I asked my Doctor friend about this. Among other things he studied at John Hopkins. Here is his feedback:
"I can point to about a million studies on HCQ or CQ which suggest both in vitro and in vivo it won't work, in addition to the studies in the clinic showing no benefit in any setting for COVID patients, including as a prophylactic. That substack article is far from rigorous and I wouldn't call what they did "research". They had a conclusion they wanted to reach and wanted to provide an illusion they were unbiased. I've come to learn that people are real bad at both research and critical thinking (including some scientists).
Let's start with this little relevant nugget. VERO cells, which the Virol J 2005 paper relies upon as a model for infection, are not lung epithelial cells - they are kidney-derived. Apparently substack authors neglected this little piece of relevant science - https://www.nature.com/articles/s41586-020-2575-3
Just from a drug efficacy standpoint, if you don't see in vitro effects at nanomolar concentrations, you're going to be hard-pressed to see any effect in vivo, much less in patients. Notably, even in VERO or other surrogate in vitro models demonstrating anti-entry or anti-viral replication effect upon CQ or HCQ treatment, the effects only appear at micromolar concentrations."
James, This Nature study was a very difficult study to read, and that accounts for the delay in our response. If we are to be self-governors - voters who own the democracy as the myth goes - then we must be able to understand the terms of our governance. Rule by experts is not our system of government. Thankfully so when politics is apt to narrow the ecosystem of approved experts.
We have already admitted, above, that we did not read this particular study before going to press. We also did not read countless others! The claim that we cannot comment until we've read everything anyone can possibly write on the subject would rule out your friend, as well - not to mention Tony Fauci!
But we're pretty sure now we weren't missing out on anything. Before this Nature study, there were at least 42 other in vitro studies concerning CQ and HCQ’s potential against coronavirus.
We were not agenda-driven in this effort, and we cannot afford to engage in a protracted debate. That said, we were motivated by your friend’s scientific input to report back on how HCQ performs in cells that express an enzyme that induces SARS-CoV-2 entry, despite HCQ treatment, and in contrast to SARS-CoV-1.
We didn't point to the 2005 Virology study as load bearing, let alone proof of concept for the HCQ cocktail treatment. We referenced in vivo studies to do that. Still, given that this 2005 in vitro study was concerned with SARS-CoV-1, we acknowledge a difference like this is significant.
“Cells that express both ACE2 and TMPRSS2 are present in multiple tissues including lung (alveolar and bronchial), buccal mucosa, nasal mucosa, ileum, colon, and myocardium epithelium. Recent studies of single-cell RNA sequencing further locate these highly susceptible cells in respiratory tree, cornea, esophagus, ileum, colon, gallbladder and common bile duct.” [https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009212]
Your friend likely has a point. TMPRSS2 expression might nullify those helpful roles. But we observed that one role (from the above linked instructional video) appears to stand—HCQ enables zinc to enter the cell, where zinc then independently works to inhibit viral replication.
In the interest of time, we haven’t explored how other zinc ionophores, like Quercetin, may in this respect have similar utility to HCQ. One may be more efficient or effective than the other. The HCQ reliance of many doctors who’ve treated COVID-19 patients suggests there’s a reason it’s a favored zinc ionophore in the context of an early treatment cocktail.
Also of note, “It has been indicated that azithromycin suppresses the pathways involved in the TMPRSS2 expression.”
“Another study [microbiologist Didier Roult’s second HCQ study - https://pubmed.ncbi.nlm.nih.gov/32387409/] examined the effect of azithromycin on patients with COVID-19 at the onset of early symptoms. This study included 1061 patients treated with azithromycin combined with hydroxychloroquine prior to the occurrence of COVID-19 complications demonstrated a low mortality rate and decent clinical outcome in patients.” [https://www.sciencedirect.com/science/article/pii/S0014299921003447]
A third study states: “We provide some evidence that azithromycin downregulates key pathways involving genes TMPRSS2 and TMPRSS11D, which code for two serine proteases required by SARS-CoV-2 for its activation and cell-to-cell transmission, respectively.” [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605155/]
We noted in the piece (above) that, “HCQ works as part of a 'team,' much like how AIDS was fought 25 years ago.” <<<This is crucial.
This statement is based on the experience of doctors who have been remarkably successful with the early treatment cocktail. Zinc and azithromycin play on this team. [https://swprs.org/on-the-treatment-of-covid-19/] In our research we came across many studies that no doubt helped inform these doctors, and also many studies that conclude HCQ is likely ineffective for COVID-19 treatment. With many of those latter studies, we observed common threads in their methodology that caused them to fall outside of the HCQ strategy favored by these doctors who’ve found success.
We appreciate the chance to address your critical feedback. It gave us an additional degree of peace about our work. And that work was NOT to prove HCQ works; that's not for us to decide. It was that the coverage of this treatment was unbalanced, and that, dangerously, the normal methods of both science and journalism, along with the traditional methods of medical practice, have been abandoned in this case.
Thank you for the detailed reply. I too try to get into the weeds, and around the unbalance I see. It becomes hard with knowing who the real experts are, and I would like to see better journalism standards (similar issues exist with the lab leak hypothesis).
You may not want to keep this up, but here's the response:
"This mechanism of action - "HCQ enables zinc to enter the cell, where zinc then independently works to inhibit viral replication" is likely not how HCQ would actually work, in cases where it does show effect. Nevan Krogan's manuscript - https://www.nature.com/articles/s41586-020-2286-9 nominates the Sigma-1 receptor as a target of SARS-CoV-2, which HCQ/CQ can interfere with.
A zinc ionophore mechanism of action doesn't make sense from a simple stoichiometry/concentration standpoint. If HCQ is acting as a zinc ionophore, and that is the requirement for anti-viral activity, then you'd need ridiculously high in vivo concentrations of HCQ to observe much effect as there would be no specificity. Furthermore, most metals are not "free", but rather bound to molecules like albumin or transferrin (iron) and 'handed off to' or 'scavenged by' other proteins inside the cell (such as metallothioneins)."
Two things. 1) We take this comment seriously, and are grateful for the insight. We may well have further response. Please stay tuned (check back) for that. 2) As we stated in the article, we ran out of bandwidth, and chose to share what we learned. We're looking at this study now.
What about it? When there are hundreds of real world studies, that is where to look. And why would we care all that much whether chloroquine was effective in cancerous lung cells, anyhow? What does that have to do with anything?
I do understand your dilemma's in this article. I would advise to start by finding good experts, then see what they say, and dig into that. If you process is "let me find the information myself" good luck! Unless you yourself are an expert, it will be very difficult, and even then there will be challenges.
I just can’t help feeling flattened on a daily basis anymore. I don’t even watch cable news anymore. An Xmas gift to myself!! Social Media is like navigating the aftermath of a nuclear bomb drop. Glad someone is attempting to sort through the debris... 😔 Note: There’s a error on the date in paragraph about Milan (July/2021) It’s only May! 😉 Keeping you on your toes!!!
The French microbiologist is not a medical doctor. He had a 91.7% success rate for a disease that some people say has a 99.8% survival rate, do try and get your story straight. In reality it has a 97% survivability, so a 91.7% rate is worse than doing nothing.
The French microbiologist has written treatments for a dozen diseases, stopped an epidemic in its tracks, discovered 500 of around 2500 human borne microbes, and is most published in infectious diseases.
The attempt to minimize and belittle him is pathetic and disturbing.
I believed the HCQ was ineffective narrative. Hated masking up but did it because I could see the logic for doing so in close contact with strangers. And I’m fully vaccinated. So apparently I can let the mask slide as if today. I get tired of the labeling and nonstop drama. But I apparently qualify as a Communist sheep about to leap from the proverbial cliff in some peoples eyes even though politically I am center right. So that probably qualifies me as a RINO? And now I’ve forgotten why I replied to your comment because I also qualify as OLD!!! Oh yeah!!! Nothing is worse than doing nothing!!! 🤗
Long QT syndrome is a cardiac conduction abnormality not a pulmonary condition.
Bill, thanks for pointing this out! We've corrected that in the article.
My pleasure, I didnt go to evil paramedic school to not be helpful 🤣
I asked my Doctor friend about this. Among other things he studied at John Hopkins. Here is his feedback:
"I can point to about a million studies on HCQ or CQ which suggest both in vitro and in vivo it won't work, in addition to the studies in the clinic showing no benefit in any setting for COVID patients, including as a prophylactic. That substack article is far from rigorous and I wouldn't call what they did "research". They had a conclusion they wanted to reach and wanted to provide an illusion they were unbiased. I've come to learn that people are real bad at both research and critical thinking (including some scientists).
Let's start with this little relevant nugget. VERO cells, which the Virol J 2005 paper relies upon as a model for infection, are not lung epithelial cells - they are kidney-derived. Apparently substack authors neglected this little piece of relevant science - https://www.nature.com/articles/s41586-020-2575-3
Just from a drug efficacy standpoint, if you don't see in vitro effects at nanomolar concentrations, you're going to be hard-pressed to see any effect in vivo, much less in patients. Notably, even in VERO or other surrogate in vitro models demonstrating anti-entry or anti-viral replication effect upon CQ or HCQ treatment, the effects only appear at micromolar concentrations."
James, This Nature study was a very difficult study to read, and that accounts for the delay in our response. If we are to be self-governors - voters who own the democracy as the myth goes - then we must be able to understand the terms of our governance. Rule by experts is not our system of government. Thankfully so when politics is apt to narrow the ecosystem of approved experts.
We have already admitted, above, that we did not read this particular study before going to press. We also did not read countless others! The claim that we cannot comment until we've read everything anyone can possibly write on the subject would rule out your friend, as well - not to mention Tony Fauci!
But we're pretty sure now we weren't missing out on anything. Before this Nature study, there were at least 42 other in vitro studies concerning CQ and HCQ’s potential against coronavirus.
We were not agenda-driven in this effort, and we cannot afford to engage in a protracted debate. That said, we were motivated by your friend’s scientific input to report back on how HCQ performs in cells that express an enzyme that induces SARS-CoV-2 entry, despite HCQ treatment, and in contrast to SARS-CoV-1.
We didn't point to the 2005 Virology study as load bearing, let alone proof of concept for the HCQ cocktail treatment. We referenced in vivo studies to do that. Still, given that this 2005 in vitro study was concerned with SARS-CoV-1, we acknowledge a difference like this is significant.
Here's the summary of our response: “The SARS-CoV-2 entry process is more dependent than that of SARS-CoV-1 on TMPRSS2 expression.” [https://www.biorxiv.org/content/10.1101/2020.07.22.216150v1.full.pdf]
“Cells that express both ACE2 and TMPRSS2 are present in multiple tissues including lung (alveolar and bronchial), buccal mucosa, nasal mucosa, ileum, colon, and myocardium epithelium. Recent studies of single-cell RNA sequencing further locate these highly susceptible cells in respiratory tree, cornea, esophagus, ileum, colon, gallbladder and common bile duct.” [https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009212]
An informative 10 minute video "How hydroxychloroquine works at the cellular level" [https://www.palmerfoundation.com.au/how-hydroxychloroquine-works-at-the-cellular-level/] gives a little bit deeper mechanical understanding of how HCQ plays several helpful roles in SARS-CoV-2 treatment.
Your friend likely has a point. TMPRSS2 expression might nullify those helpful roles. But we observed that one role (from the above linked instructional video) appears to stand—HCQ enables zinc to enter the cell, where zinc then independently works to inhibit viral replication.
In the interest of time, we haven’t explored how other zinc ionophores, like Quercetin, may in this respect have similar utility to HCQ. One may be more efficient or effective than the other. The HCQ reliance of many doctors who’ve treated COVID-19 patients suggests there’s a reason it’s a favored zinc ionophore in the context of an early treatment cocktail.
Also of note, “It has been indicated that azithromycin suppresses the pathways involved in the TMPRSS2 expression.”
“Another study [microbiologist Didier Roult’s second HCQ study - https://pubmed.ncbi.nlm.nih.gov/32387409/] examined the effect of azithromycin on patients with COVID-19 at the onset of early symptoms. This study included 1061 patients treated with azithromycin combined with hydroxychloroquine prior to the occurrence of COVID-19 complications demonstrated a low mortality rate and decent clinical outcome in patients.” [https://www.sciencedirect.com/science/article/pii/S0014299921003447]
A third study states: “We provide some evidence that azithromycin downregulates key pathways involving genes TMPRSS2 and TMPRSS11D, which code for two serine proteases required by SARS-CoV-2 for its activation and cell-to-cell transmission, respectively.” [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605155/]
We noted in the piece (above) that, “HCQ works as part of a 'team,' much like how AIDS was fought 25 years ago.” <<<This is crucial.
This statement is based on the experience of doctors who have been remarkably successful with the early treatment cocktail. Zinc and azithromycin play on this team. [https://swprs.org/on-the-treatment-of-covid-19/] In our research we came across many studies that no doubt helped inform these doctors, and also many studies that conclude HCQ is likely ineffective for COVID-19 treatment. With many of those latter studies, we observed common threads in their methodology that caused them to fall outside of the HCQ strategy favored by these doctors who’ve found success.
We appreciate the chance to address your critical feedback. It gave us an additional degree of peace about our work. And that work was NOT to prove HCQ works; that's not for us to decide. It was that the coverage of this treatment was unbalanced, and that, dangerously, the normal methods of both science and journalism, along with the traditional methods of medical practice, have been abandoned in this case.
Thank you for the detailed reply. I too try to get into the weeds, and around the unbalance I see. It becomes hard with knowing who the real experts are, and I would like to see better journalism standards (similar issues exist with the lab leak hypothesis).
FYI - I found this article through The Advocates.
You may not want to keep this up, but here's the response:
"This mechanism of action - "HCQ enables zinc to enter the cell, where zinc then independently works to inhibit viral replication" is likely not how HCQ would actually work, in cases where it does show effect. Nevan Krogan's manuscript - https://www.nature.com/articles/s41586-020-2286-9 nominates the Sigma-1 receptor as a target of SARS-CoV-2, which HCQ/CQ can interfere with.
A zinc ionophore mechanism of action doesn't make sense from a simple stoichiometry/concentration standpoint. If HCQ is acting as a zinc ionophore, and that is the requirement for anti-viral activity, then you'd need ridiculously high in vivo concentrations of HCQ to observe much effect as there would be no specificity. Furthermore, most metals are not "free", but rather bound to molecules like albumin or transferrin (iron) and 'handed off to' or 'scavenged by' other proteins inside the cell (such as metallothioneins)."
Two things. 1) We take this comment seriously, and are grateful for the insight. We may well have further response. Please stay tuned (check back) for that. 2) As we stated in the article, we ran out of bandwidth, and chose to share what we learned. We're looking at this study now.
Thanks!
The Johns Hopkins doctor should just focus on the early treatment (optimal) studied.
Credentials aren't everything.
https://roundingtheearth.substack.com/p/the-chloroquine-wars-part-xx
What about this Nature link?
What about it? When there are hundreds of real world studies, that is where to look. And why would we care all that much whether chloroquine was effective in cancerous lung cells, anyhow? What does that have to do with anything?
The nature link is not about Cancer though? It is "Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2"
.
I'll read and review your new link. Thanks!
I do understand your dilemma's in this article. I would advise to start by finding good experts, then see what they say, and dig into that. If you process is "let me find the information myself" good luck! Unless you yourself are an expert, it will be very difficult, and even then there will be challenges.
Another article that support HCQ as an alternative treatment (with Zn, plus).. https://assets.website-files.com/606d3a50c62e44338008303d/6076fe1361cd5d631ecb0a32_White-Paper-on-HCQ-2020.2.pdf
Dr. Gold explain standard of care & how it was violated during the "pandemic".
I just can’t help feeling flattened on a daily basis anymore. I don’t even watch cable news anymore. An Xmas gift to myself!! Social Media is like navigating the aftermath of a nuclear bomb drop. Glad someone is attempting to sort through the debris... 😔 Note: There’s a error on the date in paragraph about Milan (July/2021) It’s only May! 😉 Keeping you on your toes!!!
Marcia, thanks for catching that and letting us know! The date has been fixed.
The French microbiologist is not a medical doctor. He had a 91.7% success rate for a disease that some people say has a 99.8% survival rate, do try and get your story straight. In reality it has a 97% survivability, so a 91.7% rate is worse than doing nothing.
The French microbiologist has written treatments for a dozen diseases, stopped an epidemic in its tracks, discovered 500 of around 2500 human borne microbes, and is most published in infectious diseases.
The attempt to minimize and belittle him is pathetic and disturbing.
I believed the HCQ was ineffective narrative. Hated masking up but did it because I could see the logic for doing so in close contact with strangers. And I’m fully vaccinated. So apparently I can let the mask slide as if today. I get tired of the labeling and nonstop drama. But I apparently qualify as a Communist sheep about to leap from the proverbial cliff in some peoples eyes even though politically I am center right. So that probably qualifies me as a RINO? And now I’ve forgotten why I replied to your comment because I also qualify as OLD!!! Oh yeah!!! Nothing is worse than doing nothing!!! 🤗