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It is not yet clear whether infection with Omicron causes more severe disease compared to infections with other variants, including Delta. I thought this was w

It is not yet clear whether infection with Omicron causes more severe disease compared to infections with other variants, including Delta. I thought this was weirdly worded. It's also not clear whether Omicron disease is less severe, either, right? A long time ago, long before the pandemic politicized messaging so much, a researcher posted a comment here on HN where they said that virus deadliness and contagiousness were in tension.

azangru 5y ago
> a researcher posted a comment here on HN where they said that virus deadliness and contagiousness were in tension. I've heard this statement a lot, and have been rather puzzled by why this must be the case. It's certainly true over a long period of time (a deadly pathogen that will kill off its hosts too quickly will also perish); and it's also certainly true that if a pathogen is very contagious but not deadly it can replace a deadly but less contagious variant; but I don't believe there's any molecular mechanism that locks these two properties relative to one another and dictates that if a new variant is more contagious it is likely to be less deadly and vice versa.
- christophilus 5y ago
  There is no such mechanism, from what I’ve read (not an expert). Most diseases demonstrate the tension for the reason you give: too deadly too fast reduces transmission rate. But hypothetically, you could conceive of a disease with a high R value that is asymptomatic for the first month or two, and deadly in month three.
  - mschuster91 5y ago
    > But hypothetically, you could conceive of a disease with a high R value that is asymptomatic for the first month or two, and deadly in month three. Why hypothetically? HIV has historically had an insanely high R value (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880255/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880255/), delayed fatal severity - and a CFR of nearly 100%. We are lucky we have medication now, after 40 years and somewhat 35 million lives lost to that disease.
- dnautics 5y ago
  it doesn't have to be the case, but it often seems to be the case. I think there is a model by which deadliness is usually due to an accident -- note that most contemporary deadly pandemic diseases (even flu!) jump from animals to humans, so the deadliness is "accidental" in some sense, it's less deadly in the animal reservoir. But maybe the better way to think of it is entropically/random walk POV. Starting from a base sequence S0, if the virus starts out at a local maximum of deadliness (or at least an increase in deadliness that only has certain mechanistic "channels of escape"), and then optimizes strictly for contagiousness, statistically speaking most mutations in an S1 will make it less deadly (even if marginally so), unless contagiousness and deadliness are mechanistically linked. I think our understanding now is that the first order bottleneck in deadliness is something like "binding to a receptor", so most increases in contagiousness will have a strictly neutral-to-deleterious effect on deadliness.
- mro_name 5y ago
  > I don't believe there's any molecular mechanism why does it have to be molecular and not just evolutionary? That's what a virus does for a living after all.
  - azangru 5y ago
    I would say it's molecular biology that investigates what the virus actually does; while evolutionary biology is an attempt of explaining, mostly retrospectively, how an organism has changed over time, and possibly what has driven this change. My understanding is that evolutionary biology is kinda like statistics in the sense that it can tell you the distribution of the outcomes of tossing a coin, but it can't tell you whether the next flip of the coin will be the heads or the tails. And what we are usually most concerned about practically is not how the virus will behave over a long period of time, but what the outcome of the next flip will be.
    - mro_name 5y ago
      ah, I see. If you mean looking at the molecule's behaviour rather than the at molecule itself, we agree. I didn't mean evolutionary biology but the evolution of the virus, it's adaption to the host and change over time.
dragontamer 5y ago
Delta managed to thread the needle and grow both more deadly and have higher transmission. I'm sure some variant in the future will improve both deadliness and transmission. But there is a low chance that this variant (or any particular variant in general) will accomplish this feat.
- tomtheelder 5y ago
  Is Delta more deadly? I thought that was not really believed to be the case any more, just that it is much more transmissible. I could totally be wrong though; it's hard to find reliable info.
  - dragontamer 5y ago
    https://www.medicalnewstoday.com/articles/delta-variant-has-235-percent-higher-risk-of-icu-admission-than-original-virus https://www.medicalnewstoday.com/articles/delta-variant-has-... > However, the highest risks were from the Delta variant. In the Delta cases, there was a 108% increase in the risk of hospitalization, a 235% increased risk of ICU admission, and a 133% higher risk of death, compared with the original variant. Its very rare, but it does happen. Delta is proof of it. But chances are, we won't roll "snake eyes" again on the most recent mutation. Mutations are random: they can improve, or diminish the virus. Especially on something as important as the spike protein: that is literally the site that binds with our cells. Omicron could be better... or worse... at binding. There's all sorts of questions that are up in the air. From a policy / scientist point of view, it makes sense to "hope for the best, prepare for the worst". That is: we should react as if its a worst-case scenario mutation, but we need to keep hope until the proof actually comes in. ---- A lot of information will come in the next couple of weeks: I'm sure supercomputers are simulating how this molecule now interacts with our bodies (but those simulations take days or weeks to finish accurately). There are surely trials and science to be done here. Omnicron is a wakeup-call to the scientific community. But I'm not sure its worthy of being discussed in public yet. There's just not enough information here.
    - catlikesshrimp 5y ago

azangru 5y ago

> a researcher posted a comment here on HN where they said that virus deadliness and contagiousness were in tension. I've heard this statement a lot, and have been rather puzzled by why this must be the case. It's certainly true over a long period of time (a deadly pathogen that will kill off its hosts too quickly will also perish); and it's also certainly true that if a pathogen is very contagious but not deadly it can replace a deadly but less contagious variant; but I don't believe there's any molecular mechanism that locks these two properties relative to one another and dictates that if a new variant is more contagious it is likely to be less deadly and vice versa.

christophilus 5y ago
There is no such mechanism, from what I’ve read (not an expert). Most diseases demonstrate the tension for the reason you give: too deadly too fast reduces transmission rate. But hypothetically, you could conceive of a disease with a high R value that is asymptomatic for the first month or two, and deadly in month three.
- mschuster91 5y ago
  > But hypothetically, you could conceive of a disease with a high R value that is asymptomatic for the first month or two, and deadly in month three. Why hypothetically? HIV has historically had an insanely high R value (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880255/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880255/), delayed fatal severity - and a CFR of nearly 100%. We are lucky we have medication now, after 40 years and somewhat 35 million lives lost to that disease.
dnautics 5y ago
it doesn't have to be the case, but it often seems to be the case. I think there is a model by which deadliness is usually due to an accident -- note that most contemporary deadly pandemic diseases (even flu!) jump from animals to humans, so the deadliness is "accidental" in some sense, it's less deadly in the animal reservoir. But maybe the better way to think of it is entropically/random walk POV. Starting from a base sequence S0, if the virus starts out at a local maximum of deadliness (or at least an increase in deadliness that only has certain mechanistic "channels of escape"), and then optimizes strictly for contagiousness, statistically speaking most mutations in an S1 will make it less deadly (even if marginally so), unless contagiousness and deadliness are mechanistically linked. I think our understanding now is that the first order bottleneck in deadliness is something like "binding to a receptor", so most increases in contagiousness will have a strictly neutral-to-deleterious effect on deadliness.
mro_name 5y ago
> I don't believe there's any molecular mechanism why does it have to be molecular and not just evolutionary? That's what a virus does for a living after all.
- azangru 5y ago
  I would say it's molecular biology that investigates what the virus actually does; while evolutionary biology is an attempt of explaining, mostly retrospectively, how an organism has changed over time, and possibly what has driven this change. My understanding is that evolutionary biology is kinda like statistics in the sense that it can tell you the distribution of the outcomes of tossing a coin, but it can't tell you whether the next flip of the coin will be the heads or the tails. And what we are usually most concerned about practically is not how the virus will behave over a long period of time, but what the outcome of the next flip will be.
  - mro_name 5y ago
    ah, I see. If you mean looking at the molecule's behaviour rather than the at molecule itself, we agree. I didn't mean evolutionary biology but the evolution of the virus, it's adaption to the host and change over time.

dragontamer 5y ago

Delta managed to thread the needle and grow both more deadly and have higher transmission. I'm sure some variant in the future will improve both deadliness and transmission. But there is a low chance that this variant (or any particular variant in general) will accomplish this feat.

tomtheelder 5y ago
Is Delta more deadly? I thought that was not really believed to be the case any more, just that it is much more transmissible. I could totally be wrong though; it's hard to find reliable info.
- dragontamer 5y ago
  https://www.medicalnewstoday.com/articles/delta-variant-has-235-percent-higher-risk-of-icu-admission-than-original-virus https://www.medicalnewstoday.com/articles/delta-variant-has-... > However, the highest risks were from the Delta variant. In the Delta cases, there was a 108% increase in the risk of hospitalization, a 235% increased risk of ICU admission, and a 133% higher risk of death, compared with the original variant. Its very rare, but it does happen. Delta is proof of it. But chances are, we won't roll "snake eyes" again on the most recent mutation. Mutations are random: they can improve, or diminish the virus. Especially on something as important as the spike protein: that is literally the site that binds with our cells. Omicron could be better... or worse... at binding. There's all sorts of questions that are up in the air. From a policy / scientist point of view, it makes sense to "hope for the best, prepare for the worst". That is: we should react as if its a worst-case scenario mutation, but we need to keep hope until the proof actually comes in. ---- A lot of information will come in the next couple of weeks: I'm sure supercomputers are simulating how this molecule now interacts with our bodies (but those simulations take days or weeks to finish accurately). There are surely trials and science to be done here. Omnicron is a wakeup-call to the scientific community. But I'm not sure its worthy of being discussed in public yet. There's just not enough information here.
  - catlikesshrimp 5y ago