COVID-19 Pathophys Discussion: Does HCQ/Avigan Actually Work?
I'm getting tired of all the circular arguments here regarding COVID-19 mostly by people with no medical background so I'm trying spur on a discussion behind the mechanism by which the virus infects cells and how it operates utilizing primary sources. We know the President has been touting HCQ therapy for a minute now, but the only literature I can find that promotes this therapy outside of anecdotal evidence and suspect blogs is from here:
Chinese caveats apply, but the gist of the study states that in conjunction to the already known mechanism of entry into cells via ACE2r respiratory epithelium, novel coronavirus may bind to membrane porphyrins leading to inhibition of heme metabolism w/ regards to RBCs. Drugs like HCQ and Avigan may reduce that binding all while preventing lysosomal release of proteases leading to decreased viral load.
My first problem with this is that it's a model that just seems to be trying to explain a correlation with regards to acute phase reactants (ESR, ferritin) and decreasing Hgb in a small select group of patients. From what I know there does not seem to be any significant drop in Hgb in pts as a whole and labs would easily pick up massive degradation of RBCs. On top of that, I don't see how the virus would even infect RBCs considering they lack all the essential organelles needed for proper replication. Coronavirus isn't a protozoa like Malaria, thus how would HCQ's lysosomal effects even be relevant in this case?
UPenn is currently conducting a trial to see if this makes sense. I will be curious to see if this angle has actual merit.
Circulation has recently published an article on how ACE2r's downstream effects might be the actual culprit in these cases:
https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047049
ACE2r converts Angiotensin I and II into Angiotensin 1,7 and 1,9 both of which are cardio-protective factors. Proteases like ADAM17 are upregulated when ACE2r is KO'd leading to expansion of pro-inflammatory markers such as TNF, IL4 and IFN. These things also lead to further coagulation issues (as reported from ICUs around the globe), vascular permeability problems (pulmonary edema, PNA) and myocardial issues (uncontrolled hypertension and MI).
We know pts with cardiac hx have higher expression of ACE2r and are thus at most risk and have the highest mortality associated with COVID-19. I'm more inclined to believe this angle rather than the hemoglobin one.
The curious case here is whether we continue drugs like ACEi/ARBs in these pts. Would depriving pts of substrates that can be converted into protective Angiotensin 1,7 and 1,9 be worthwhile? Or is that promoting a more harmful cascade in allowing for RAAS to function unmitigated?
NEJM has another good article regarding this:
https://www.nejm.org/doi/full/10.1056/NEJMsr2005760?query=featured_home
Thoughts?
Go to medcram.com
They have a series of videos that started on January 29th and did a new one everyday until the present. They go into great detail on the cellular mechanisms and studies of everything related to Covid-19. I especially liked the piece where he talks about immunity and the fact that you can't get it a second time.
Enjoy and stay healthy.
From a journal pre-proof:
"No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection"
https://www.sciencedirect.com/science/article/pii/S0399077X20300858?via%3Dihub
It seems to work much better as a prophylactic drug. Prevention not cure. We will all be taking it soon enough.
With its serious side effects? Not a chance in hell.
I thought I'd throw this out there: every Beaumont virus patient on a respirator that has been given HCQ goes into afib.
Every patient on a respirator goes into AFIB. Nice try.
Curious what some of the mgo medical professionals think about Dr. Cameron Kyle-Sidell’s theories?
Edit: replied to wrong comment.
He says this is a disease that doesn't make sense to us. That our usual treatments don't work. I disagree. This disease makes perfect sense to us. The epidemiologists knew what this was going to do and told governments how to contain, or at least slow it, but they didn't do those things. It isn't that our treatments don't work, it's that we don't have a treatment for it yet. The "usual treatments" currently being used are supportive care and waiting for the patient's immune system to get rid of the virus.
This guy seems to be an ER doc in New York, which means he's living a perpetual nightmare right now. But proclaiming that we don't know what this is and need to figure out new treatment is akin to running around, screaming, "Somebody do something!" There are already a lot of really smart people working the problem from a lot of different angles.
I'm not an expert here, nor did I sleep at a Holiday Inn Express last night.
Iran has had good success with Avigan, enough so that supplies are drying up if you aren't a high-ranking member of the regime. The country's main importer of the stuff is an IRGC company, and wonder of wonders the only way anyone else can get it is thru the black market. Funny how that happens.
Nothing I've seen suggests promoting it any more than Chinese herbal remedies or Vitamin C overdosing.
Edit: What I meant by this was that in times of panic everyone searches for a miracle. Based on what I've seen in the primary literature I'd be very surprised if this was it. I'm not promoting the other things.
I had to get my Roommate drunk to translate this kind of language to English. Fortunately it didn't take much.
A view from Pepe Escobar, celebrated journo for the Asia Times. The way this is blurring political lines is fascinating. Showed it to a friend who used to be the chief epedemiologist for the state of FL and he said there was little evidence it was useful.
https://asiatimes.com/2020/03/why-france-is-hiding-a-cheap-and-tested-v…
Meanwhile, there are a lot of approaches undergoing clinical trials, and a number of them may deserve more attention:
https://www.nakedcapitalism.com/2020/03/developing-a-vaccine-for-covid-…
Even though there is minimal evidence to justify widespread clinical use, I’d still want them if I was circling the drain. What do you have to lose at that point?
The downstream ACE mechanism is interesting. Thanks OP!
Dr. Anthony Cardillo (Los Angeles doctor) is saying that when paired with Zinc, Hydroxychloroquine has been very effective treating COVID-19, with very ill patients going basically symptom-free in 8-12 hours. But he is cautioning that HCQ be reserved for people who are very sick, otherwise we will blow through our supply for the patients who take it regularly for other disease processes.
So in other words... be responsible and take measured action. In this case, only if you're seriously ill with the virus. So we don't blow through it like we did toilet paper, meat products, canned goods, and other vital necessities that we ALL need to survive.
+1 Common sense.
This one goes to 11.
I can give you first hand information, that will like the science you are looking for yet relevant. I have had two family members on vents and it didn't look good. Both over 70 with issues. As a last resort both were put on HCQ + z pack and both were off a vent in 24 hours and out of the icu in 72 hours.
I have employees all over the country in hospitals in patient care/patient facing positions and many of the physicians are taking it as a prophylactic. This is primarily in areas like long island, washington, etc. They have actually offered our team to use it as well
Here is the text I received from a doctor taking it:
"Current protocol we are following as are my counterparts is same as for malaria prophylaxis, hydroxychloroquine 400mg po q wk on same day every week x 10 weeks. It's working, saving lives here."
Anecdotal evidence. It seems you are not a doctor, so your definition of "Didn't look good" may be different from that of health care workers. Patients everywhere are getting Plaquenil and azithromycin and anti-inflammatory monoclonal antibodies. None of it appears to be solving the problem. I'm glad your family members got better. Whether that was due to medications or because they were going to recover then anyway, nobody knows.
So just to clarify... what you're saying is that these don't work at all, and never will.
You can interpret the below how you’d like. This was the sequence...
This was after put on a ventilator:
“[relatives name here] is fighting for his life at this point but we’ve seen promise with a malaria drug you may have heard on the news. The evidence looks good but it is anecdotal and frankly we just don’t know enough except [insert bame] has no contraindications to the drug and we are at the ‘let’s try anything’ stage.”
After being taken off the ventilator:
”it appears the drug combo was the driving force that facilitated the turnaround.” I paraphrasing there was quite a bit of amazement.
when I asked why they are not giving it to everyone:
”there are people that should not take it we know a lot about the drug but it’s not clear why it’s working so well so we need to proceed with extreme caution until we learn more and only use in these cases”
as for the text that is from a physician at a medical center right in Long Island. They believe in it enough and have seen enough they are using it as a prophylactic. Many healthcare professionals are doing the same.
Personally, due to my job I likely will too and I’ve spoken with enough physicians who strongly believe in it I’m willing to take it as a prophylactic. Of course, I work in hospitals so I’m exposed and willing to take some risk if it helps protect me and my family.
i see where everyone is coming from but I’ve been to hospitals in WA, Long Island, Ohio and many others the past week and the consensus is this is working. Not a single facility. Literally not one, has said they have not seen overwhelming improvement from this drug in patients. I think the fact so many physicians are willing to take it as a prophylactic illustrates that point
nonsense---and source your claim of a consensus
C'mon, OP. You can do better than ripping a thread directly from RCMB.
/S
/Amazingly smart people here
My personal opinion, and this is just like my opinion man, is that if one cannot speak to the topic on this level then one shouldn't be touting.
Interesting question...and I like the research!
So let's ask another really good question... does the flu vaccine actually work?
I think the answer is firmly situated in grey area depending upon the individual taking the vaccine/medication and when they're taking it. Blocking the receptors that the virus attaches to is good in theory, depending on what stage they're in fighting it off. Similar to taking a few table spoons of iodine right before exposure to radiation to protect your thyroid. It's not a cure... but it may certain protect you from some of the proverbial fallout.
Anecdotal but I had two family members overseas test positive and treated successfully with hydrochloroquine. Both in upper 70s, one was a lifelong heavy smoker.
They have fully recovered.
Hmmmph...
It's anecdotal that cell phones and the radio/wi-fi waves that they use to communicate cause cancer, or harmful adverse effects to humans....
Yet, I don't leave my phone in my pocket next to my scrotum for obvious reasons. All I have to do is look over at my microwave to see what happens when I place meat inside there.
Hmmmm... is it really anecdotal? We haven't been able to effectively prove that lower frequency radio waves causes long term damage... the the anecdotal evidence sure as hell points to it.
I only put anecdotal because this isn't a lab setting with a double blind experiment.....I personally believe it helps as do other physicians but I get shouted down because I'm not a Dr. I have several in my family (including the two family members who tested positive) who agree with me but, again, not a clinical trial setting so it gets shouted down.
Here's another Dr. touting it: https://abc7news.com/coronavirus-drug-covid-19-malaria-hydroxychloroquine/6079864/
At some point, I hope all this anecdotal evidence gets loud enough to drown out all the naysayers.....just don't drink pool cleaner and you should be ok. And if you have heart conditons, it sounds like doxycycline would be a substitute for azythromycin.
It's great they recovered but the truth is it can't be considered THE cure because of all of the variables each patient presents, ergo, anecdotal. Also, many haven't responded to the CQ/HCQ so...anecdotal. We just don't know enough to definitively call something a cure. But be happy your family members were seemingly helped by these drugs and whatever else was involved in medicating. But know there will be people with science backgrounds calling a spade a spade; it isn't meant to downplay one's happiness/hope.
I'm honestly not trying to put it out as THE cure but as A potential treatment protocol. It's one thing to say this has promise and seems to be helpful and another to say it's the cure - I don't think we will ever see a CURE per se, not even a reliable vaccine, so it's important to find treatments that will alleviate symptoms.
Having said that.....I put it out there so people have something to discuss with their Dr. if they find themselves in this situation. It's just a "heads up", really. I'm also trying to be as positive as I can be and Fauci to be the absolute wrong person to have up there - he's clinically correct but not inspiring in any way and gives me the feeling he's loving the attention this has brought him. I don't get a good feeling from the guy at all.