6 ms·

> so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late What's the mechanism supposed to be here? If it suppres

> so if it turns out that HCQ is effective but that by the time patients are hospitalized it's too late What's the mechanism supposed to be here? If it suppresses replication of the virus, shouldn't that be effective up to close to the point of death - once replication is slowed enough, viral load should fall off, and recovery should happen?

anoncareer0212 7y ago
Hydroxycholorquine is an immunosuppresant not an anti-viral, so the theory here is the problem isn't the virus, but reacting to it. It's not quite as silly as it sounds - this does, rarely, work, specifically with malaria. But, it is pretty silly when you contrast the likelihood of it being a meaningful thereapeutic versus the significance it's taken on
- edoo 7y ago
  From my understanding it does something to the virus membrane which then allows a high dose of zinc to actually disrupt the virus. I think the antibiotic component is to suppress risk of a secondary infection due to the suppressant effect.
  - dTal 7y ago
    I have heard (provenance rating: "rumour") that it's only effective when taken in conjunction with zinc supplementation.
- jdkee 7y ago
  This is the popular origin of the hydroxycloroquine and zinc thesis. https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDInv_zLVFTgXA8tW0Mf1iiuuM_&index=36&t=0s https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDIn...
  - Gibbon1 7y ago
    Part of the reason I'm suspicious of hydroxycloroquine and zinc is because for decades zinc and cloroquine have been fringe quack medicine staples for treating/preventing colds and flu.
egl2020 7y ago
You might have accumulated too much damage or other failure modes might have kicked in.
DiogenesKynikos 7y ago
From what I understand, in the late stages of the disease, it's not necessarily the virus that's killing the patient. Often, the virus has been cleared and it's the patient's own immune response that's doing the damage.
- Mtinie 7y ago
  This matches what I've read, too. It's less about the virus during the later stages and more about the infected person's immune system. If they've entered a state of amplified immune response, colloquially called a "cytokine storm," organs are damaged when their cells are mistakenly attacked. If you can moderate the immune system's reaction you can prevent significant damage. HCQ is useful for this type of immuno-suppression. Here's a pre-print of an article from a few years back which talks about HCQ and cytokine storms: Scott W. Canna, Edward M. Behrens. Making Sense of the Cytokine Storm: a conceptual framework for understanding, diagnosing and treating hemophagocytic syndromes. Pediatric Clinics of North America [Preprint]. April 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368378/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368378/ Published article link: https://dx.doi.org/10.1016%2Fj.pcl.2012.03.002 https://dx.doi.org/10.1016%2Fj.pcl.2012.03.002
  - mundu_wa_hinya 7y ago
    The problem is that the immunosuppression by hcq takes a few weeks to kick in [1]. So it will not stop the Cytokine storm in time. tocilizumab seems to be a better option. 1. https://www.versusarthritis.org/about-arthritis/treatments/drugs/hydroxychloroquine/ https://www.versusarthritis.org/about-arthritis/treatments/d... 2. https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_In...
    - mariodiana 7y ago
      My understanding is that tocilizumab is roughly 100 times as expensive as hydroxychloroquine and has intensive storage requirements. I don't see how the drug scales.
apendleton 7y ago
There's some evidence now that viral load peaks in the first week, and it's the second week that tends to be a problem for people with very serious cases. By the time many of these patients are hospitalized, their viral load is already going down on its own, and their serious complications are either due to immune overreaction (the so-called "cytokine storm"), or some sort of opportunistic co-infection like bacterial pneumonia. It's decently likely from what I've been reading that there might end up being effective pharmaceuticals for each stage, but that they'll be totally different from one another: maybe HCQ and antivirals like remdesivir or favipiravir early, and maybe immune-modulators like tocilizumab or even corticosteroids in this second phase. But again, the devil will be in the details, as it looks like HCQ doesn't work late, and steroids or other immune modulators might be actively harmful in that first stage when the virus is still surging. As for mechanism: nobody is really sure. HCQ does have some immune-modulating effects (that's what makes it useful for lupus), but there's also speculation that it might have some effect on the interaction between the ACE2 receptor and the coronavirus spike protein, and so somehow inhibit viral entry (see, e.g., https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0).

anoncareer0212 7y ago

Hydroxycholorquine is an immunosuppresant not an anti-viral, so the theory here is the problem isn't the virus, but reacting to it. It's not quite as silly as it sounds - this does, rarely, work, specifically with malaria. But, it is pretty silly when you contrast the likelihood of it being a meaningful thereapeutic versus the significance it's taken on

edoo 7y ago
From my understanding it does something to the virus membrane which then allows a high dose of zinc to actually disrupt the virus. I think the antibiotic component is to suppress risk of a secondary infection due to the suppressant effect.
- dTal 7y ago
  I have heard (provenance rating: "rumour") that it's only effective when taken in conjunction with zinc supplementation.
jdkee 7y ago
This is the popular origin of the hydroxycloroquine and zinc thesis. https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDInv_zLVFTgXA8tW0Mf1iiuuM_&index=36&t=0s https://www.youtube.com/watch?v=U7F1cnWup9M&list=PLQ_IRFkDIn...
- Gibbon1 7y ago
  Part of the reason I'm suspicious of hydroxycloroquine and zinc is because for decades zinc and cloroquine have been fringe quack medicine staples for treating/preventing colds and flu.

egl2020 7y ago

You might have accumulated too much damage or other failure modes might have kicked in.

DiogenesKynikos 7y ago

From what I understand, in the late stages of the disease, it's not necessarily the virus that's killing the patient. Often, the virus has been cleared and it's the patient's own immune response that's doing the damage.

Mtinie 7y ago
This matches what I've read, too. It's less about the virus during the later stages and more about the infected person's immune system. If they've entered a state of amplified immune response, colloquially called a "cytokine storm," organs are damaged when their cells are mistakenly attacked. If you can moderate the immune system's reaction you can prevent significant damage. HCQ is useful for this type of immuno-suppression. Here's a pre-print of an article from a few years back which talks about HCQ and cytokine storms: Scott W. Canna, Edward M. Behrens. Making Sense of the Cytokine Storm: a conceptual framework for understanding, diagnosing and treating hemophagocytic syndromes. Pediatric Clinics of North America [Preprint]. April 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368378/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368378/ Published article link: https://dx.doi.org/10.1016%2Fj.pcl.2012.03.002 https://dx.doi.org/10.1016%2Fj.pcl.2012.03.002
- mundu_wa_hinya 7y ago
  The problem is that the immunosuppression by hcq takes a few weeks to kick in [1]. So it will not stop the Cytokine storm in time. tocilizumab seems to be a better option. 1. https://www.versusarthritis.org/about-arthritis/treatments/drugs/hydroxychloroquine/ https://www.versusarthritis.org/about-arthritis/treatments/d... 2. https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_InterimGuidelines_Treatment_ENG.pdf https://epidemio.wiv-isp.be/ID/Documents/Covid19/COVID-19_In...
  - mariodiana 7y ago
    My understanding is that tocilizumab is roughly 100 times as expensive as hydroxychloroquine and has intensive storage requirements. I don't see how the drug scales.

apendleton 7y ago

There's some evidence now that viral load peaks in the first week, and it's the second week that tends to be a problem for people with very serious cases. By the time many of these patients are hospitalized, their viral load is already going down on its own, and their serious complications are either due to immune overreaction (the so-called "cytokine storm"), or some sort of opportunistic co-infection like bacterial pneumonia. It's decently likely from what I've been reading that there might end up being effective pharmaceuticals for each stage, but that they'll be totally different from one another: maybe HCQ and antivirals like remdesivir or favipiravir early, and maybe immune-modulators like tocilizumab or even corticosteroids in this second phase. But again, the devil will be in the details, as it looks like HCQ doesn't work late, and steroids or other immune modulators might be actively harmful in that first stage when the virus is still surging. As for mechanism: nobody is really sure. HCQ does have some immune-modulating effects (that's what makes it useful for lupus), but there's also speculation that it might have some effect on the interaction between the ACE2 receptor and the coronavirus spike protein, and so somehow inhibit viral entry (see, e.g., https://www.nature.com/articles/s41421-020-0156-0 https://www.nature.com/articles/s41421-020-0156-0).