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Posted (edited)

I thought it would be helpful to have a thread specifically for medical discussion and developments - vaccines, treatments, clinical trials, personal medical questions for surly docs, etc.

I'll start with a topic that's been of interest to me. My only medical condition is an autoimmune disease that is treated with hydroxychloroquine with excellent control. I've considered the potential impact of the condition itself vs. the treatment with regards to my immune system. Fortunately for me, there has been some literature published about chloroquine and hydroxychloroquine as potential treatments for COVID.

  Quote
In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

https://www.ncbi.nlm.nih.gov/pubmed/32150618

Abstract
BACKGROUND:

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection.

METHODS:
The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug's safety profile.

RESULTS:
Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance.

CONCLUSIONS:
Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

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Edited by wild_turkey
Posted (edited)

My 2 separate quotes were getting combined for some reason. Here's the second one I wanted to list:

  Quote

Chloroquine and hydroxychloroquine as available weapons to fight COVID-19.

https://www.sciencedirect.com/science/article/pii/S0924857920300820?via%3Dihub

Regarding viruses, for reasons probably partly identical involving alkalinisation by chloroquine of the phagolysosome, several studies have shown the effectiveness of this molecule, including against coronaviruses among which is the severe acute respiratory syndrome (SARS)-associated coronavirus [1,12,13] (Table 1). We previously emphasised interest in chloroquine for the treatment of viral infections in this journal [1], predicting its use in viral infections lacking drugs. Following the discovery in China of the in vitro activity of chloroquine against SARS-CoV-2, discovered during culture tests on Vero E6 cells with 50% and 90% effective concentrations (EC50 and EC90 values) of 1.13 μM and 6.90 μM, respectively (antiviral activity being observed when addition of this drug was carried out before or after viral infection of the cells) [3], we awaited with great interest the clinical data [14]. The subsequent in vivo data were communicated following the first results of clinical trials by Chinese teams [4] and also aroused great enthusiasm among us. They showed that chloroquine could reduce the length of hospital stay and improve the evolution of COVID-19 pneumonia [4,6], leading to recommend the administration of 500 mg of chloroquine twice a day in patients with mild, moderate and severe forms of COVID-19 pneumonia. At such a dosage, a therapeutic concentration of chloroquine might be reached. With our experience on 2000 dosages of hydroxychloroquine during the past 5 years in patients with long-term treatment (>1 year), we know that with a dosage of 600 mg/day we reach a concentration of 1 μg/mL [15]. The optimal dosage for SARS-CoV-2 is an issue that will need to be assessed in the coming days. For us, the activity of hydroxychloroquine on viruses is probably the same as that of chloroquine since the mechanism of action of these two molecules is identical, and we are used to prescribe for long periods hydroxychloroquine, which would be therefore our first choice in the treatment of SARS-CoV-2. For optimal treatment, it may be necessary to administer a loading dose followed by a maintenance dose.

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Edited by wild_turkey
Posted

I have been looking at the Plaquenil/Zinc data on the original SARS virus and then also recovered Covid patient antibodies from their serum.  If I get really sick for some reason then I'm begging for these two treatments.

 

Posted
  On 3/14/2020 at 7:36 PM, Parliament said:

My wife's sister sells essential oils on Facebook, and she says they help. I'll get he your contact info.

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I’ve been huffing one of those Gwyneth Paltrow poon candles for the last week and, as far as I can tell, I haven’t died of coronavirusitis yet.  

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Posted (edited)

Everyone should take zinc supplements while this is going on. Little downside. Has demonstrated anti-viral activity. 

Edited by GRHorn
Posted

So I take a daily vitamin that has zinc in it, wouldn’t that sufficient? I remember talking to a doctor a few years back and he made a remark that Americans have the most vitamin rich piss in the world due to lack of absorption. 

Posted (edited)

There were several different news outlets based in the Philippines that reported yesterday on a medication that allegedly is showing promise in helping to overcome severe Sars-Cov-2 infection.  CNNPhilippines article here.

The drug is called Cycloferon.  Abstract from a 2015 Russian article on it:

Abstract

Results of the use of cycloferon, a low molecular weight inducer of interferon production, for the treatment and prevention of influenza and acute respiratory viral infections (ARVI) in adults and children are presented It was shown to reduce symptoms of these diseases and their duration, correct disbalanced activity of the immune system, prevent complications, decrease the frequency of influenza and ARVI. The effectiveness of cycloferon did not depend on etiology of the disease.

 

---> "disbalanced activity of the immune system" sounds like "cytokine storm" we've been hearing about in the severe Covid cases.  We know about 80% of cases of this are mild and then there's a minority, albeit very significant in numbers, that have a very complicated course that can be fatal, or if not fatal result in scarring of the lungs (fibrosis) which is a bodily response.  If Cycloferon targets neutralizing those cases that would otherwise run amok, that would make sense as an intervention.

If there's some validity to this, any validity at all, it would certainly be welcome news.

Edited by triplehorn
Posted

Interesting podcast here with Italian Er doc interview. Fascinating how they’ve had to change their processes, but in the end, they’re getting it done. 

 

Posted

My wife is in biotech, and basically says we're fucked.

In my best dumbass, Neanderthal attempt at translation: it's a complex test with a lot of moving parts, delicate collection, and strict temperature requirements that requires a high level of technical proficiency. The small labs are inadequate to keep up with the demand. Currently there are 78 labs only processing 1000 tests a day. Even then, they need enough positive and negative tests to create a solid "baseline" to verify positive tests. Larger labs are working to create that validation to share, but it may take 6-12 weeks. Many labs are saying "F it" and developing their own tests.

Posted

Question about tests for you medical guys.

Is this test similar to others where they test for the presence of antibodies?

Specifically, if that is the case, if someone is “asymptotic”, how do we know that they are actually currently “infected” or is all we really know Is that they were exposed to the virus previously and now they are immune for lack of a better term?
 

In other words, what is the difference between being asymptomatic and being immune?

 

Posted
  On 3/15/2020 at 3:00 AM, crimsonlonghorn said:

Question about tests for you medical guys.

Is this test similar to others where they test for the presence of antibodies?

Specifically, if that is the case, if someone is “asymptotic”, how do we know that they are actually currently “infected” or is all we really know Is that they were exposed to the virus previously and now they are immune for lack of a better term?
 

In other words, what is the difference between being asymptomatic and being immune?

 

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Symptoms are created by the body as a product of response to an infection.  Different people's bodies can produce different symptoms to the same bug, which can be pretty specific or range greatly in some cases like we're seeing with Covid, and can include minimal or no perceivable symptoms of infection.  However an actual test can prove the bug is present using a microscope, or in the case of Covid, spotting its genetic material with a test from a swab of your nose, throat, sputum, or as it turns out stool.

Being immune is when the infection is over, symptoms are gone, and the immune system retains a lasting memory of that initial infection.  You won't visibly find the bug or readily find its genetic material in a sample.  

You can test blood at any time and look for the presence or absence of immune memory in the form of antibodies which can indicate if you have been exposed to a bug or not, even if you have no recollection of ever having had symptoms.  

 

Posted

Another write-up: Of chloroquine and COVID-19

Basically it says we need to see the Chinese data to substantiate their reports.  It should be noted however that SoKo and Italy both have also employed chloroquine in their management, so the power of clinical observation is motivating their treatment right now.

Two days ago I started taking a prescription of chloroquine for off-label use of a presumed active Covid infection from an understanding physician.  I don't have signs of progression to pneumonia so far - the biggest fear - and I feel better today than I did the last 3 days when it was mildly harder to breathe.  The risks of lung involvement seem a lot worse than any side effects of of chloroquine.  No idea if its related to any changes in how I feel but grateful its not worse right now

 

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Posted (edited)

I post this relating to the tinyurl links in the middle.  Good quick reads in each one.  The larger thread that Sinclair made is also interesting.  Sinclair is probably best known for his work on the molecular biology of aging.

From that 'therapies' one: 

"Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir / ritonavir, lopinavir / ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. "

 

Edited by triplehorn
Posted
  On 3/15/2020 at 4:38 AM, triplehorn said:

Two days ago I started taking a prescription of chloroquine for off-label use of a presumed active Covid infection from an understanding physician.  I don't have signs of progression to pneumonia so far - the biggest fear - and I feel better today than I did the last 3 days when it was mildly harder to breathe.  The risks of lung involvement seem a lot worse than any side effects of of chloroquine.  No idea if its related to any changes in how I feel but grateful its not worse right now

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Obviously you are doing this under the direction of a physician, but I want to point out for everyone else that chloroquine does have side effects of cardiomyopathy and retinal toxicity. It probably goes without saying, but no one should attempt to obtain these medicines or any other potential COVID-19 treatments except through their physician. The benefit here is still unclear with limited published data and a lot left to learn.

  • Like 1
Posted

It will be very interesting to see in a year or so how many people actually have +IgG for Covid-19. I guess that is when we’ll have the true denominator here. 

Posted
  On 3/15/2020 at 7:53 PM, wild_turkey said:

Obviously you are doing this under the direction of a physician, but I want to point out for everyone else that chloroquine does have side effects of cardiomyopathy and retinal toxicity. It probably goes without saying, but no one should attempt to obtain these medicines or any other potential COVID-19 treatments except through their physician. The benefit here is still unclear with limited published data and a lot left to learn.

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Correct.  It's a potential risk vs potential benefit decision.  Since the chloroquine exposure should be brief  (5-10 days tops), that should help reduce the risk of side effects vs longer term use.  Chloroquine has been around a long time and from I gather has been taken by tens of millions of people.  If the incidence of dangerous side effects were particularly substantial, healthy people wouldn't be taking it for prophylaxis against parasites all these years.  There's obvious contraindications related to cardiac condition and combining with other meds that could disrupt your heart rhythm.  Getting the sign-off by your physician first is important.  I presented mine with emerging medical publications, albeit absent controlled studies, and they understood and supported having a small amount on hand, with a hope to be able to discard it later without use.  I just planned on holding it in the event I contracted coronavirus.  We're neighbors with WA and Portland metro was one of the top 3-5 hot spots in the US even two weeks ago.  67% of the state's cases are within a 15-20 min drive of me in three directions.  Felt like invasion of the body snatchers the last two weeks because I understood what was already present.  My breathing symptoms are in a holding pattern and been obvious for 4 days now.  It feels like it could get worse but it hasn't yet.  I do think I'm going to be ok from whatever this is (not able to get tested for confirmation).  fwiw Ive never had pneumonia, dont smoke and can't remember the last time I had anything resembling chest involvement with any bug.  Chloroquine with zinc may not be doing anything, just don't know.  I'd start taking some zinc alone in advance regardless.

Posted
  On 3/15/2020 at 9:36 PM, Walden Ponderer said:

More cytokine storm discussion. Sounds like we should still home treat, but maybe see the Dr. sooner than previously thought: get the immune system stuff under control at the first hint of pneumonia:

 

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^^^^ hugely important.  This is how we keep people from getting on vents, dying, or even surviving but with lasting lung damage during this pandemic.

Posted (edited)
  On 3/14/2020 at 9:17 PM, GRHorn said:

Everyone should take zinc supplements while this is going on. Little downside. Has demonstrated anti-viral activity. 

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Well, specific to covid-19, zinc has no mechanism to penetrate the cell without chloroquine to essentially escort it into the cell. Correct?

Further, US doesn't regulate supplements much so hard to say what is included in your zinc supplement and if it has any capability to be successful.

Edited by pacman
Posted
  On 3/15/2020 at 10:08 PM, pacman said:

Well, specific to covid-19, zinc has no mechanism to penetrate the cell without chloroquine to essentially escort it into the cell. Correct?

Further, US doesn't regulate supplements much so hard to say what is included in your zinc supplement and if it has any capability to be successful.

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Boosting your zinc will have an effect of increasing intracellular zinc, just not 1:1 equillibrium.  Chloroquine in one study I saw referenced carries zinc across cell membrane to increase it about x10.  It sounds like if a person takes chloroquine alone, the extracellular zinc that is already normally present without supplement might be enough to boost intracellular levels for a clinical benefit, but I don't know.

also, the devastating immune response setting in 5-6 days after fever breaks is scary as hell.  I'm day1-2 since last chills/sweats.  Got my pcp on speed dial for that -umab if I go down.

Posted

I haven't checked lately, but LifeExtension.com sells zinc. I get multivitamins and Omega-3 from them, but I occasionally refill on other miscellaneous OTC pills.

Their follow up mailings and marketing materials are irritating, but paper can be recycled.

Posted (edited)

We're going to be hearing contradictory information and assertions that ultimately will be found to not be valid.  So don't take anything to the bank.

The comments to this contain some compelling thoughts:

 

 

Sinclair again with more on Chloroquine and Covid-19 (mixed/contradictory).  Also interesting info in the comments:

The comment about Cloroquine being most effective in the early initial stages of Covid-19 infection caught my attention.  It intuitively makes sense.  If you can slow or disrupt the early viral replication, you give your own defenses a chance to really hobble it at the inception.  Once complications form later, or the size of the infection becomes too large, chloroquine may not hurt and might still offer some help, but simply not be able to tip the scales nearly as much.  Again still some clinical advocates speaking up.  Also a French Chloroquine trial underway per comments.

 

Edited by triplehorn
Posted (edited)

steroids as a "definite no" seems like an absolute statement.  i think the first 11 cases in IL were all women, though I could be absolutely wrong.  i'm simply throwing shit at a wall to see if it sticks, and also, would like some DHT.  also, DHT is the best form of medicine (this is probably the most inaccurate term) to prevent aging.  if anyone has samples and is looking for a willing participant, PM ME.

another also, it is my understanding that DHT can only be obtained be dead people.  and their sperm that still resides.  so, the cycle of life can be put to use here?

Edited by Hmmm
Posted (edited)

Related to the tweet just above about a possible association between NSAIDS and young patients w Covid-19 who need ICU level of care, I wonder how much that affects older patients who seem so vulnerable?  I’d think on average more older folks would be taking aspirin, ibuprofen, naproxen etc. for general aches and pains from aging joints, not to mention aspirin for vascular protective purposes.   
 

NSAIDS May cause upregulation of ACE2 cell surface receptors ?  That’s like making a can’t miss rapid hit target for a virus, and lots of targets for lots of viruses all at once - potentially a dangerous accelerant for the infection from the start.

i have an allergy to NSAIDS, so maybe it cuts both ways for once.

 

Edited by triplehorn
Posted
  On 3/16/2020 at 4:55 AM, triplehorn said:

It intuitively makes sense.  If you can slow or disrupt the early viral replication,

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This does make sense. Maybe in the same way a neuraminidase inhibitor works on influenza to halt replication or nucleoside analogs to halt herpes replication.  If you have significant replication already then the zinc/hydroxychloroquine may not be beneficial. I have also read about corticosteroids not being effective. 

Posted

This appears on PubMed re Chloroquine for Covid-19

  Quote

Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):185-188. doi: 10.3760/cma.j.issn.1001-0939.2020.03.009.
[Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia].


[Article in Chinese; Abstract available in Chinese from the publisher]

multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia.

Abstract

in English, Chinese
At the end of December 2019, a novel coronavirus (COVID-19) caused an outbreak in Wuhan, and has quickly spread to all provinces in China and 26 other countries around the world, leading to a serious situation for epidemic prevention. So far, there is still no specific medicine. Previous studies have shown that chloroquine phosphate (chloroquine) had a wide range of antiviral effects, including anti-coronavirus. Here we found that treating the patients diagnosed as novel coronavirus pneumonia with chloroquine might improve the success rate of treatment, shorten hospital stay and improve patient outcome. In order to guide and regulate the use of chloroquine in patients with novel coronavirus pneumonia, the multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia developed this expert consensus after extensive discussion. It recommended chloroquine phosphate tablet, 500mg twice per day for 10 days for patients diagnosed as mild, moderate and severe cases of novel coronavirus pneumonia and without contraindications to chloroquine.



KEYWORDS:

Chloroquine; Novel coronavirus pneumonia


PMID:32164085DOI:10.3760/cma.j.issn.1001-0939.2020.03.009
 

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Posted (edited)

I don't like posting unofficial medical related stuff, but the NSAIDS/Covid-19 worsened course to complications association seems to be getting some traction.  If you don't need to take them and are facing exposure (basically all of us) seems reasonable to consider avoiding them right now:

 

 

Edited by triplehorn
  • Like 1
Posted
  On 3/16/2020 at 2:03 PM, triplehorn said:

I don't like posting unofficial medical related stuff, but the NSAIDS/Covid-19 worsened course to complications association seems to be getting some traction.  If you don't need to take them and are facing exposure (basically all of us) seems reasonable to consider avoiding them right now:

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Thanks for posting all the info on NSAIDs today. I unfortunately took 2 ibuprofen this morning but from this point forward I'm gonna tolerate a little muscle soreness and avoid NSAIDs, at least until we know more.

Posted (edited)
  On 3/15/2020 at 11:51 PM, Anastasis said:

I only have 50 rapid dissolve zinc tablets for a family of 5. 

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Try GNC; as of today, they're still selling Zinc (a "100-day supply" bottle of 30mg/serving) online as of this morning.

Edited by Dutch
Posted

Just a total wild assed guess but it could be that NSAIDs lower fever and you want to run a fever to kill off the virus (as long as it's not super high like 103+). Right? 

I'm no doctor though. 

Posted (edited)
  On 3/16/2020 at 4:06 PM, The Dog said:

Just a total wild assed guess but it could be that NSAIDs lower fever and you want to run a fever to kill off the virus (as long as it's not super high like 103+). Right? 

I'm no doctor though. 

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Yeah, it's only an initially observed association without any established cause and effect.  But the world is adjusting on the fly right now.  These kinds of timely initial observations can later prove to be extremely important.  With cases over 65y/o, there are probably multiple contributing risk factors for bad complications/outcomes.  Since risk factors are comparatively limited for young people, for this NSAID association to jump out in young people, it might be sharply narrowing the focus.  It very well could be that not taking NSAIDS has a similar risk reducing effect for 65+ y/o though other risk factors may not be so easily overcome.  For the immediate short term, I'd pass it along to avoid all NSAIDS unless a prescribing physician tells you the risks of not taking them outweigh the unknowns.

 

Edited by triplehorn
Posted

Well, fucking hell. For years and years, aspirin has been my preferred OTC of choice because it just plain works better for aches, pains, fevers, etc. for me. Tylenol doesn't do diddly squat unless I take more than I should, which I instinctively know not to do.

I've got a feeling if I get the snaky-sneezies, any fever reduction I'm going to be doing is going to take the form of ice-baths, because a fever over 103°F ain't gonna be kicked by Tylenol. My body just doesn't respond to the stuff for whatever reason.

Posted

For anyone who missed it, the first vaccine injections took place yesterday. Vaccine is produced by Moderna and will be a trial of 45 young healthy patients with the goal of determining safety. There are 3 different doses of the vaccine that will be given to 15 patients each.

https://www.nytimes.com/2020/03/16/health/coronavirus-vaccine.html

  Reveal hidden contents

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Posted
  On 3/16/2020 at 3:38 PM, Dutch said:

Try GNC; as of today, they're still selling Zinc (a "100-day supply" bottle of 30mg/serving) online as of this morning.

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At some point when people were discussing this previously, the claim was made that zinc is only beneficial in lozenge form – that its palliative properties derive from the interaction between the zinc and the lining of the throat. In other words, zinc in pill form is ineffective against viruses. 

Would anyone in the know have an opinion? 

Posted
  On 3/16/2020 at 4:06 PM, The Dog said:

Just a total wild assed guess but it could be that NSAIDs lower fever and you want to run a fever to kill off the virus (as long as it's not super high like 103+). Right? 

I'm no doctor though. 

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Well, neither is Triplehorn, so I'm not sure I'd take his advice seriously either.

Posted
  On 3/15/2020 at 9:57 PM, triplehorn said:

^^^^ hugely important.  This is how we keep people from getting on vents, dying, or even surviving but with lasting lung damage during this pandemic.

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The link is gone but I’m curious how they think “cytokine storm” can be modulated in the case of this virus. It’s just another name or iteration of SIRS. People’s immune systems react differently to infections. We don’t exactly know why some people get just sick, and some people go into shock and multi organ failure. This virus is rough because you can’t treat the underlying infection like you can a bacterial infection to get out of the woods. 

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