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Is it implausible to think that continued transmission and mutation at this rate will cause a catastrophic worsening of the pandemic to an extent several orders

Is it implausible to think that continued transmission and mutation at this rate will cause a catastrophic worsening of the pandemic to an extent several orders of magnitude above what it is now? Vaccination is effective in the current state of the pandemic, but what's to prevent the built-up immune response of humankind being wiped out if the virus adapts enough?

slumdev 5y ago
SARS-CoV-2 has four antigens. The existing vaccines stimulate the production of antibodies against only one of them, the spike protein. The existing vaccines are proving ineffective against Delta because it has mutated significantly enough that its spike protein does not cause a neutralizing immune response. They may even be causing ADE, as evidenced by the most recent data comparing Israel and Palestine.
- bushbaba 5y ago
  Palestine is ambiguous. I assume you mean Gaza or West Bank? To Palestinians the entire country of Israel is Palestine. Hence the chant from the river to the sea Palestine will be free.
  - etc-hosts 5y ago
    Obviously the OP is referring to West Bank and Gaza.
    - bushbaba 5y ago
      There are Palestinians living in east Jerusalem. There’s Palestinians who are citizens of Israel. His use of wording was ambiguous.
      - etc-hosts 5y ago
        you know what they mean, don't be dense.
- selimthegrim 5y ago
  Uh... citation? And as you know, neutralizing response is not the only type.
  - slumdev 5y ago
    A study demonstrating the mechanism for Delta ADE in vivo: https://pubmed.ncbi.nlm.nih.gov/34384810/ https://pubmed.ncbi.nlm.nih.gov/34384810/ Highly-vaccinated Israel's third-wave surge in both cases and deaths: https://www.worldometers.info/coronavirus/country/israel/ https://www.worldometers.info/coronavirus/country/israel/ Unvaccinated Palestine's lack of third wave deaths: https://www.worldometers.info/coronavirus/country/state-of-palestine/ https://www.worldometers.info/coronavirus/country/state-of-p...
    - Mordisquitos 5y ago
      > A study demonstrating the mechanism for Delta ADE in vivo: https://pubmed.ncbi.nlm.nih.gov/34384810/ https://pubmed.ncbi.nlm.nih.gov/34384810/ Not only is that article not a study but rather a letter to the editor, but also in their last paragraph they explicitly state that ADE in SARS-CoV-2 has never been demonstrated in vivo. Here is the relevant quote from the letter: >[...] Although this potential risk has been cleverly anticipated before the massive use of Covid-19 vaccines6, the ability of SARS-CoV-2 antibodies to mediate infection enhancement in vivo has never been formally demonstrated. [...]
      - deleted 5y ago
        [deleted]
    - walterbell 5y ago
      Thanks for the Israel-Palestine comparison.
    - jdkuepper 5y ago
      Here is a more in-depth counterpoint to that preprint: https://blogs.sciencemag.org/pipeline/archives/2021/08/16/a-new-antibody-dependent-enhancement-hypothesis https://blogs.sciencemag.org/pipeline/archives/2021/08/16/a-...
- YPCrumble 5y ago
  Do you have a source for the recent data on ADE? I searched and didn’t find anything suggesting this. The only thing I see are studies that more vaccinated people are dying in Israel, but that is to be expected because the older people are, the more likely they are to be vaccinated and they have less immune response to the vaccine. Source https://twitter.com/rzioni/status/1426178482569109504 https://twitter.com/rzioni/status/1426178482569109504
  - slumdev 5y ago
    See my reply to a sibling comment. The most damning evidence comes from the comparison between highly-vaccinated Israel, where there are many third-wave deaths, and mostly-unvaccinated Palestine, where there isn't a third-wave death spike at all. Having mostly-unvaccinated Palestine as a control group is showing us that we don't know what we thought we knew.
    - rdedev 5y ago
      The graphs you've mentioned in your sibling comment does not separate deaths based on vaccination. Here is another source that takes this into account. Vaccination does reduce chances of severe infections even in delta, though it's not as good as before: https://www.npr.org/sections/goatsandsoda/2021/08/20/1029628471/highly-vaccinated-israel-is-seeing-a-dramatic-surge-in-new-covid-cases-heres-why https://www.npr.org/sections/goatsandsoda/2021/08/20/1029628... > The good news is that among Israel's serious infections on Thursday of this week, according to Health Ministry data, there were nine times more serious cases among unvaccinated people over age 60 (178.7 per 100,000) than among fully vaccinated people of the same age category, and a little more than double the number of serious infections among unvaccinated people in the under-60 crowd (3.2 per 100,000) than among the vaccinated in that age bracket. Also do note that official numbers from Palestine could be undercounted because of the situation there
- OneLeggedCat 5y ago
  > existing vaccines stimulate the production of antibodies against only one of them Is this true for the J&J vax as well?
  - desine 5y ago
    Yes the J&J shot still works using only the spike protein. IIRC only Novavax uses traditional inoculation of using the weakened SARS-CoV-2 virus.
    - polynomial 5y ago
      weakened how?
      - nradov 5y ago
        Some of the current vaccines are produced by mixing batches of SARS-CoV-2 virions with beta-Propiolactone to make them inactive.
    - raphlinus 5y ago
      Novavax is a protein subunit vaccine, with the spike protein only. The Chinese CoronaVac and Indian Covaxin are traditional inactivated virus vaccines.
      - OneLeggedCat 5y ago
        ... Does that mean that CoronaVac and Covaxin might eventually prove better than current vaccines widely available in the US?
        raphlinus 5y ago
        That seems very unlikely. If a variant evolves that has significant evasion of the vaccines, then we should be able to retool the mRNA vaccines quickly. And T-cell response is more robust to antigenic drift than the antibody response, though not as well studied. See [1] for a very detailed investigation into antigenic drift and vaccine evasion. [1]: https://www.nature.com/articles/s41579-021-00573-0 https://www.nature.com/articles/s41579-021-00573-0
silicon2401 5y ago
People believe what's comfortable/convenient, not what's true. In very early 2020, when I was following the news of the virus development in Wuhan, China, I felt like a conspiracy theorist pointing out to friends and coworkers that a bad epidemic spreading in one of the most crowded parts of the world. They thought it was ridiculous to say that hospitals were getting overwhelmed, people were being quarantined etc. Don't even think about suggesting it'll spread outside of China, or that the virus may have come from the lab that just so happened to also be in the origin of the epidemic, a lab which specialized in highly infectious diseases. Not even 2 years later and where are we now? The entire world got sick and pretty much every country has done lockdowns/quarantines/shutdowns. Not to mention the lab theory of the virus origin still can't be ruled out. Even after the pandemic started, people still had no problem sticking their head in the sand. It's not a big deal; it's 2020, we have technology and medicine and we'll just make a vaccine and get back to normal. Well now it's almost 2022 and somehow things just keep getting worse. We can reasonably say the Black Death killed 30% of Europe's population. We can't reasonably say covid won't do the same. All optimistic projections so far have been proven wrong, so all we can say for sure is that humans are terrible at predicting the future.
- desine 5y ago
  >We can reasonably say the Black Death killed 30% of Europe's population. We can't reasonably say covid won't do the same. All optimistic projections so far have been proven wrong, so all we can say for sure is that humans are terrible at predicting the future. I think Black Death had quite a bit higher mortality than any version of covid we will see
- nradov 5y ago
  That's just fear mongering nonsense, like claiming that we can't reasonably say that aliens won't invade the Earth tomorrow. I mean I can't prove it's impossible but come on. There's no scientific evidence that a coronavirus can be both highly contagious and have a 30% fatality rate. CDC data clearly shows that the fatality rate in the US has been 0.6%, largely because we have a lot of vulnerable elderly people with serious co-morbid conditions. The fatality rate in countries with younger, healthier populations is far lower. And for vaccinated people of all ages the death rate is close to 0.
cjfd 5y ago
Both the worst-case and the best-case scenario are on the table. Only time will tell what happens. As you seem to be focusing on the worst-case scenario I will talk about the best-case scenario. The best-case scenario is that the human immune system is getting used to corona with even vaccinated people spreading the delta variant with little chance of getting very ill. This will turn covid-19 into something like the common cold or possibly the flu. Who knows what will actually happen? Both my best-case scenario and your worst-case scenario can happen. I think, though, that one should not only focus on the adaptability of the virus. The immune system also has been doing defense against various pathogens for many millions of years.
- achenatx 5y ago
  The likely scenario is that it turns into cold/flu. Everyone either gets the vaccine or the virus and we are all mostly immune. It mutates a little and once it mutates just enough to spread substantially everyone who gets it gets immune. Only a fraction of the population will get any particular mutation. I remember having the debate that herd immunity has never happened without a vaccine. Which is just BS. Every disease throughout history has eventually reached equilibrium with humans which is essentially herd immunity. Most mutations are point mutations. Once enough point mutations accumulate that give the virus superior ability to spread, it will. It is unlikely that any point mutation will suddenly make the virus orders of magnitude more deadly.
  - empthought 5y ago
    You don't understand what "herd immunity" means. Herd immunity means eliminating a disease within a community ("herd"). It does not mean endemic case incidence with socially tolerable outcomes, or whatever loosey-goosey idea you mean by "equilibrium." Herd immunity means the contagion is eliminated. It has never happened worldwide without a vaccine, and I'm unaware of any virus where it has been sustained within a community without a vaccine. How could it? The only paths to immunity are vaccine or exposure, and exposure depends on the virus actually circulating.
    - 5y ago
Mordisquitos 5y ago
No, it is not implausible in the sense that "it could never happen". However, neither was it implausible for this to have happened with the myriad of other viruses which have jumped into our species across our natural history—and yet here we are. Remember there is no motivation behind the virus to adapt, nor such thing as "wiping out" the immune response. At most, there are random mutations which, if they are more successful than the previous ones, will become more widespread than their alternatives. Are mutations that are less sensitive to current populations' immune responses more likely to succeed? Yes, of course! But there is a practical limitation to how much a virus can accumulate mutations which evade immunity to previous variants: it must not break its ability to infect (human) cells. Eventually an equilibrium is reached, as it has thousands of times previously.
naasking 5y ago
Not implausible at all. Mutation rate is proportional to the number of infected. Third world countries have barely even started vaccinating. There's a lot of room for nightmare scenarios. Which is why I think it was a bone-headed move to not suspend patent protection on the vaccines. Thanks Bill Gates!
- rdedev 5y ago
  This. The Astra zenca vaccine, originally designed by the Oxford University, was supposed to be open licenced. But the gates foundation convinced them otherwise. The top priority should have been to get as many vaccine factories open as soon as possible but even functioning factories had trouble starting talks with bigshots like pfizer https://www.seattletimes.com/seattle-news/health/have-gates-foundation-efforts-to-vaccinate-the-world-against-covid-19-helped-or-hindered/ https://www.seattletimes.com/seattle-news/health/have-gates-... https://apnews.com/article/drug-companies-called-share-vaccine-info-22d92afbc3ea9ed519be007f8887bcf6 https://apnews.com/article/drug-companies-called-share-vacci... https://newrepublic.com/article/162000/bill-gates-impeded-global-access-covid-vaccines https://newrepublic.com/article/162000/bill-gates-impeded-gl...
- rudedogg 5y ago
  The Bill Gates mention set off my conspiracy nut alarm bells, but after reading this entire article[0] the criticism seems fair. [0] https://www.devex.com/news/gates-foundation-reverses-course-on-covid-19-vaccine-patents-99810 https://www.devex.com/news/gates-foundation-reverses-course-...
dehrmann 5y ago
It's gotten ~2x more contagious and slightly more virulent in the past 18 months. If training ML models taught me anything, in the near term, it will continue in the same direction, but the gains will be much smaller.

slumdev 5y ago

SARS-CoV-2 has four antigens. The existing vaccines stimulate the production of antibodies against only one of them, the spike protein. The existing vaccines are proving ineffective against Delta because it has mutated significantly enough that its spike protein does not cause a neutralizing immune response. They may even be causing ADE, as evidenced by the most recent data comparing Israel and Palestine.

bushbaba 5y ago
Palestine is ambiguous. I assume you mean Gaza or West Bank? To Palestinians the entire country of Israel is Palestine. Hence the chant from the river to the sea Palestine will be free.
- etc-hosts 5y ago
  Obviously the OP is referring to West Bank and Gaza.
  - bushbaba 5y ago
    There are Palestinians living in east Jerusalem. There’s Palestinians who are citizens of Israel. His use of wording was ambiguous.
    - etc-hosts 5y ago
      you know what they mean, don't be dense.
selimthegrim 5y ago
Uh... citation? And as you know, neutralizing response is not the only type.
- slumdev 5y ago
  A study demonstrating the mechanism for Delta ADE in vivo: https://pubmed.ncbi.nlm.nih.gov/34384810/ https://pubmed.ncbi.nlm.nih.gov/34384810/ Highly-vaccinated Israel's third-wave surge in both cases and deaths: https://www.worldometers.info/coronavirus/country/israel/ https://www.worldometers.info/coronavirus/country/israel/ Unvaccinated Palestine's lack of third wave deaths: https://www.worldometers.info/coronavirus/country/state-of-palestine/ https://www.worldometers.info/coronavirus/country/state-of-p...
  - Mordisquitos 5y ago
    > A study demonstrating the mechanism for Delta ADE in vivo: https://pubmed.ncbi.nlm.nih.gov/34384810/ https://pubmed.ncbi.nlm.nih.gov/34384810/ Not only is that article not a study but rather a letter to the editor, but also in their last paragraph they explicitly state that ADE in SARS-CoV-2 has never been demonstrated in vivo. Here is the relevant quote from the letter: >[...] Although this potential risk has been cleverly anticipated before the massive use of Covid-19 vaccines6, the ability of SARS-CoV-2 antibodies to mediate infection enhancement in vivo has never been formally demonstrated. [...]
    - deleted 5y ago
      [deleted]
  - walterbell 5y ago
    Thanks for the Israel-Palestine comparison.
  - jdkuepper 5y ago
    Here is a more in-depth counterpoint to that preprint: https://blogs.sciencemag.org/pipeline/archives/2021/08/16/a-new-antibody-dependent-enhancement-hypothesis https://blogs.sciencemag.org/pipeline/archives/2021/08/16/a-...
YPCrumble 5y ago
Do you have a source for the recent data on ADE? I searched and didn’t find anything suggesting this. The only thing I see are studies that more vaccinated people are dying in Israel, but that is to be expected because the older people are, the more likely they are to be vaccinated and they have less immune response to the vaccine. Source https://twitter.com/rzioni/status/1426178482569109504 https://twitter.com/rzioni/status/1426178482569109504
- slumdev 5y ago
  See my reply to a sibling comment. The most damning evidence comes from the comparison between highly-vaccinated Israel, where there are many third-wave deaths, and mostly-unvaccinated Palestine, where there isn't a third-wave death spike at all. Having mostly-unvaccinated Palestine as a control group is showing us that we don't know what we thought we knew.
  - rdedev 5y ago
    The graphs you've mentioned in your sibling comment does not separate deaths based on vaccination. Here is another source that takes this into account. Vaccination does reduce chances of severe infections even in delta, though it's not as good as before: https://www.npr.org/sections/goatsandsoda/2021/08/20/1029628471/highly-vaccinated-israel-is-seeing-a-dramatic-surge-in-new-covid-cases-heres-why https://www.npr.org/sections/goatsandsoda/2021/08/20/1029628... > The good news is that among Israel's serious infections on Thursday of this week, according to Health Ministry data, there were nine times more serious cases among unvaccinated people over age 60 (178.7 per 100,000) than among fully vaccinated people of the same age category, and a little more than double the number of serious infections among unvaccinated people in the under-60 crowd (3.2 per 100,000) than among the vaccinated in that age bracket. Also do note that official numbers from Palestine could be undercounted because of the situation there
OneLeggedCat 5y ago
> existing vaccines stimulate the production of antibodies against only one of them Is this true for the J&J vax as well?
- desine 5y ago
  Yes the J&J shot still works using only the spike protein. IIRC only Novavax uses traditional inoculation of using the weakened SARS-CoV-2 virus.
  - polynomial 5y ago
    weakened how?
    - nradov 5y ago
      Some of the current vaccines are produced by mixing batches of SARS-CoV-2 virions with beta-Propiolactone to make them inactive.
  - raphlinus 5y ago
    Novavax is a protein subunit vaccine, with the spike protein only. The Chinese CoronaVac and Indian Covaxin are traditional inactivated virus vaccines.
    - OneLeggedCat 5y ago
      ... Does that mean that CoronaVac and Covaxin might eventually prove better than current vaccines widely available in the US?
      - raphlinus 5y ago
        That seems very unlikely. If a variant evolves that has significant evasion of the vaccines, then we should be able to retool the mRNA vaccines quickly. And T-cell response is more robust to antigenic drift than the antibody response, though not as well studied. See [1] for a very detailed investigation into antigenic drift and vaccine evasion. [1]: https://www.nature.com/articles/s41579-021-00573-0 https://www.nature.com/articles/s41579-021-00573-0

silicon2401 5y ago

People believe what's comfortable/convenient, not what's true. In very early 2020, when I was following the news of the virus development in Wuhan, China, I felt like a conspiracy theorist pointing out to friends and coworkers that a bad epidemic spreading in one of the most crowded parts of the world. They thought it was ridiculous to say that hospitals were getting overwhelmed, people were being quarantined etc. Don't even think about suggesting it'll spread outside of China, or that the virus may have come from the lab that just so happened to also be in the origin of the epidemic, a lab which specialized in highly infectious diseases. Not even 2 years later and where are we now? The entire world got sick and pretty much every country has done lockdowns/quarantines/shutdowns. Not to mention the lab theory of the virus origin still can't be ruled out. Even after the pandemic started, people still had no problem sticking their head in the sand. It's not a big deal; it's 2020, we have technology and medicine and we'll just make a vaccine and get back to normal. Well now it's almost 2022 and somehow things just keep getting worse. We can reasonably say the Black Death killed 30% of Europe's population. We can't reasonably say covid won't do the same. All optimistic projections so far have been proven wrong, so all we can say for sure is that humans are terrible at predicting the future.

desine 5y ago
>We can reasonably say the Black Death killed 30% of Europe's population. We can't reasonably say covid won't do the same. All optimistic projections so far have been proven wrong, so all we can say for sure is that humans are terrible at predicting the future. I think Black Death had quite a bit higher mortality than any version of covid we will see
nradov 5y ago
That's just fear mongering nonsense, like claiming that we can't reasonably say that aliens won't invade the Earth tomorrow. I mean I can't prove it's impossible but come on. There's no scientific evidence that a coronavirus can be both highly contagious and have a 30% fatality rate. CDC data clearly shows that the fatality rate in the US has been 0.6%, largely because we have a lot of vulnerable elderly people with serious co-morbid conditions. The fatality rate in countries with younger, healthier populations is far lower. And for vaccinated people of all ages the death rate is close to 0.

cjfd 5y ago

Both the worst-case and the best-case scenario are on the table. Only time will tell what happens. As you seem to be focusing on the worst-case scenario I will talk about the best-case scenario. The best-case scenario is that the human immune system is getting used to corona with even vaccinated people spreading the delta variant with little chance of getting very ill. This will turn covid-19 into something like the common cold or possibly the flu. Who knows what will actually happen? Both my best-case scenario and your worst-case scenario can happen. I think, though, that one should not only focus on the adaptability of the virus. The immune system also has been doing defense against various pathogens for many millions of years.

achenatx 5y ago
The likely scenario is that it turns into cold/flu. Everyone either gets the vaccine or the virus and we are all mostly immune. It mutates a little and once it mutates just enough to spread substantially everyone who gets it gets immune. Only a fraction of the population will get any particular mutation. I remember having the debate that herd immunity has never happened without a vaccine. Which is just BS. Every disease throughout history has eventually reached equilibrium with humans which is essentially herd immunity. Most mutations are point mutations. Once enough point mutations accumulate that give the virus superior ability to spread, it will. It is unlikely that any point mutation will suddenly make the virus orders of magnitude more deadly.
- empthought 5y ago
  You don't understand what "herd immunity" means. Herd immunity means eliminating a disease within a community ("herd"). It does not mean endemic case incidence with socially tolerable outcomes, or whatever loosey-goosey idea you mean by "equilibrium." Herd immunity means the contagion is eliminated. It has never happened worldwide without a vaccine, and I'm unaware of any virus where it has been sustained within a community without a vaccine. How could it? The only paths to immunity are vaccine or exposure, and exposure depends on the virus actually circulating.
  - 5y ago

Mordisquitos 5y ago

No, it is not implausible in the sense that "it could never happen". However, neither was it implausible for this to have happened with the myriad of other viruses which have jumped into our species across our natural history—and yet here we are. Remember there is no motivation behind the virus to adapt, nor such thing as "wiping out" the immune response. At most, there are random mutations which, if they are more successful than the previous ones, will become more widespread than their alternatives. Are mutations that are less sensitive to current populations' immune responses more likely to succeed? Yes, of course! But there is a practical limitation to how much a virus can accumulate mutations which evade immunity to previous variants: it must not break its ability to infect (human) cells. Eventually an equilibrium is reached, as it has thousands of times previously.

naasking 5y ago

Not implausible at all. Mutation rate is proportional to the number of infected. Third world countries have barely even started vaccinating. There's a lot of room for nightmare scenarios. Which is why I think it was a bone-headed move to not suspend patent protection on the vaccines. Thanks Bill Gates!

rdedev 5y ago
This. The Astra zenca vaccine, originally designed by the Oxford University, was supposed to be open licenced. But the gates foundation convinced them otherwise. The top priority should have been to get as many vaccine factories open as soon as possible but even functioning factories had trouble starting talks with bigshots like pfizer https://www.seattletimes.com/seattle-news/health/have-gates-foundation-efforts-to-vaccinate-the-world-against-covid-19-helped-or-hindered/ https://www.seattletimes.com/seattle-news/health/have-gates-... https://apnews.com/article/drug-companies-called-share-vaccine-info-22d92afbc3ea9ed519be007f8887bcf6 https://apnews.com/article/drug-companies-called-share-vacci... https://newrepublic.com/article/162000/bill-gates-impeded-global-access-covid-vaccines https://newrepublic.com/article/162000/bill-gates-impeded-gl...
rudedogg 5y ago
The Bill Gates mention set off my conspiracy nut alarm bells, but after reading this entire article[0] the criticism seems fair. [0] https://www.devex.com/news/gates-foundation-reverses-course-on-covid-19-vaccine-patents-99810 https://www.devex.com/news/gates-foundation-reverses-course-...

dehrmann 5y ago

It's gotten ~2x more contagious and slightly more virulent in the past 18 months. If training ML models taught me anything, in the near term, it will continue in the same direction, but the gains will be much smaller.