3 ms·

One of the issues with the study is that they didn't use the clinical outcome as an endpoint, they just measured the virus concentration in the throat (and even

One of the issues with the study is that they didn't use the clinical outcome as an endpoint, they just measured the virus concentration in the throat (and even that not properly for all cases as far as this HN post says). Huge effect size doesn't matter at all when the effect is not the correct one. There is a significant risk that this surrogate endpoint is not telling the true story as the virus migrates to the lung, measuring in the throat could be very misleading.

ekianjo 7y ago
Is there a reason to believe the viral load in the throat and the lungs would not follow the same trend? And you also forget to mention this (CQ and HCQ concentrate in certain organs): > It has been reported that oral absorption of CQ and HCQ in humans is very efficient. In animals, both drugs share similar tissue distribution patterns, with high concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma10. It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans11. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection. https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0
- fabian2k 7y ago
  Yes, that's one aspect discussed in the podcast with Christian Drosten that is linked in the blog post. This is the relevant part: > We have a lot of experience. We have made the most precise description of an untreated patient cohort among the Munich patients. And at the Munich group, we saw how the virus concentration in both the throat and lungs behaved over time. And we can say that at the beginning of the disease the virus is in the throat and it goes away on its own through the - let's say - the first ten days of the disease. After that, many patients in the throat have little or only irregular evidence of the virus. But that has nothing to do with how the virus behaves in the lungs. The virus is then really replicative in the lungs, especially in severe cases. And we can also say what the patient has in his throat, it has nothing to do with how the clinical development of the disease continues, whether the patient quickly gets well or only goes through a difficult phase. So what is being measured in this entire clinical study has nothing to do with the outcome of the disease, with the symptoms, but is only an initial indicator of how the disease starts. For all patients, the virus concentration drops in the first week, but if you now imagine that the group being treated will be included a little later and the untreated group being included earlier in this study, it is in nature the thing that with this group that was later included - they are already further in eliminating the virus from the throat - that the virus then goes down in the throat, faster. This disappears faster because they have simply been in the course of the disease for a long time. Whether this is due to the fact that they are treated, cannot be said at all from this entire study. Perhaps it would have been so if the groups had been put together as here, but if they hadn't given them chloroquine, but some headache pill, the study would have been the same.
- DanBC 7y ago
  Yes. They do testing and it returns negative, and then they wash the lungs out and that returns positive. https://twitter.com/keirshiels/status/1241042704966070272 https://twitter.com/keirshiels/status/1241042704966070272
dx034 7y ago
Reducing viral load in the throat would make it less contagious though? In that case, wouldn't it be suitable to use for patients that are likely infected but don't need hospital treatment to reduce chances they'll infect others while quarantined?
choeger 7y ago
Now here's the thing. Anyone with a basic understanding of probabilities could understand how to fake a study by doing just that. If I measure enough potentially interesting points over a small group of individuals, I will quite likely get at least one interesting correlation (aka, "drinking one glass of vodka a day helps to lose weight!"). But did anyone of the critics of that study ever try to do a follow-up? Did a single science journalist call the group and ask them about that study? How many measurements did they make? How did they actually chose the patients? Did these patients actually recover?

ekianjo 7y ago

Is there a reason to believe the viral load in the throat and the lungs would not follow the same trend? And you also forget to mention this (CQ and HCQ concentrate in certain organs): > It has been reported that oral absorption of CQ and HCQ in humans is very efficient. In animals, both drugs share similar tissue distribution patterns, with high concentrations in the liver, spleen, kidney, and lung reaching levels of 200–700 times higher than those in the plasma10. It was reported that safe dosage (6–6.5 mg/kg per day) of HCQ sulfate could generate serum levels of 1.4–1.5 μM in humans11. Therefore, with a safe dosage, HCQ concentration in the above tissues is likely to be achieved to inhibit SARS-CoV-2 infection. https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0

fabian2k 7y ago
Yes, that's one aspect discussed in the podcast with Christian Drosten that is linked in the blog post. This is the relevant part: > We have a lot of experience. We have made the most precise description of an untreated patient cohort among the Munich patients. And at the Munich group, we saw how the virus concentration in both the throat and lungs behaved over time. And we can say that at the beginning of the disease the virus is in the throat and it goes away on its own through the - let's say - the first ten days of the disease. After that, many patients in the throat have little or only irregular evidence of the virus. But that has nothing to do with how the virus behaves in the lungs. The virus is then really replicative in the lungs, especially in severe cases. And we can also say what the patient has in his throat, it has nothing to do with how the clinical development of the disease continues, whether the patient quickly gets well or only goes through a difficult phase. So what is being measured in this entire clinical study has nothing to do with the outcome of the disease, with the symptoms, but is only an initial indicator of how the disease starts. For all patients, the virus concentration drops in the first week, but if you now imagine that the group being treated will be included a little later and the untreated group being included earlier in this study, it is in nature the thing that with this group that was later included - they are already further in eliminating the virus from the throat - that the virus then goes down in the throat, faster. This disappears faster because they have simply been in the course of the disease for a long time. Whether this is due to the fact that they are treated, cannot be said at all from this entire study. Perhaps it would have been so if the groups had been put together as here, but if they hadn't given them chloroquine, but some headache pill, the study would have been the same.
DanBC 7y ago
Yes. They do testing and it returns negative, and then they wash the lungs out and that returns positive. https://twitter.com/keirshiels/status/1241042704966070272 https://twitter.com/keirshiels/status/1241042704966070272

dx034 7y ago

Reducing viral load in the throat would make it less contagious though? In that case, wouldn't it be suitable to use for patients that are likely infected but don't need hospital treatment to reduce chances they'll infect others while quarantined?

choeger 7y ago

Now here's the thing. Anyone with a basic understanding of probabilities could understand how to fake a study by doing just that. If I measure enough potentially interesting points over a small group of individuals, I will quite likely get at least one interesting correlation (aka, "drinking one glass of vodka a day helps to lose weight!"). But did anyone of the critics of that study ever try to do a follow-up? Did a single science journalist call the group and ask them about that study? How many measurements did they make? How did they actually chose the patients? Did these patients actually recover?