COVID-19 medical discussion

[drt 640]

19 minutes ago, triplehorn said:

Where'd you see she's not practicing?  link would be great.  She's describing her own experience treating patients.  That website you linked indicates she's active and practicing on the ER frontlines today.   

Looking at this without political bias, I can't find anything I disagree with in that interview about basically all the areas she speaks about, especially re safety. On masks, I wouldn't characterize what she said in the interview as anti-mask because she doesn't discourage use, but she clearly doesn't see that as the answer alone.  

 

 

[triplehorn 2,664]

You'd think I'm red hatter, huh.  Across 3 states, of the multiple docs I know who are prescribing this for their patients, or who have a prescription on hand for themselves in the event they do catch Covid, not a single one is a Trumper.  This is about medically informed pragmatism.    

If I lived in Texas where docs can freely prescribe this regimen off label for covid, and if I were of an age and had a medical history that put me at relatively higher risk of complicated illness, I would seek it to have it on hand in the event I got infected or request it if I got sick.  Personally, even if there are outstanding questions needing clarification about best use for covid, it's not a hard choice at all because it all starts with safety.  The safety scare in the US has to be the biggest charade affecting the practice of medicine I've ever witnessed.  It's really saddening to observe in real time.

[drt 640]

I specifically didn’t highlight the word political. I don’t give a shit about the politics. You admittedly have a bias and ignore evidence based medicine that has the significant potential for patient harm. 

[JohnLocke 115]

3 hours ago, triplehorn said:

 

Your first criticism of the study should be 

 

There's a LOT of positive studies out: https://c19study.com/   - site is updated with new studies regularly as they become available.  Negative studies are listed as well.

 

Really helpful conversation about safety, why a drug is OTC or not, off-label prescribing and what it means, and how the invisible hand of business and politics on health care decisions between physicians and patients in this pandemic are making matters much worse.  People are being denied a treatment that many studies show works, that over 2 dozen nations are widely employing with apparent major benefit, all when health side effects are negligible.  This ER doc gets it:

 

 

 

Yeah, I don't get why people are so closed minded about this. Good video, thanks. It's not just the fringe medical community on this. Here's a Yale epidemiologist saying widespread use could save tens of thousands of lives in the U.S.: https://www.foxnews.com/media/hydroxychloroquine-could-save-lives-ingraham-yale-professor

We need something better, but HCQ is safe, and appears to be the best we've got right now to take on an outpatient basis.

 

 

[JohnLocke 115]

On 7/19/2020 at 8:31 PM, PenelopeWitherspoon said:

https://www.yahoo.com/news/m/a231cd65-0f1c-31fb-bb2f-52a6ff32742f/cholesterol-lowering-drug.html

This is very interesting.  And could be very, very positive if it pans out.

I'd love to see this turn into something; surprisingly little info out there on it.

[triplehorn 2,664]

6 hours ago, JohnLocke said:

Yeah, I don't get why people are so closed minded about this. Good video, thanks. It's not just the fringe medical community on this. Here's a Yale epidemiologist saying widespread use could save tens of thousands of lives in the U.S.: https://www.foxnews.com/media/hydroxychloroquine-could-save-lives-ingraham-yale-professor

We need something better, but HCQ is safe, and appears to be the best we've got right now to take on an outpatient basis.

 

 

 Yes.  thank you.  

In the same vein, the Florida Broward retrospective Ivermectin results are now out:  

Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19

Findings show a significant mortality benefit in severe cases, but statistical significance not reached on more moderate cases.

Listen to this interview with Drs. Jean-Jacques Rajter and Dr. Juliana Cepelowicz Rajter as they discuss Ivermectin In Broward County and their experience from inception.  Check out what they talk about re politics and forces they encountered related to big pharma starting at 13:30 and 23:30 as well as their message in the final few minutes. 

Quote

 

 

 

It's sad that given we are lacking organized non-corrupt guidance at the federal level, what that also means is that we really are adrift and subject to the influence of forces aligned with maximizing profit, not saving lives.  This story is no different than what has been observed with HCQ in the US.  It starts with physicians treating actual patients and using trial and error within established safety bounds to understand if and how to help.  When motivated physicians directly involved in saving lives find something offers material benefit, and it's not in the financial interest of big pharma's financial bottom line, pharma moves its well oiled levers at their disposal to manipulate public perception, influence actions of federal bodies like the FDA, and gum up the works for peer reviewed publication.  Sounds sinister, but hey, it's just money they're after, not making actual life decisions for sick patients.

[Anastasis 23,471]

Ivermectin is an interesting candidate.  One of the aspects discussed in the article I linked at the top of this patient is that chasing HCQ  round and round exhausted a lot of resources that could have been used to trial other candidate drugs. 

[washparkhorn 9,939]

No surprise - Public Health/Psychology Research:

Narcissists and Psychopaths less likely to wear masks. 

Full Text: https://reader.elsevier.com/reader/sd/pii/S0191886920304219?token=DCBF57BDA32775C95C9A2A33380EBFC6CE8DAA47F5BB5EEB6BFB1F70F8240EA7B13C8FDD3E41946B31530F26493BD05A

(Click download PDF for full text)

Edited July 23, 2020 by washparkhorn

[Bevo 13,609]

7 hours ago, washparkhorn said:

No surprise - Public Health/Psychology Research:

Narcissists and Psychopaths less likely to wear masks.

So basically if Michael Myers comes into my neighborhood we are double fucked

[BradInATX 9,208]

Fuck me, they're multiplying.

[Liquor and Poker 3,659]

8 hours ago, washparkhorn said:

No surprise - Public Health/Psychology Research:

Narcissists and Psychopaths less likely to wear masks. 

Full Text: https://reader.elsevier.com/reader/sd/pii/S0191886920304219?token=DCBF57BDA32775C95C9A2A33380EBFC6CE8DAA47F5BB5EEB6BFB1F70F8240EA7B13C8FDD3E41946B31530F26493BD05A

(Click download PDF for full text)

This proves my long-standing belief that something like 90% of White UMC Americans are narcissists and psychopaths. 

[triplehorn 2,664]

23 hours ago, JohnLocke said:

Yeah, I don't get why people are so closed minded about this. Good video, thanks. It's not just the fringe medical community on this. Here's a Yale epidemiologist saying widespread use could save tens of thousands of lives in the U.S.: https://www.foxnews.com/media/hydroxychloroquine-could-save-lives-ingraham-yale-professor

We need something better, but HCQ is safe, and appears to be the best we've got right now to take on an outpatient basis.

 

 

I want to follow up on your Risch interview.  This morning the Yale prof had an op-ed published in Newsweek: The Key to Defeating COVID-19 Already Exists. We Need to Start Using It

Risch makes a reference to and explains what was recently observed in Switzerland.  France Soir did a story on this .  The graphic explains it pretty clearly:

 

On big pharma (this case in particular, Gilead😞

"Now primarily a marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in its way, including the U.S. Congress, the Food and Drug Administration, academic medical centers, and the medical profession itself."

- Marcia Angell, former editor-in-chief of the NEJM, The Truth About the Drug Companies

 

Edited July 23, 2020 by triplehorn

[XYZ 2,154]

Pharma, oil, tobacco, banks...it's all the same. They bribe the government and they get special treatment. Their executives never go to prison.

[JohnLocke 115]

5 hours ago, triplehorn said:

I want to follow up on your Risch interview.  This morning the Yale prof had an op-ed published in Newsweek: The Key to Defeating COVID-19 Already Exists. We Need to Start Using It

Risch makes a reference to and explains what was recently observed in Switzerland.  France Soir did a story on this .  The graphic explains it pretty clearly:

 

On big pharma (this case in particular, Gilead😞

"Now primarily a marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in its way, including the U.S. Congress, the Food and Drug Administration, academic medical centers, and the medical profession itself."

- Marcia Angell, former editor-in-chief of the NEJM, The Truth About the Drug Companies

 

It's good that a guy like Dr. Risch is speaking out; it will have an effect.  I'd hope they fast-tract some studies on Ivermectin.  Those Broward results were really good.

[Anastasis 23,471]

I wonder how long they had to torture those data to come up with that graph. 

Here are Swiss daily deaths, most of the dates during the period 27 May to 05 June are 0 deaths.

 

[triplehorn 2,664]

Paper on observational study that shows how critical sufficient levels of Vit D are to weather Covid infection:

Vitamin D Sufficiency Reduced Risk for Morbidity and Mortality in COVID-19 Patients

 

Quote

Method: Hospital medical records were analyzed from inpatient database of Sina Hospital COVID-19 Registry (SHCo-19R). The data include demographics, laboratory measurements and computerized tomography results. Vitamin D sufficiency was defined a serum 25-hydroxyvitamin D [25(OH)D] level of at least 30ng/mL.

Results: The hospital data of 235 patients infected with COVID-19 were analyzed. The mean age was 58·7 years ± 15·2 SD. Based on CDC criteria, among our study patients, 74% had severe COVID-19 infection and 32·8% were vitamin D sufficient [25(OH)D≥30 ng/mL]. After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality, serum levels of C-reactive protein (CRP)and an increase in lymphocyte percentage Only 9·7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/mL.

Discussion: The significant reduction in serum CRP, an inflammatory marker, along with increased lymphocytes percentage suggest that vitamin D sufficiency also may help modulate the immune response possibly by reducing risk for cytokine storm in response to this viral infection. Therefore, it is recommended that improving vitamin D status in the general population and in particular hospitalized patients has a potential benefit in reducing the severity of morbidities and mortality associated with acquiring COVID-19.

 

 

[triplehorn 2,664]

Generic over-the-counter mucolytic medication, bromhexine, showing signs of efficacy against Covid in this RCT in Iran with collab from U of Arizona and U of Toronto:

Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial

Note these are patients who already have progressed to advanced illness/pneumonia.

 

 

Mechanism of action thought to be inhibition of TMPRSS2 transmembrane protease involved in viral entry to cell via ACE2 receptor.  This is a different path of inhibition than other agents under investigation, which means it potentially could be used in combination with other meds/mechs of action to achieve a greater therapeutic effect.

 

 

Used safely in adults and children

[Rip76 4,974]

This should provide for some real fun at work, when you’ve already made someone sit out for 28 days.

https://www.nbcnews.com/health/health-news/cdc-changes-covid-19-guidance-how-long-patients-need-be-n1234883

 

[Anastasis 23,471]

Amazing how much trial bandwidth has been wasted...

https://www.medrxiv.org/content/10.1101/2020.07.20.20157651v1

Abstract

Background Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited to non-pharmacological interventions. Hydroxychloroquine (HCQ) has been proposed as a postexposure therapy to prevent Coronavirus disease 2019 (Covid-19) but definitive evidence is lacking. Methods We conducted an open-label, cluster-randomized trial including asymptomatic contacts exposed to a PCR-positive Covid-19 case in Catalonia, Spain. Clusters were randomized to receive no specific therapy (control arm) or HCQ 800mg once, followed by 400mg daily for 6 days (intervention arm). The primary outcome was PCR-confirmed symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, either symptomatically compatible or a PCR-positive result regardless of symptoms. Adverse events (AEs) were assessed up to 28 days. Results The analysis included 2,314 healthy contacts of 672 Covid-19 index cases identified between Mar 17 and Apr 28, 2020. A total of 1,198 were randomly allocated to usual care and 1,116 to HCQ therapy. There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ). The incidence of AEs was higher in the intervention arm than in the control arm (5.9% usual care vs 51.6% HCQ), but no treatment-related serious AEs were reported. Conclusions Postexposure therapy with HCQ did not prevent SARS-CoV-2 disease and infection in healthy individuals exposed to a PCR-positive case. Our findings do not support HCQ as postexposure prophylaxis for Covid-19.

[triplehorn 2,664]

Here's a follow-up article to the large Israeli study demonstrating the importance of sufficient Vit D levels for fighting/limiting Covid infection:

Vitamin D helps us fight Covid-19, major study finds - Israeli population-based study supports research showing that vitamin D supplements could help people avoid serious respiratory effects of Covid-19.

Quote

A low level of vitamin D in blood plasma appears to be an independent risk factor for Covid-19 infection and hospitalization, say scientists from Israeli HMO Leumit Health Services and the Azrieli Faculty of Medicine of Bar-Ilan University.

The researchers came to their conclusion using real-world data and an Israeli cohort of 782 Covid-19 positive patients and 7,025 Covid-19 negative patients.

“The main finding of our study was the significant association of low plasma vitamin D level with the likelihood of Covid-19 infection among patients who were tested for Covid-19, even after adjustment for age, gender, socio-economic status and chronic, mental and physical disorders,” said Dr. Eugene Merzon, head of Leumit’s Department of Managed Care.

“Furthermore, low vitamin D level was associated with the risk of hospitalization due to Covid-19 infection, although this association wasn’t significant after adjustment for other factors,” he added.

The scientists’ research follows a few worldwide studies that have shown the pronounced impact of vitamin D metabolites on the immune system response and on the development of Covid-19 infection by the novel SARS CoV-2 coronavirus.

“Our finding is in agreement with the results of previous studies in the field. Reduced risk of acute respiratory tract infection following vitamin D supplementation has been reported,” said Dr. Ilan Green, head of Leumit’s Research Institute.

As for the amount of vitamin D required, Merzon says it should be “personalized and take into account patients’ age, gender, race and ethnicity, nutritional status and health condition.”

Their report on the study was published in The FEBS Journal and is expected to make a wide impact because of the study’s size and population-based structure.

Fascinating findings

Dr. Milana Frenkel-Morgenstern, leader of the Azrieli Faculty of Medicine research group, added that the analysis showed people who were Covid-19 positive were older than non-infected people.

“Interestingly, the two-peak distributions for age groups were demonstrated to confer increased risk for Covid-19: around ages 25 and 50 years old,” she said.

“The first peak may be explained by high social gathering habits at the young age. The peak at age 50 years may be explained by continued social habits, in conjunction with various chronic diseases.”

Leumit Chief Medical Officer Dr. Shlomo Vinker said he was surprised to discover that “chronic medical conditions, like dementia, cardiovascular disease and chronic lung disease that were considered to be very risky in previous studies, were not found as increasing the rate of infection in our study.”

However, he added, “this finding is highly biased by the severe social contacts restrictions that were imposed on all the population during the Covid-19 outbreak. Therefore, we assume that following the Israeli Ministry of Health instructions, patients with chronic medical conditions significantly reduced their social contacts. This might indeed minimize the risk of Covid-19 infection in that group of patients.”

Now this joint Israeli research team is planning to evaluate factors associated with Covid-19 mortality in Israel.

“We are willing to find associations to the Covid-19 clinical outcomes — for example, pre-infection glycemic control of Covid-19 patients — to make the assessment of mortality risk due to Covid-19 infection in Israel,” said Merzon.

 

While there is a lot of attention being paid to adaptive immunity, like antibody formation, it's important to keep in mind the essential role T cell mediated immunity plays in fighting novel infections.  Adequate Vit D levels play a significant role in T cell mediated immune responses.

I saw this graph depicting the relationship between Vit D blood levels and Covid infection:

 

 

The pink column represents normal range (ie 30 ng/mL).  For general purposes, taking 5000 IU of Vit D3 should get you at and above 30ng/mL within a few weeks if your levels are insufficient.  There is a potential for Vit D toxicity at levels above ~150 ng/mL but that is very rare and seems to happen only with gross misadministration.  Blood level testing is a good idea if folks are on prolonged high dose Vit D.

So adding any med that can even slow the rate of viral replication might allow enough time for a decisive T cell mediated victory over Covid with adequate Vit D.  Just a hunch, but I don't think the T Cell immunity just snaps into peak function with a loading dose of Vit D in those who are deficient.  There's likely a sequence of cellular/molecular events that take days to weeks to correct to optimize the role for immune response.

 

Edited July 27, 2020 by triplehorn

[Anastasis 23,471]

Cross-posting, since this is the more appropriate place for it.

This article explains why initial in vitro reports of SARS activity based on cell cultures was a head fake, and why the clinical data just hasn't borne out the initial signal.  

 

Why hydroxychloroquine and chloroquine don’t block coronavirus infection of human lung cells

The new study was carried out by scientists in Germany who tested HCQ on a collection of different cell types to figure out why this drug doesn’t prevent the virus from infecting humans.

Their findings clearly show that that HQC can block the coronavirus from infecting kidney cells from the African green monkey. But it does not inhibit the virus in human lung cells – the primary site of infection for the SARS-CoV-2 virus.

In order for the virus to enter a cell, it can do so by two mechanisms - one, when the SARS-CoV-2 spike protein attaches to the ACE2 receptor and inserts its genetic material into the cell. In the second mechanism, the virus is absorbed into some special compartments in cells called endosomes.

Depending on the cell type, some, like kidney cells, need an enzyme called cathepsin L for the virus to successfully infect them. In lung cells, however, an enzyme called TMPRSS2 (on the cell surface) is necessary. Cathepsin L requires an acidic environment to function and allow the virus to infect the cell, while TMPRSS2 does not.

In the green monkey kidney cells, both hydroxychloroquine and chloroquine decrease the acidity, which then disables the cathepsin L enzyme, blocking the virus from infecting the monkey cells. In human lung cells, which have very low levels of cathepsin L enzyme, the virus uses the enzyme TMPRSS2 to enter the cell. But because that enzyme is not controlled by acidity, neither HCQ and CQ can block the SARS-CoV-2 from infecting the lungs or stop the virus from replicating.

https://theconversation.com/why-hydroxychloroquine-and-chloroquine-dont-block-coronavirus-infection-of-human-lung-cells-143234

https://www.nature.com/articles/s41586-020-2575-3

[triplehorn 2,664]

This is damn horrific - study shows almost 8 of 10 infected with covid have persisting cardiac abnormalities irrespective of health status or severity of illness.

JAMA: Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)
 

- 78% of Covid-19 patients had abnormal cardiac markers “independent of preexisting conditions, severity [illness]"

-Cardiac function remains impaired in most recovered patients, even middle aged people.

-Lymphocytes can invade the heart, causing edema and fibrosis.  Cardiac fibrosis.

-Persisting impaired cardiac function nearly as likely in outpatient cases as hospital cases.

 

 

Edited July 29, 2020 by triplehorn

[Newdoc 3,457]

On 7/26/2020 at 10:11 PM, Anastasis said:

Our findings do not support HCQ as postexposure prophylaxis for Covid-19.

Don’t tell this to the “the video has been blocked!” crowd. Dr. Stella has said different and confirmation bias be damned.

On 7/27/2020 at 3:58 PM, triplehorn said:

sufficient Vit D levels for fighting/limiting Covid infection:

We’ve known this for at least a few weeks now. Maybe we should put up a video and get it banned so the no mask, it’s a hoax crowd will start taking it.

[Newdoc 3,457]

53 minutes ago, triplehorn said:

study shows almost 8 of 10 infected with covid have persisting cardiac abnormalities irrespective of health status or severity of illness.

The authors are forthcoming but there a number of limitations to this study. It’s more of a “oh crap” “we better increase the study size and length” study. With the heart’s ability to remodel, I would be interested to see cardiac function at 12 and 24 months past infection.

[Brisketexan 105,479]

7 minutes ago, Newdoc said:

The authors are forthcoming but there a number of limitations to this study. It’s more of a “oh crap” “we better increase the study size and length” study. With the heart’s ability to remodel, I would be interested to see cardiac function at 12 and 24 months past infection.

"Remodeling my heart" sounds like something my wife asked me to do in marriage counseling.

I mean, I did.  Put up some blackout shades and installed a big screen TV, because my heart likes things dark, with cheap entertainment.

[utee94 15,877]

Remodel my heart isn't near as catchy as...
 

 

 

[Surly Bevo 25,256]

10 minutes ago, Brisketexan said:

"Remodeling my heart" sounds like something my wife asked me to do in marriage counseling.

I mean, I did.  Put up some blackout shades and installed a big screen TV, because my heart likes things dark, with cheap entertainment.

Remodel My Heart.  Motley Lou smash single

[Anastasis 23,471]

I believe that @Fat Bastard is a cardiologist.  Perhaps he would care to comment on the relevance of the results in the JAMA publication linked up thread?

[horncyclist 1,391]

3 hours ago, triplehorn said:

This is damn horrific - study shows almost 8 of 10 infected with covid have persisting cardiac abnormalities irrespective of health status or severity of illness.

JAMA: Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)
 

- 78% of Covid-19 patients had abnormal cardiac markers “independent of preexisting conditions, severity [illness]"

-Cardiac function remains impaired in most recovered patients, even middle aged people.

-Lymphocytes can invade the heart, causing edema and fibrosis.  Cardiac fibrosis.

-Persisting impaired cardiac function nearly as likely in outpatient cases as hospital cases.

 

 

I came here to see if there was any discussion of this. That's terrifying. One of the two personal contacts I know who have had Covid is a woman in her 50s with no complications who has had serious cardiac problems after having Covid. Information like this really changes the personal risk calculation and if more people were aware of these risks, we would hopefully be taking this much more seriously. Interested in the limitations of the study.

[triplehorn 2,664]

This intra-Yale collab just yielded some amazing insights with potential immediate impact on clinical decision making:

Longitudinal analyses reveal immunological misfiring in severe COVID-19

this entire twitter thread is an ultra-dense cliffs notes of the above article by one of the PI's an worth close consideration:

 

 

excerpted tweet:

 

The last tweet stands out ---> one key feature of severe disease formation is low T cell number.  Should make you go straight to thinking about the role of Vit D here.   Quick reference points to Vit D levels playing a role in T cell numbers and modulating T cell function, and may induce many different anti-inflammatory functions.  Read that correctly, anti-inflammatory, or the opposite of having an immune response run amok, ie what we've come to associate with with severe disease formation in covid.  See general discussion:  The Link.

They then progressed to identifying 3 clusters of patients based on 4 immune signatures leading to the ability to form new targets for early diagnostic recognition that could also better inform specific types of early intervention revealed by those immune signatures.

 

 

Edited July 30, 2020 by triplehorn

[JohnLocke 115]

8 hours ago, triplehorn said:

This is damn horrific - study shows almost 8 of 10 infected with covid have persisting cardiac abnormalities irrespective of health status or severity of illness.

JAMA: Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)
 

- 78% of Covid-19 patients had abnormal cardiac markers “independent of preexisting conditions, severity [illness]"

-Cardiac function remains impaired in most recovered patients, even middle aged people.

-Lymphocytes can invade the heart, causing edema and fibrosis.  Cardiac fibrosis.

-Persisting impaired cardiac function nearly as likely in outpatient cases as hospital cases.

 

 

Well, that's extra horrifying. Thanks for spoiling my day.

spider eating a possum, in case you were wondering.

Edited July 30, 2020 by JohnLocke

[triplehorn 2,664]

Following up on the Yale collab above, notice the attention Dr. Iwasaki pays to "inflammasomes" : 

Quote

 

"Also, our trajectory analyses raise the possibility that early interventions that target inflammatory markers that are predictive of worse disease outcome would be more beneficial than targeting late-appearing cytokines. 👀 at you #inflammasomes (15/n)"

"The serum cytokines indicate the activation of inflammasomes based on elevated cytokines IL-18 and IL-1b, as well as IL-6. [...] (4/n)."

 

Inflammasomes are non-membrane bound cytosolic protein complexes that appear to be associated with a variation of programmed cell death called pyroptosis.  Pyroptosis is a highly inflammatory form of cell death often associated with intracellular pathogens - like viruses and certain bacteria.

Here's a graphic of inflammosomal activation (hook'em UT Southwestern). Note the release of IL-18 and IL-1b.  The pinwheel stucture is the inflammasome (originally characterized around 2002).  Also note the association with cytosolic lysosomes (membrane bound organelle):

 

So maybe it would be helpful, if not extremely helpful, if we could find a way to attenuate the role of Covid associated inflammasome activation and cell death to reduce the cascade resulting in tissue and multiple organ damage observed with Covid. 

You had to know where I was going with this lol.  Naturally I wondered if there's a possibility that HCQ fits into this somewhere.  HCQ is generally thought of as inhibiting replication of Covid virus via a Zinc mechanism that inhibits viral RNA dependent RNA polymerase which has been clearly demonstrated in vitro.  But we also know HCQ has anti-inflammatory properties.  It's why it's used every day to treat Lupus and Rheumatoid Arthritis.  Every freaking day.  So where in the vast array of immune function does the anti-inflammatory mechanism of HCQ fit ?  

Turns out in this study Hydroxychloroquine attenuates renal ischemia/reperfusion injury by inhibiting cathepsin mediated NLRP3 inflammasome activation. 

Also from this research on rheumatologic mechanisms of action of Chloroquine and Hydoxychloroquine:

"These drugs interfere with lysosomal activity and autophagy, interact with membrane stability and alter signalling pathways and transcriptional activity, which can result in inhibition of cytokine production and modulation of certain co-stimulatory molecules."

Look again at the picture above.  Lysosomal activity works through the cathepsin and NLRP3 pathway to activate inflammosomes resulting in a highly inflammatory response with IL-18 and IL-1b.

So it appears the anti-inflammatory mechanism of CQ/HCQ has a direct and intimate tie to inhibiting a key pathway for multi-organ pathogenesis with Covid-19 that has just now been uncovered as crucial by the Yale collaboration I posted above.  Would this have potentially beneficial protective effects when applied pre-cytokine storm in Covid-19 infection?  Sure appears that way, and is consistent with clinical observations.

 

Edited July 30, 2020 by triplehorn

[Homercles 10,206]

Ok so what do we do about vitamin D levels?

[jimmyjazz 46,351]

8 minutes ago, Homercles said:

Ok so what do we do about vitamin D levels?

Sunshine and Vitamin D supplements.  I take the gummies.  (Seriously.)

[triplehorn 2,664]

Vit D appears to be essential for healthy and robust T cell function.  T cell immunity plays a frontline role in fighting novel infection when we don't have a jump start from antibody protection.  As we age, our immune system weakens and we lose our virus-killing fastball.  Basement dwelling fast food eating young people still do well on average because of youth.  However boosting Vit D in middle age and beyond appears to have a dramatic effect on squashing Covid infection earlier likely through a juiced up initial T cell immune function.  This likely applies to fighting multiple respiratory viruses.  I'm not much of a vitamin and supplement taker, but I started taking Vit D 5000 IU per day in early March along with Zinc and Vit C.  

edit: a caveat to Vit D and T cell function is that Vit D appears to help modulate T cell function, so this conceivably could also involve balancing an immune response, ie putting the brakes on an inflammatory response from running amok as we observe in complicated Covid illness.

 

Edited July 30, 2020 by triplehorn

[Newdoc 3,457]

5 minutes ago, jimmyjazz said:

Sunshine and Vitamin D supplements.  I take the gummies.  (Seriously.)

Both natural and supplemental vitamin D appear to be effective  in the early data. This is very good news as supplemental vitamin D is not so great in other conditions. And unlike Plaquenil, unless you jack your Vit D levels up, it is relatively safe to take.

[jimmyjazz 46,351]

10 minutes ago, Newdoc said:

Both natural and supplemental vitamin D appear to be effective  in the early data. This is very good news as supplemental vitamin D is not so great in other conditions. 

What are you referring to?  Would supplemental Vitamin D be contraindicated for, say, myopic short middle age men with a bad temper and a fondness for beer?

[GreenspointTexas 9,708]

22 hours ago, Anastasis said:

I believe that @Fat Bastard is a cardiologist.  Perhaps he would care to comment on the relevance of the results in the JAMA publication linked up thread?

Im not a cardiologist, but these numbers dont look that bad?

 

 

also, ive been taking Vitamin D (5000 iu), Quercitin, and a Vitamin C/Zinc combo since March

 

i suggest everyone without kidney/liver failure to do the same

[Newdoc 3,457]

1 minute ago, jimmyjazz said:

What are you referring to?  Would supplemental Vitamin D be contraindicated for, say, myopic short middle age men with a bad temper and a fondness for beer?

Vitamin D in its supplemental form is not a panacea for bone health, depression and a myriad list of other things that people jumped onto several years ago when they thought vitamin D was the next snake oil.

[Homercles 10,206]

Ok so I need to buy vitamin D supplements?  40yo moderately overweight guy here...my young kids bring everything home with them so over the years I feel my immune system has been pretty strong due to sheer volume.  

[utee94 15,877]

26 minutes ago, Newdoc said:

Vitamin D in its supplemental form is not a panacea for bone health, depression and a myriad list of other things that people jumped onto several years ago when they thought vitamin D was the next snake oil.

As always thanks for your medical insights.

So what would you prescribe as an appropriate dose per day/week/month for supplemental vitamin D in adults that really do not want to catch the Coronas?  Based on past advice from my doc, the 5000IU per day that triplehorn is taking seems really high?  

 

 

Edited July 30, 2020 by utee94

[Homercles 10,206]

11 minutes ago, utee94 said:

As always thanks for your medical insights.

So what would you prescribe as an appropriate dose per day/week/month for supplemental vitamin D in adults that really do not want to catch the Coronas?  Based on past advice from my doc, the 5000IU per day that triplehorn is taking seems really high?  

 

 

Who does want to catch it?

[Newdoc 3,457]

18 minutes ago, utee94 said:

As always thanks for your medical insights.

So what would you prescribe as an appropriate dose per day/week/month for supplemental vitamin D in adults that really do not want to catch the Coronas?  Based on past advice from my doc, the 5000IU per day that triplehorn is taking seems really high?  

 

 

5,000 ius maybe on the high side if you are already normal. You’re probably safe at 1000 ius a day but if you happen to be really low then that may not move the needle. Vitamin D levels over 30 ng/ml seem to confer good immune response.

The data doesn’t appear to show it prevents infection but rather allows an effective initial and robust immune response.

[utee94 15,877]

10 minutes ago, Homercles said:

Who does want to catch it?

The kids licking toilets and throwing COVID parties?

 

[XYZ 2,154]

10 minutes exposed to the sun, no sun screen (duh), and while the sun is high. Not sure how frequently, though.

[utee94 15,877]

1 minute ago, Newdoc said:

5,000 ius maybe on the high side if you are already normal. You’re probably safe at 1000 ius a day but if you happen to be really low then that may not move the needle. Vitamin D levels over 30 ng/ml seem to confer good immune response.

The data doesn’t appear to show it prevents infection but rather allows an effective initial and robust immune response.

Thanks!  And, since it can take weeks to show increased levels, sounds like this is something that builds up over time?  Is that how it works?

[XYZ 2,154]

I increased my vitamin D level from 17 to thirty-something by taking 2000 IUs per day.

[dcar00 14,438]

7 minutes ago, Newdoc said:

5,000 ius maybe on the high side if you are already normal. You’re probably safe at 1000 ius a day but if you happen to be really low then that may not move the needle. Vitamin D levels over 30 ng/ml seem to confer good immune response.

The data doesn’t appear to show it prevents infection but rather allows an effective initial and robust immune response.

my doc said 1000iu a day.  been doing that for 7 or 8 years plus a multivite.  I was only a bit low.

[triplehorn 2,664]

There's a rule of thumb that for every 1000 IU of Vit D3 you take, you can expect an increase in blood level by 10 ng/mL.  So 5000 IU/d sustained will likely bump you significantly above the general normal level of 30 ng/mL, but not really near the standard toxic level considered to be above 150 ng/mL.  If you look at this graph I linked last page, you see that even at a normal level of 30 ng/mL, a pretty siginifcant percentage of folks experienced Covid associated fatal demise (with an average age of 60y/o).  

Spoiler

 

So having a blood level in the 40-50 ng/mL range might be preferable to swimming around the 'normal' level of 30 while still not approaching anything considered toxic D3 levels.  I'll probably back off to 5000 IU every other day since I've been taking it long enough to sustain the boost (5000 IU daily since March).

edit: also re-posting this 2 week old pre-print from Lancet:

Vitamin D Sufficiency Reduced Risk for Morbidity and Mortality in COVID-19 Patients

 

Edited July 30, 2020 by triplehorn

[Fat Bastard 608]

On 7/29/2020 at 1:23 PM, Anastasis said:

I believe that @Fat Bastard is a cardiologist.  Perhaps he would care to comment on the relevance of the results in the JAMA publication linked up thread?

It’s very sobering data, tbh, and it’s making big news in our community, especially considering the downstream sequelae younger CV19 patients may have who did not require hospitalization. The good news regarding this study (admittedly from the abstract that I read) is that it was just radiographic findings with really zero clinical significance. The mean LVEF was still >55%, which is very promising. Of course, knowing that a very common etiology for nonischemic cardiomyopathy (NICMP) is viral illness, it’ll be very interesting to see the downstream effects of this virus especially if they have other CV risk factors.