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?
Yes.
As far as the East is from the West.
You're like the 5th best quad on campus. (West, Law, South, North, East)
Jealousy will get you a red ass, but nothing else.
Where does Couzens fit in?
Met 80% of my present-day friends (and current wife) in Couzens. Rights high as hell for me.
Couzens is pathetic, terrible dorm, and everybody knows it. It's a fake dorm really, and sends us all the worst people.
West Quad is tremendous, everyone is saying it. All the best people, biggest meals, tremendous place really. You know it, I know it, all the smartest people are saying it. There's not another dorm like it in the world - biggest, best, tremendous - a perfect dorm really.
and dominated the South Quad snowball fight when I lived there. . . .
Likewise for me....which is surprising given all the athletes that lived there at the time.
I think my daughter should be the arbiter in this dispute. Freshman year was in West (East was being remodeled), sophomore year in East. I definitely side with East ... Hinsdale, Tyler and RC Singers rule!!
As a graduate of the RC and founder of the co-oop wing of EQ (is it still there?) I salute you.
Actually, I got the hell out in the middle of my second year--that place was a sexual zoo.
I like the picture in the NEJM. It is about the only thing that I understand in the article, I'm afraid.
What is the name of the grill in East quad that accepts the m card. That place made a mean hot ham and cheese when redrum was poor
Half Ass Inn (Half Way Inn)- open late night- live music on the weekends. Alas it went away when remodeled. I preferred the grilled veggies on grilled bagel with melted swiss.
I spent many a night on the pinball machines in the Half Way Inn in the 70s. Also in the billiards room, playing pool. I am surprised sometimes that I actually graduated, considering the amount of time I screwed off instead of studying. B-school to boot!
Double post.
Username checks out
MGoBlog - come for Michigan sports, stay for the Michigan Medicine Biochemistry
My amateur hope is that the antibodies used by SARS-CoV recoveries can be used to fight this/CoV-2. It seems all of these Corona viridae all contain conserved binding sites although the Cov-2 is not yet reacting as well with the antibodies. But hopefully continued efforts find a way to make this concept work and we can eventually disarm the virus. Another hope is a drug that has already been utilized in Washington to good effect, that inhibits transcription by disarming the RDRP.
My understanding is Coronavirus' primary entry is via receptor (ACE2)-induced fusion and its large spike attaching to it, but Chloroquine's mechanism of action revolves around the endocytosis of the virus, the less utilized entry method. That may help a small bit but not enough and isn't stopping the primary entry.
Edit...here we go! From 2 weeks ago
"The available data are thin. The drugs work by decreasing the acidity in endosomes, compartments inside cells that they use to ingest outside material and that some viruses can coopt to enter a cell. But the main entryway for SARS-CoV-2 is a different one, using its so-called spike protein to attach to a receptor on the surface of human cells. Studies in cell culture have suggested chloroquines have some activity against SARS-CoV-2, but the doses needed are usually high—and could cause serious toxicities"
I’ve read that one theory why children are responding better to infection with Cov-2 Is that they’re more used to fighting coronaviruses, as they cause several versions of the common cold, and are typically passed amongst children at much greater frequency than adults. Might lend some credence to what you say above, but who knows. I’m a chemist, damnit, not a virologist!
I’m a chemist too but I still cite my sources. ;-)
I don't think anyone on this sub understood about 90% of this post
I think the biggest thing is that Trump should not be publicly pushing a drug cocktail that has not undergone extensive testing and has shown to have serious side effects. At least 1 person has already died from taking his non medical opinion to heart
To your first point, to me it was quite obvious that was the point!
We're getting more clinical data on hydroxychloroquine (both from China and France) and it is showing some promise. Still, it's a prescription drug - people shouldn't be trying to self-medicate with it.
Exactly. If it shows to have promise after extensive testing, then amazing. But peddling that it has promise without that being true is a dangerous medical precedent
The guy who died drank fish tank cleaner. Do you really think Trump is to blame for that? Also, it has come to light that the wife is a Democrat activist and has had a difficult marriage, including charges of domestic violence directed against the husband. It may turn out to be a homicide where she saw a chance to get rid of her husband and blame Trump, a win-win from her perspective.
Take off your tin foil hat
And yes, I do think Trump is partially to blame
I've watched enough forensic files to know spouses can come up with creative ways of killing their SO when there's enough motivation to be rid of them
people are numb to the tin foil hat comments. I think lots of people are in denial about how many f*#ked up things have been happening over the last 3 years and cant get their heads around how much lying is going around through the media, justice system, law enforcement, science, banking etc.
The conspiracies are only just beginning to come to light, that's a promise. Buckle up dorothy, you're not in Kansas anymore.
The funny thing about you tin foilers is that you only believe and respect the conspiracies that match your baseline political leanings. What about the crazy liberals who think that Trump is only pushing this drug because he has some secret stock in Novartis and is desperate to make money because he’s terrified that his fake empire is gonna come crashing down after his term is over?
Does that get your seal of conspiracy approval?
Trump is here to lead the nation as an organization, not as a parent or role model; that's what most of you don't get. As an adult... if you need someone in political office to tell you when to wash your hands and how to be healthy, and other basic life skills... then the only entity that has failed is our public education system. Stop blaming Trump for the decisions YOU make. As an independent this is the problem that I have with Liberalism, we legislate and make rules for the lowest common denominator... you can't do that, you have to educate people and let the chips fall where they may.
Hell, New Orleans governor was blaming Trump because she wasn't told specifically to cancel Mardi Gras....absolutely ridiculous! This is the problem with local politicians and people in general these days, they all want to blame someone else and 'play stupid' after the fact. Stop it... take responsibility for your life, do your part.. isolate, wash your hands, be smart, be the solution!
I don't know why you're being downvoted.....nobody wants to take personal responsibility anymore.
Hey bud! Welcome to MGoBlog! You must be new here!!
This place is crawling with political spin. Especially from the Libs. They all have the TDS (Trump Derangement Syndrome). They think we’d be better off with Breadline Bernie or sleepy Joe... good thing we won’t find out if that’s true!! Trump in 2020 by a LANDSLIDE.
You spend more time with pithy nicknames than I spend insulting Conservatives. Try spending your time on considerate ideas rather than insults—or just being a sycophant to poor decision maker.
My time is spent at work. Battling corona virus. In the ICU. Thanks for the advice tho.
If the democrats had a decent candidate, you’d have a shot at winning.
But you don’t.
You are only left with the liberal owned media to come up with the next anti-Trump campaign. All of which have been lies (but it must be true if it’s on CNN and Brian Stetler and jim Acosta reported it, right???).
America is sick and tired of their spin.
Also, you Can always tell a Democrat by the big words they like to use (sycophant, xenophobe, etc.). Or because anytime there is a valid argument from the right you all yell “racist”.
You need to spend more time working on the solution than blaming politicians... no matter who/which party they belong to.
Like I said. I am one of the Americans working right now. I work in a hospital. In an ICU. I’m a nurse. So to tell me that I need to do more...well, great! What more should I do for you? Want me to come help you with yard work? When I get a day off I’d be glad to! Just give me another way to help society through this and I’ll be glad to help in any way that I can.
Sorry I’m Just really sick of the Liberal/left owned media...and the dems BLAMING THIS VIRUS ON TRUMP. Trying their hardest to put any sort of anti-trump spin on it to help their cause. It’s a fucking joke that people buy this.
It’s us against the virus people.
On a side note, we are prescribing Plaquenil and Zithromax to patients. Also zinc supplements. A few other anti-viral HIV drugs as well.
My take on this whole virus is....if you’re lucky and your immune system responds Favorably to it, you’ll be fine whether you take the aforementioned drugs or not.
Some people however seem to have an over-reaction to the virus in their lungs. These are the people that tend to not do well. Even if they rec’d the drugs. The part we are having a hard time understanding right now is why some people react the way they do. And others don’t. For the ones that don’t respond well...it’s an agonizing experience in the ICU. That probably more than 50% of the time does not end well.
Spend more time tending to patients then arguing pointlessly on Internet?
It took less than three minutes cuz.
Even us healthcare workers need to vent.
Now... shut CNN/msdnc off.
Go wash your hands.
Don’t touch your face.
Yes. His answer to anything remotely requiring medical knowledge should be "I'll defer to Dr. Fauci for that answer."
He. Can't. Let. It. Go.
I’d be 100% ok with this. Trump has a HUGE ego and his mouth often does him no favors. I’m a firm believer that humility opens a lot more doors than arrogance.
I voted for him for his drain the swamp mentality. I voted for him because he loves the USA. He loves our veterans. And because we needed a business man to run the country.
Obama was perfectly content with America getting bent over and being everyone’s bitch. Yea...he was an eloquent speaker, a smooth talker, and could read off a teleprompter like no other....but he did NOTHING for our country as far as I’m concerned.
Donald trump had the economy roaring...and if it’s going to happen again, it will take trump as president.
Elect Bernie sanders and we will tumble into a decade long recession if not worse.
Elect Joe Biden and his hand chosen VP will be running our country within a month.
The left is a COMPLETE FUCKING CLOWN SHOW, and I think even their own people are beginning to realize it. Theirs no moderates left to vote for there. But they own the media...so they have a punchers chance.
*There’s
The real question is how much stock in the drug company that makes it has trump and his criminal family bought up in the past few weeks. Dr. Fauci continues to pull back on this "miracle drug" (as well he should) while Trump can't keep his stupid mouth shut about it.
Don’t cancer doctors do this ALL the time with low probability last ditch drugs? The false hope vs “real” hope is stupid, as we really don’t have time. It’s going to be a real time test whether we like it or not.
I think he is referring to the people in Arizona who took the phosphate salt which is available as a fish tank cleaner.
The person that died used fish tank cleaner NOT the actual drug.
Edit: Mgotri is absolutely correct. Ingesting chemicals used to clean fish tanks is a huge leap from what Trump was suggesting.
Look, Trump May have a mouth that he needs to shut more often, but the person didn’t die from his advice. They ate fucking fish bowl cleaner. That’s not on him. If someone were to tell me that zinc supplements will help with my symptoms and I die because I ate three dollars worth of quarters, that’s on me.
Yes. That is on them for doing something obviously stupid.
However it is still irresponsible for anyone to promote an investigational drug. There are strict restrictions about how pharma companies can talk about there pre-approval drugs and the one of reasons you don’t hear about the next great biotech company on Shark Tank. I have mixed feelings about it being national news reporting on these trials.
the reason for this is that this type of reporting gives false hope to desperate and uninformed people. Those people will then take desperate measures to get what they think will help them, but is really only being investigated.
It does not matter which president does it. It is alway irresponsible.
My MIL is convinced that this drug will save her if she gets the rona.
From a Michigan Medicine piece on anti-malarials, i.e., hydroxychloroquine. TL:DR summation - no longer being used routinely at Michigan.
Should people with COVID-19 take chloroquine or hydroxychloroquine? Do you prescribe them to your patients with COVID-19?
Michigan Medicine just changed its guidelines on prescribing these drugs. There’s a lot of excitement about whether these already existing options for malaria could be useful in COVID-19, but so far that excitement hasn’t materialized in patient care data.
“Our infectious disease division and our antimicrobial pharmacists have reviewed all the available data and we found no convincing evidence that these drugs were effective in treating people with COVID-19,” Kaul says.
That’s consistent with what’s been observed firsthand in Michigan Medicine’s hospitals.
“We haven’t seen any clear evidence of benefit so we aren’t going to use hydroxychloroquine routinely anymore,” Chopra says. “We were initially recommending it to both inpatients and outpatients, but we’re no longer doing that routinely. That’s based upon the fact that we’ve been prescribing hydroxychloroquine for a few weeks, did not see therapeutic benefit, but did see adverse effects.”
Those side effects Chopra has seen in his patients include liver function toxicity, nausea and vomiting.
Moving forward, Chopra and Kaul say the strategy is to individualize these decisions for each patient, considering risks and benefits based on that person’s health history and symptoms.
Chopra notes that use of chloroquine or hydroxychloroquine could also exclude a patient from being allowed to join other COVID-19-related clinical trials, so it’s important to consider all of these factors before prescribing the drug.