5 ms·

A really excellent review, published today, of the current state of knowledge on HCQ: https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroqui

A really excellent review, published today, of the current state of knowledge on HCQ: https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6 https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hy... Note this is by Derek Lowe of "Things I won't work with" fame, an extremely informative series about entertainingly dangerous chemicals. And here's a new piece of candy for people who want to get their hopes up about a promising treatment: https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883 https://stm.sciencemag.org/content/early/2020/04/03/scitrans... (h/t Helen Branswell of STAT news, who is very much worth following, who retweeted Timothy Sheahan)

dang 7y ago
That review article was posted at https://news.ycombinator.com/item?id=22794850 https://news.ycombinator.com/item?id=22794850. We'll put it in the second-chance pool (https://news.ycombinator.com/item?id=11662380 https://news.ycombinator.com/item?id=11662380), so it will get a random placement on HN's front page. Thanks!
deleted 7y ago
[deleted]
robocat 7y ago
> a promising treatment https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883 https://stm.sciencemag.org/content/early/2020/04/03/scitrans... That is frightening. Increasing the mutation rate must carry a large unknown risk. Also surely the first thing to mutate will be self-defeating resistance to that drug...
- raphlinus 7y ago
  The thought occurred to me as well, I got a strong sense of "playing with fire." However, viruses have a very high mutation rate as it is [1], so I'm not sure how much difference it makes. Btw, one of the best markers for overconfident but uninformed analysis is overinterpreting the fact that we have all these strains of SARS-CoV-2 as suggesting they have different degrees of infectiousness or health impacts. Certainly the different flu strains do, and, thanks to fine-grained sequencing efforts (Nextstrain in particular is doing awesome work) we can see lots of strains of this one, but Trevor Bedford has estimated that we have about a year or more before the variation in strains has an impact other than being able to "fingerprint" the chains of transmission. [1]: https://jvi.asm.org/content/92/14/e01031-17 https://jvi.asm.org/content/92/14/e01031-17
  - robocat 7y ago
    I would have thought any variation that has a significantly increased transmission rate should dominate within time. Detecting small differences in effects between different genetic variants of the virus would require large statistical populations, and wide testing for the different genetic variants. Without that, Trevor is only making an educated guess?
    - raphlinus 7y ago
      I'm not qualified to say either way, but here's the relevant thread: https://twitter.com/trvrb/status/1244750382338719745 https://twitter.com/trvrb/status/1244750382338719745 Also, for people who don't know, Trevor is arguably the single most expert person in the world to weigh in on this. And here's the specific thread where he predicts it will take a few years for the virus to mutate enough to significantly hinder a vaccine: https://twitter.com/trvrb/status/1242628550563250176 https://twitter.com/trvrb/status/1242628550563250176
      - robocat 7y ago
        Awesome thanks. Trevor Bedford‘s key comments: “There have been only 11 mutations to proteins that are widely distributed. These are potentially functionally distinct variants that deserve attention and experimental and clinical follow up. But my expectation would be most have ‘little effect’ without further data“. “in terms of immunity, there is a single widely circulating mutation in spike protein (D614G). Spike is present on the surface of the virus and is what the immune system sees“ “If you follow a transmission chain in which one person with flu infects another person and they infect another person and so on, you'll find that the virus mutates about once every 10 days across its genome. Almost all of these mutations will have little to no effect on virus function. Evolution weeds out the mutations that ‘break’ the virus and mutations that make a virus replicate better are extremely rare.” The effects of the OP drug increasing the mutation rate would need to be modelled to understand risks.
  - robocat 7y ago
    Here is a paper which suggests they found a different strain: https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.... “In this report we describe the first major evolutionary event of the SARS-CoV-2 virus following its emergence into the human population. Although the biological consequences of this deletion remain unknown, the alteration of the N gene transcription would suggest this may have an impact on virus phenotype.“ However they don’t speculate on whether that strain is more likely to spread (it clearly is a viable mutation).

dang 7y ago

That review article was posted at https://news.ycombinator.com/item?id=22794850 https://news.ycombinator.com/item?id=22794850. We'll put it in the second-chance pool (https://news.ycombinator.com/item?id=11662380 https://news.ycombinator.com/item?id=11662380), so it will get a random placement on HN's front page. Thanks!

deleted 7y ago

[deleted]

robocat 7y ago

> a promising treatment https://stm.sciencemag.org/content/early/2020/04/03/scitranslmed.abb5883 https://stm.sciencemag.org/content/early/2020/04/03/scitrans... That is frightening. Increasing the mutation rate must carry a large unknown risk. Also surely the first thing to mutate will be self-defeating resistance to that drug...

raphlinus 7y ago
The thought occurred to me as well, I got a strong sense of "playing with fire." However, viruses have a very high mutation rate as it is [1], so I'm not sure how much difference it makes. Btw, one of the best markers for overconfident but uninformed analysis is overinterpreting the fact that we have all these strains of SARS-CoV-2 as suggesting they have different degrees of infectiousness or health impacts. Certainly the different flu strains do, and, thanks to fine-grained sequencing efforts (Nextstrain in particular is doing awesome work) we can see lots of strains of this one, but Trevor Bedford has estimated that we have about a year or more before the variation in strains has an impact other than being able to "fingerprint" the chains of transmission. [1]: https://jvi.asm.org/content/92/14/e01031-17 https://jvi.asm.org/content/92/14/e01031-17
- robocat 7y ago
  I would have thought any variation that has a significantly increased transmission rate should dominate within time. Detecting small differences in effects between different genetic variants of the virus would require large statistical populations, and wide testing for the different genetic variants. Without that, Trevor is only making an educated guess?
  - raphlinus 7y ago
    I'm not qualified to say either way, but here's the relevant thread: https://twitter.com/trvrb/status/1244750382338719745 https://twitter.com/trvrb/status/1244750382338719745 Also, for people who don't know, Trevor is arguably the single most expert person in the world to weigh in on this. And here's the specific thread where he predicts it will take a few years for the virus to mutate enough to significantly hinder a vaccine: https://twitter.com/trvrb/status/1242628550563250176 https://twitter.com/trvrb/status/1242628550563250176
    - robocat 7y ago
      Awesome thanks. Trevor Bedford‘s key comments: “There have been only 11 mutations to proteins that are widely distributed. These are potentially functionally distinct variants that deserve attention and experimental and clinical follow up. But my expectation would be most have ‘little effect’ without further data“. “in terms of immunity, there is a single widely circulating mutation in spike protein (D614G). Spike is present on the surface of the virus and is what the immune system sees“ “If you follow a transmission chain in which one person with flu infects another person and they infect another person and so on, you'll find that the virus mutates about once every 10 days across its genome. Almost all of these mutations will have little to no effect on virus function. Evolution weeds out the mutations that ‘break’ the virus and mutations that make a virus replicate better are extremely rare.” The effects of the OP drug increasing the mutation rate would need to be modelled to understand risks.
- robocat 7y ago
  Here is a paper which suggests they found a different strain: https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.full.pdf https://www.biorxiv.org/content/10.1101/2020.03.11.987222v1.... “In this report we describe the first major evolutionary event of the SARS-CoV-2 virus following its emergence into the human population. Although the biological consequences of this deletion remain unknown, the alteration of the N gene transcription would suggest this may have an impact on virus phenotype.“ However they don’t speculate on whether that strain is more likely to spread (it clearly is a viable mutation).