4 ms·

Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin),

Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin), that's why the discussion won't stop. Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that. EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).

mxcrossb 6y ago
It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. Such a large percentage of people recover on their own that even a very effective drug has limited returns. And of course you need the infrastructure to detect the disease early and deliver huge supplies. It makes me worry that all antivirals we try will fail.
- lbeltrame 6y ago
  > It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. This is the same for remedisivir, and also for ritonavir/lopinavir/ribavirin: they must be given within 7 days of symptom onset to be effective. In fact, the latter was deemed unsuccesful in a first paper, because it was given late, then it was reconsidered when given earlier during the disease. This is not surprising, given how the disease works (outlined also by the Cell paper from yesterday): at some point the consequences of the highly altered inflammatory reaction greatly surpass the effects of the replication of the virus itself. This calls more for extensive and early testing, IMO.
  - ceejayoz 6y ago
    Remdesivir doesn't have the sudden cardiac death side effect, though, does it? HCQ's issue may be a bad combination of "has to be taken early" and "has significant side effects".
    - ytNumbers 6y ago
      HCQ has been around for 70 years. Remdesivir's issue is that everyone gets to be the guinea pig. Sometimes it's better to go with the devil you know.
      - ceejayoz 6y ago
        > HCQ has been around for 70 years. Not in an antiviral context, and certainly not for SARS-CoV-2.
        dpoochieni 6y ago
        So? The point here is the safety of it, plus there's research going back to 2006 about its effectiveness for other Coronaviruses. I mean do whatever you want to do, but there's a reason most people in government are taking it. In my country they privately take it, while publicly not endorsing it to prevent shortages
        DanBC 6y ago
        > The point here is the safety of it Yes, which is why all of the studies keep saying that it's too dangerous to use as treatment for covid-19.
        lbeltrame 6y ago
        Too dangerous (or even ineffective) to use it with patients with severe COVID-19. Whether it may be the same or not in a prophylaxis regime or for outpatient use (mild to moderate that does not require hospitalization) is yet unknown at this point (most papers that I've read are on hospitalized patients). It may be too toxic, it may not cause a noticeable effect, but currently it is a big question mark.
        DanBC 6y ago
        You'd take the risk for people with severe Covid-19 because it might[1] save their life. You can't justify taking that risk in other people because they're probably not going to be killed by covid-19. Balancing harm from medication against not much harm from covid comes out against the meds. [1] Except now we know (and we always thought this) that it won't save their life; it'll increase their risk of death.
  - sp332 6y ago
    https://arstechnica.com/science/2020/05/the-antiviral-remdesivir-shortens-covid-19-recovery-times-study-shows/ https://arstechnica.com/science/2020/05/the-antiviral-remdes... participants who entered the trial more than 10 days after the onset of symptoms actually showed a better response to remdesivir than those who started being treated during the first 10 days of being symptomatic. It's not a huge improvement, but it doesn't seem to be too dependent on starting treatment early.
- cm2187 6y ago
  Agree but the rationale is that you reduce the contamination by testing people early and giving them drugs that reduce the viral charge, hence the contagiousness.
Yoric 6y ago
> Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. To be fair, Didier Raoult has changed his own claims several times (including dosage, drug mix and he even switched from chloroquine to hydroxychloroquine – afait, these are different molecules). Including after the studies were started. This doesn't mean that he's wrong, but at this stage, there are so many red flags that it's hard to take anything he said seriously.
- marvin 6y ago
  For the purposes we're discussing here, Raoult et al. are front-line clinicians working to save lives under extreme uncertainty, with every decision scrutinized with the benefit of hindsight. You shouldn't hold them to the same standard as pure research scientists. Research scientists have all the time in the world, clinicians don't. Once again, it's a peacetime army of bureaucrats vs. an unknown enemy that doesn't have the decency to wait for understanding to catch up with reality. Decisions have to be made with an imperfect understanding, in a reality that changes every day. The truth will seem obvious afterwards, but right now it doesn't. Those not on the front lines should keep to their very important job of improving prospects for the future, and keep the judgement out of it.

mxcrossb 6y ago

It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. Such a large percentage of people recover on their own that even a very effective drug has limited returns. And of course you need the infrastructure to detect the disease early and deliver huge supplies. It makes me worry that all antivirals we try will fail.

lbeltrame 6y ago
> It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. This is the same for remedisivir, and also for ritonavir/lopinavir/ribavirin: they must be given within 7 days of symptom onset to be effective. In fact, the latter was deemed unsuccesful in a first paper, because it was given late, then it was reconsidered when given earlier during the disease. This is not surprising, given how the disease works (outlined also by the Cell paper from yesterday): at some point the consequences of the highly altered inflammatory reaction greatly surpass the effects of the replication of the virus itself. This calls more for extensive and early testing, IMO.
- ceejayoz 6y ago
  Remdesivir doesn't have the sudden cardiac death side effect, though, does it? HCQ's issue may be a bad combination of "has to be taken early" and "has significant side effects".
  - ytNumbers 6y ago
    HCQ has been around for 70 years. Remdesivir's issue is that everyone gets to be the guinea pig. Sometimes it's better to go with the devil you know.
    - ceejayoz 6y ago
      > HCQ has been around for 70 years. Not in an antiviral context, and certainly not for SARS-CoV-2.
      - dpoochieni 6y ago
        So? The point here is the safety of it, plus there's research going back to 2006 about its effectiveness for other Coronaviruses. I mean do whatever you want to do, but there's a reason most people in government are taking it. In my country they privately take it, while publicly not endorsing it to prevent shortages
        DanBC 6y ago
        > The point here is the safety of it Yes, which is why all of the studies keep saying that it's too dangerous to use as treatment for covid-19.
        lbeltrame 6y ago
        Too dangerous (or even ineffective) to use it with patients with severe COVID-19. Whether it may be the same or not in a prophylaxis regime or for outpatient use (mild to moderate that does not require hospitalization) is yet unknown at this point (most papers that I've read are on hospitalized patients). It may be too toxic, it may not cause a noticeable effect, but currently it is a big question mark.
        DanBC 6y ago
        You'd take the risk for people with severe Covid-19 because it might[1] save their life. You can't justify taking that risk in other people because they're probably not going to be killed by covid-19. Balancing harm from medication against not much harm from covid comes out against the meds. [1] Except now we know (and we always thought this) that it won't save their life; it'll increase their risk of death.
- sp332 6y ago
  https://arstechnica.com/science/2020/05/the-antiviral-remdesivir-shortens-covid-19-recovery-times-study-shows/ https://arstechnica.com/science/2020/05/the-antiviral-remdes... participants who entered the trial more than 10 days after the onset of symptoms actually showed a better response to remdesivir than those who started being treated during the first 10 days of being symptomatic. It's not a huge improvement, but it doesn't seem to be too dependent on starting treatment early.
cm2187 6y ago
Agree but the rationale is that you reduce the contamination by testing people early and giving them drugs that reduce the viral charge, hence the contagiousness.

Yoric 6y ago

> Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. To be fair, Didier Raoult has changed his own claims several times (including dosage, drug mix and he even switched from chloroquine to hydroxychloroquine – afait, these are different molecules). Including after the studies were started. This doesn't mean that he's wrong, but at this stage, there are so many red flags that it's hard to take anything he said seriously.

marvin 6y ago
For the purposes we're discussing here, Raoult et al. are front-line clinicians working to save lives under extreme uncertainty, with every decision scrutinized with the benefit of hindsight. You shouldn't hold them to the same standard as pure research scientists. Research scientists have all the time in the world, clinicians don't. Once again, it's a peacetime army of bureaucrats vs. an unknown enemy that doesn't have the decency to wait for understanding to catch up with reality. Decisions have to be made with an imperfect understanding, in a reality that changes every day. The truth will seem obvious afterwards, but right now it doesn't. Those not on the front lines should keep to their very important job of improving prospects for the future, and keep the judgement out of it.