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Nobody seems to be talking about the actual reason Chinese doctors found chloroquine (and HCQ) interesting and it has nothing to do with it's immunosuppressing

Nobody seems to be talking about the actual reason Chinese doctors found chloroquine (and HCQ) interesting and it has nothing to do with it's immunosuppressing effect: 1) Chloroquine (and HCQ) is a zinc ionophore: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/ 2) Zinc seems to inhibit RNA polymerase of Coronaviruses in vitro https://www.researchgate.net/publication/47794995_Zn_Inhibits_Coronavirus_and_Arterivirus_RNA_Polymerase_Activity_In_Vitro_and_Zinc_Ionophores_Block_the_Replication_of_These_Viruses_in_Cell_Culture https://www.researchgate.net/publication/47794995_Zn_Inhibit... Their conclusion was that chloroquine could indeed allow zinc to enter the cell and then inhibit replication (and therefore that the treatment needed to be administered early). Nobody seems to be talking about a very easy way to verify chloroquine (and HCQ) efficiency by just using the same method used in China: Cross-check the list of patients infected with Lupus (lupus erythematosus) and with chronic HCQ treatment (they take it for years) with the list of known infected COVID19 patients. In China (and specifically in Wuhan), this is how they (team of Dr Zhang Zhan) found out about the efficiency of HCQ. They noticed that there were no patients with chronic HCQ treatment for lupus (lupus erythematosus) infected with covid19. This was in peoples Hospital of Wuhan University (source: https://www.jqknews.com/news/388543-The_novel_coronavirus_pneumonia_has_short_term_curative_effect_on_the_treatment_of_new_crown_pneumonia.html https://www.jqknews.com/news/388543-The_novel_coronavirus_pn...) This alone would be enough to prove some efficiency even as prophyalxis (as they are advocating officially in India). This should be quite trivial to check with the current amount of confirmed infection. These details were all explained in this medcram vid: https://www.youtube.com/watch?v=Eeh054-Hx1U https://www.youtube.com/watch?v=Eeh054-Hx1U

nradov 7y ago
In principle that would be a great thing to check but due to lack of clinical systems interoperability it's not at all trivial to check. Surescripts and the various pharmacy chains have data on who has been taking chloroquine but researchers will still have to get access, and then do a bunch of record linkage work to compare outcomes. In the hardest hit areas I suspect healthcare providers have also fallen behind on data entry so there's going to be a data quality problem.
- Cantbekhan 7y ago
  Yes ... And it seems this issue is a global one. We seem to have the ability to put half the world in lockdowns but we don't have ability to crosscheck a bunch of different patient databases that could already contain the answer to this whole HCQ debate.
- viggity 7y ago
  Korea has released all of their data and I think this is possible to cross check https://hira-covid19.net/ https://hira-covid19.net/
  - Cantbekhan 7y ago
    It's not open registration tho ... I tried and it needs "admin confirmation" and I'm not sure the data is in English which would make this rather "complicated" for a non-Korean. I'm also not sure they'll give out all patient detailed history but we'll see...
majormajor 7y ago
> Their conclusion was that chloroquine could indeed allow zinc to enter the cell and then inhibit replication (and therefore that the treatment needed to be administered early). Where does the "if it inhibits replication it needs to be administered early" line come from? I've seen it elsewhere too, but why wouldn't inhibit replication lead to => continually declining amounts in the body => easier recovery at any stage?
- giardini 7y ago
  Yes, reducing viral replication at any time would make recovery easier. But if the virus replicates sufficiently before chloroquine + zinc is administered then much damage is already done. So it's a race between the virus and the "cure". Get the "cure" in quickly and the virus stops replication before much harm occurs; get the "cure" in late and the virus has run most of its course and maximal damage is done. Also, since the viral damage opens the door to opportunistic bacterial infections (e.g., pneumonia), antibiotics may be given to prevent bacteria from taking hold.
  - Cantbekhan 7y ago
    Which might be the reason some countries such as India decided to advise HCQ as prophylaxis for healthcare personnel, Source: https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophylaxisforSARSCoV2infection.pdf https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloro...
    - 3fe9a03ccd14ca5 7y ago
      We should be doing the same here as well. Unfortunate HCQ has suddenly become some political casualty in our hyper polarized world.
- Cantbekhan 7y ago
  Because they didn't intend to use chloroquine as a way to reduce the immune response to cytokine storms. They intended to use it to prevent virus replication in the cells at the early stages of the immune response to allow the immune system to build up a response at a slower pace. The amount of treatment proposed in Europe is around 5 days of HCQ with about 800mg on D1 and then 400mg on D2-5. This is an incredibly low dosage and will have very little immunosuppressant effect. It takes a very long time to act as an efficient immunosuppressant (1 to 3 months for Lupus). Expecting HCQ to suppress the immune system for cytokine storms in a matter of hours seems very strange. As that controversial French doctor said in multiple interviews. If you are already in need of a respirator then your issue is no longer the virus but your own immune system killing you (cytokine storm or added bacterial pneumonia). At that stage, HCQ is not very useful. Not in these dosages at least. Most people are only focusing on the immunosuppressing effect of HCQ for some reason which is very strange to me. It takes time for chloroquine to act as a zinc ionophore as well and for zinc to enter the cells (and it needs to be in the cells to inhibit RNA polymerase). As you can see in the studies I posted. Between 24 and 72 hours it seems. If the virus cannot replicate correctly (with the zinc idea), it might give more time to "flatten the curve" for the immune system. To build up antibodies and respond to the disease without inducing a cytokine storm. This at least is their hypothesis. And it has not been confirmed in any other way than by observing that those with chronic Lupus+HCQ treatment seemed to be "immune" to the disease. And this was only done in Wuhan as far as I know. Unfortunately Dr Zhan Zhang has not yet published his full results except for this preliminary https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2.full.pdf https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v... Which doesn't go into much detail about anything except that "it seems to work". Unfortunately ... Yet I do see logic in the idea. I just wish people (with access to patient files in major hospital centers) would also look into this and they could maybe confirm this "once and for all" without even needing a full blown trial.
deleted 7y ago
[deleted]
ruggi 7y ago
An interesting hint could come from this pre-print study: https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 They tried different administration modalities of HCQ to in-vitro infected cells: some cells got nothing (control), some got HCQ only before infection, some got HCQ only after infection, some got HCQ both before and after infection. THe cells that got HCQ only before or only after infection had just slightly better outcome than control (they appear as heavily infected), while cells that received HCQ both before and after contagion were in much healthier conditions. If that would be the same in vivo as in vitro, that would entail that it would be possible to use HCQ as prophylaxis, given that the patients never stop taking the drug. Of course the caveat is "IF that would be the same in vivo as in vitro", that they didn't (yet) tested.

nradov 7y ago

In principle that would be a great thing to check but due to lack of clinical systems interoperability it's not at all trivial to check. Surescripts and the various pharmacy chains have data on who has been taking chloroquine but researchers will still have to get access, and then do a bunch of record linkage work to compare outcomes. In the hardest hit areas I suspect healthcare providers have also fallen behind on data entry so there's going to be a data quality problem.

Cantbekhan 7y ago
Yes ... And it seems this issue is a global one. We seem to have the ability to put half the world in lockdowns but we don't have ability to crosscheck a bunch of different patient databases that could already contain the answer to this whole HCQ debate.
viggity 7y ago
Korea has released all of their data and I think this is possible to cross check https://hira-covid19.net/ https://hira-covid19.net/
- Cantbekhan 7y ago
  It's not open registration tho ... I tried and it needs "admin confirmation" and I'm not sure the data is in English which would make this rather "complicated" for a non-Korean. I'm also not sure they'll give out all patient detailed history but we'll see...

majormajor 7y ago

> Their conclusion was that chloroquine could indeed allow zinc to enter the cell and then inhibit replication (and therefore that the treatment needed to be administered early). Where does the "if it inhibits replication it needs to be administered early" line come from? I've seen it elsewhere too, but why wouldn't inhibit replication lead to => continually declining amounts in the body => easier recovery at any stage?

giardini 7y ago
Yes, reducing viral replication at any time would make recovery easier. But if the virus replicates sufficiently before chloroquine + zinc is administered then much damage is already done. So it's a race between the virus and the "cure". Get the "cure" in quickly and the virus stops replication before much harm occurs; get the "cure" in late and the virus has run most of its course and maximal damage is done. Also, since the viral damage opens the door to opportunistic bacterial infections (e.g., pneumonia), antibiotics may be given to prevent bacteria from taking hold.
- Cantbekhan 7y ago
  Which might be the reason some countries such as India decided to advise HCQ as prophylaxis for healthcare personnel, Source: https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophylaxisforSARSCoV2infection.pdf https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloro...
  - 3fe9a03ccd14ca5 7y ago
    We should be doing the same here as well. Unfortunate HCQ has suddenly become some political casualty in our hyper polarized world.
Cantbekhan 7y ago
Because they didn't intend to use chloroquine as a way to reduce the immune response to cytokine storms. They intended to use it to prevent virus replication in the cells at the early stages of the immune response to allow the immune system to build up a response at a slower pace. The amount of treatment proposed in Europe is around 5 days of HCQ with about 800mg on D1 and then 400mg on D2-5. This is an incredibly low dosage and will have very little immunosuppressant effect. It takes a very long time to act as an efficient immunosuppressant (1 to 3 months for Lupus). Expecting HCQ to suppress the immune system for cytokine storms in a matter of hours seems very strange. As that controversial French doctor said in multiple interviews. If you are already in need of a respirator then your issue is no longer the virus but your own immune system killing you (cytokine storm or added bacterial pneumonia). At that stage, HCQ is not very useful. Not in these dosages at least. Most people are only focusing on the immunosuppressing effect of HCQ for some reason which is very strange to me. It takes time for chloroquine to act as a zinc ionophore as well and for zinc to enter the cells (and it needs to be in the cells to inhibit RNA polymerase). As you can see in the studies I posted. Between 24 and 72 hours it seems. If the virus cannot replicate correctly (with the zinc idea), it might give more time to "flatten the curve" for the immune system. To build up antibodies and respond to the disease without inducing a cytokine storm. This at least is their hypothesis. And it has not been confirmed in any other way than by observing that those with chronic Lupus+HCQ treatment seemed to be "immune" to the disease. And this was only done in Wuhan as far as I know. Unfortunately Dr Zhan Zhang has not yet published his full results except for this preliminary https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v2.full.pdf https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v... Which doesn't go into much detail about anything except that "it seems to work". Unfortunately ... Yet I do see logic in the idea. I just wish people (with access to patient files in major hospital centers) would also look into this and they could maybe confirm this "once and for all" without even needing a full blown trial.

deleted 7y ago

[deleted]

ruggi 7y ago

An interesting hint could come from this pre-print study: https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 https://www.biorxiv.org/content/10.1101/2020.03.29.014407v1 They tried different administration modalities of HCQ to in-vitro infected cells: some cells got nothing (control), some got HCQ only before infection, some got HCQ only after infection, some got HCQ both before and after infection. THe cells that got HCQ only before or only after infection had just slightly better outcome than control (they appear as heavily infected), while cells that received HCQ both before and after contagion were in much healthier conditions. If that would be the same in vivo as in vitro, that would entail that it would be possible to use HCQ as prophylaxis, given that the patients never stop taking the drug. Of course the caveat is "IF that would be the same in vivo as in vitro", that they didn't (yet) tested.