Does HCQ disable the Immune System's Viral Response?

[Aetherius Rimor]

Note: Relevant Academic Research links found towards the end of this post.

In July 2020 I decided to take a look at the Pharmacological Profile of Hydroxychloroquine. Upon seeing it was a TLR7 and TLR9 antagonist which are part of the Immune System's Viral Response, I immediately saw it as an incredibly dangerous "treatment" for COVID like many were touting; and based on my understanding it would make COVID far more lethal.

I wrote about this on my blog (pictures attached below) and tried to warn people but everyone was responded in one of the following ways:

1. If they didn't understand Pharmacology, they told me that my lack of formal education meant I had no idea what I'm talking about, berate me or accuse me of being part of some conspiracy theory .
   • I'm self-educated on this subject, thanks in large part to the people like y'all in forums like this !​
2. If they had studied medicine or pharmacology they typically suggested it needed to be formally studied in a clinical setting before such claims could be made or accepted; while refusing to say whether or not what I suggested was possible or likely based on its pharmacology.
   • They'd say something like "We don't know either way until there's more data." which unfortunately implies that it's impossible to predict or that all possibilities (beneficial/harmful/no effect) were equally possible.​
3. Or they'd straight up just ignore me completely for whatever reason.

This was extremely frustrating for me because I couldn't find anyone who could tell me how I was wrong or even consider what I was saying. I had also completely forgotten about this Forum and how much y'all helped me over the past decade as I was studying pharmacology, until today!

Y'all have successfully answered my questions every other time I had one no one else could answer so I trust y'all can with this one as well!

Here was my original blog post I wrote July 31st, 2020; updated with links to relevant academic research as I discovered them.

I desperately hoped I was wrong.​

The consequences of me being right were a lot of people dying if Hydroxychloroquine became popular as a treatment; a potentially massive tragedy due to an incredibly unbelievably unlucky coincidence... or pre-meditated mass murder if you're a conspiracy enthusiast .

Thankfully it disappeared like a passing fad shortly after I wrote this, so I forgot about it until today.

My Questions:

Do y'all have any thoughts on this? Also:

• If I'm wrong, please correct me by teaching me why and how I'm wwrong
• If I'm right, why didn't any other expert notice this or if they did, why didn't they say anything or get any publicity when they did?

Relevant Academic Research

• Pharmacological Profile
• TLR7 linked to COVID Lethality
• TLR9’s Role in Fighting COVID
• TLR7 and TLR9 Agonists as Potential COVID Treatment: Hydroxychloroquine did the opposite as an Antagonist

Mini Rant

This may be TLDR and is more me venting pent up emotions and frustration from 2020, so feel free to skip this part!

Not one person I showed this too had heard anyone else say what I was saying. Only one person said I was right but they were a patient using it for their Auto-Immune disease but they hadn't studied any of the science and they said no one listened to them either.

If her and I were correct, whatever prevented other experts from saying it potentially very dangerous is a problem that needs to be solved.

When one group of people says "it's a miracle cure" confidently and the other group is saying something that most people interpret as "we don't know if it is or not (no research has been done or shows)" in an unconfident, scolding or pleading tone; many people will trust the confidently told lie that gives them hope.

The only way to counter "miracle cure" claims from being believed or "worth giving it a try" is an equally strong opposing claim. One from an expert countering with "actually based on our understanding of the pharmacology and immunology; HCQ interferes with the immune system in ways that would make COVID far more deadly. Until there is research disproving this, all current research suggests it's deadly to treat COVID with HCQ."

Whether or not I'm correct about HCQ, if there is a law, policy or ethical standard that prevents experts from pointing out potential dangers like this for any reason; then those rules still need to be modified to allow for. I'd consider failing to warn people in this way when it's possible as negligence that results in preventable harm.

But what do I know?

I'm just an amateur hobbyist .

 

[Skorpio]

I would say it is likely that hcq does not have very much effect one way or another on covid.

The sources cited in drug bank saying hcq was an antagonist at tlrs (citations 4 and 11) do not convince me that this is a robust effect of hcq administration.

While tlr signaling is involved in productions of type 1 interferons (key to the antiviral response), one hallmark of covid is evasion of the interferon response through repression of transcription of interferon related genes. This allows covid to replicate to a high enough level to trigger innapropriate neutrophil mediated immune responses which are the driver of much of the lung pathology (hence why the standard of care for treatment switches from antivirals to anti-inflammatories as symptoms worsen; in fact you could make the argument that hcq actually helps with covid. I personally don't buy that argument either, if toll like receptor signaling modulation had a big effect one way or another you would see epidemilogical data on opioid users either being more or less susceptible, as opioid use suppresses the transcription of a handful of these receptors, including tlr7).

I guess the other aspect is that some of the clinical trials on hcq were performed adequately (so many garbage, under powered trials that wouldn't be able to discern even a penetrent effect tho, huge waste of time and money). None of these trials demonstrated a worsening of covid, just a lack of effect. That leads me to believe that gives effect on toll like receptor signaling is not clinically relevant to its in-efficacy towards covid.