ago
More than 1/3 the fatalities in NY were in nursing homes. Nursing homes in NY were required to readmit recovering patients coming back from the hospital. Thanks Gov. Cuomo!
- gpapilion 6y ago
  This is the common theme, in California the number was 50% at one point. Most explanations I’ve seen is the fatality rate increase with age from a small factional percentage to 10% in those in their 70s and 80s. That combined with the proximity of people at a nursing home make it especially deadly.
  - mardifoufs 6y ago
    Nursing homes account for 70% of fatalities here in Quebec! And retirement homes 20%. It's very telling that we shut everything up here, with very intense measures compared to our neighbors, but we just utterly ignored nursing houses. We were giving fines to 13yo kids playing soccer in parks when nursing home patients were still going in and out freely and their caregivers were encouraged not to wear PPE (not that it was available anyways, it was mostly diverted to hospitals...). New york did a similar mistake by forcing nursing homes to accept recovering COVID patients, with disastrous results too.
sulam 6y ago
Just having these antibodies does not mean you will not still catch Covid.

caiobegotti 6y ago

If I understood it right they checked that against two groups of 20 people (40 in total only). The study itself seems super interesting and important but such ridiculously small sample size to me, a layman following COVID-19-related research. Is 40 acceptable in this case? Since they are on Cell.com I suppose it is. Bad sample size in COVID-19 research has been discussed recently already and it is a known problem. Another thing is that the sample size was a hidden lead in page 3 and a figure shown only in page 11 of the paper. I wish scientific papers had something of a "nutrition facts" label with basic info like that in their first page.

ramraj07 6y ago
This is not a clinical trial though, merely a mechanistic study. The types of assays they have done typically take years to get right with just a handful of samples so it's actually quite impressive. Importantly this is a T cell study not exactly an antibody assay study (t cell responses are a prerequisite for antibody responses).
Someone 6y ago
Yes, the paper could’ve been written better. The normal presentation order is abstract-introduction-methods-results-discussion. Here, they mix the methods and the results/hide the methods inside the results. I don’t understand the paper well enough to even try to check the statistics (if there is any; I didn’t see clear claims, so this may just be a ‘here is what we observed’ paper), but you can’t disqualify a paper on sample size alone. 20 can be large enough if the effect is large enough. For example, if you do heads/tails 20 times with a fair coin, the probability to get more than 15 heads is less than 1%, so if you get, say, 17, the hypothesis that the coin is fair can be rejected.

deleted 6y ago

[deleted]

scotty79 6y ago

Does this mean that specificity of commercially available Igg covid tests is actually lower than advertised?