It's completely predictable that the expensive drugs that Trump got (the monoclonal antibodies & Remdesivir) dominate the news cycle, while the cheap ones don't. From, the Physician to the President's report on October 2nd [0]:
>Following PCR-confirmation of the President’s diagnosis, as a precautionary measure he received a single 8 gram dose of Regeneron’s polyclonal antibody cocktail. He completed the infusion without incident. In addition to the polyclonal antibodies, the President has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin.
If there's a game changing drug for COVID-19 in there I'd say it was vitamin D.
We covered the Spanish randomized open label, double-masked clinical trial of vitamin D just over a month ago. [1][2]
>“Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) p value X2 Fischer test p < 0.001.”
The Internet Book of Critical Care is a collaborative effort by front-line docs to share information about promising therapies and approaches to COVID.
It's really interesting, and broken down by bullet points.
Check it out, and get an idea of how actual doctors in the field are approaching this thing.
Neither is anyone at my academic teaching hospital.
A lot of really smart people with decades of experience in the field, and a direct clinical role have collected a variety of approaches that seem to work. Unfortunately, none of them have characterized Vit D as a 'game changing drug.'
I think it might be wise to hold off on phrases like 'game changing' with regards to Vitamin D.
Not to say that it may not eventually play a role as part of a multifaceted approach.
Re: "game changer", I was referencing the comment by war1025 that polyclonal anti-bodies were a game changer.
>Sounds like Trump got a similar cocktail from a different company. The speed of his recovery and the fact that him having Coronavirus isn't even part of the news cycle anymore seems like a strong indicator that the treatment is probably a game changer.
>A lot of really smart people with decades of experience in the field, and a direct clinical role have collected a variety of approaches that seem to work. Unfortunately, none of them have characterized Vit D as a 'game changing drug.'
Sorry - I'm more impressed by a single randomized open label, double-masked clinical trial than I am by argument by authority. Perhaps we can check back here in a couple of years time ...
I can't help remembering how actual doctors in the field were telling us back in February to "get a flu shot", or "masks only work for doctors who've been trained to put them on properly". I'm so happy that I'd already purchased my N95 masks in January while you guys were asleep.
I advise you to scope out the definition of a pilot trial. Here's a cool one I found:
"A pilot trial is a small study conducted to help design and assess the feasibility of doing a larger, full‐scale trial. They also investigate whether the methods and procedures are able to obtain the data that is needed to answer the question that will be addressed in the larger study."
"Clinical trials are research studies performed in people that are aimed at evaluating a medical, surgical, or behavioral intervention. They are the primary way that researchers find out if a new treatment, like a new drug or diet or medical device (for example, a pacemaker) is safe and effective in people. Often a clinical trial is used to learn if a new treatment is more effective and/or has less harmful side effects than the standard treatment."
Getting a flu shot is important. Please get yours this season so we can help reduce the spread of yet another deadly respiratory virus that kills thousands of people each year.
There was a lot of debate about masks. As you can recall, a lot of frontline health professionals were dying because of a lack of PPE while carrying out
incredibly risky procedures like intubation.
Gondi, S., Beckman, A. L., Deveau, N., Raja, A. S., Ranney, M. L., Popkin, R., & He, S. (2020). Personal protective equipment needs in the USA during the COVID-19 pandemic. The Lancet, 395(10237), e90–e91. https://doi.org/10.1016/s0140-6736(20)31038-2
I'm happy that you have your N95 masks to keep you safe at Trader Joes (where all of us normal folks have been well-served with cloth masks and social distancing) because god forbid an emergency room nurse or doctor needed N95-level protection while securing a patient's airway after they stop breathing.
I don't know what you're implying by the phrase 'argument by authority,' but we're talking about people who have spent their entire careers in the field of medicine. Normally we call those people 'scientists' and 'experts.' I'd trust Dennis Richie to know a thing or two about C, and if I wanted to know a little something about algorithms I wouldn't be done a disservice by chatting with Donald Knuth.
Edit: I wrote this on my other comment too, but I wanted to put it here to make sure you saw it:
First of all I'd like to preface this by saying that everything I write is with a light heart, and I'm not actually 'angry' or feeling any sort of ill will towards you. Everything is weird now with COVID, and sometimes when we say stuff on the internet it might sound more aggressive than it is intended to. So, no matter what our different opinions are I love you dude, and if we were in person I'd buy you a beer.
>Getting a flu shot is important. Please get yours this season so we can help reduce the spread of yet another deadly respiratory virus that kills thousands of people each year.
It turns out that masks are far more effective than flu shots, so no, I'm not going to get a flu shot. Anyway, IIRC, "kills thousands of people each year" is a statistical projection that doesn't actually stand up to scrutiny. Certainly, it's nothing like COVID-19.
>There was a lot of debate about masks.
There was a lot of misinformation spread because of the failure to stockpile PPE. That misinformation is still doing harm now because the MAGA folks are running around saying "masks don't work"
>I don't know what you're implying by the phrase 'argument by authority,' but we're talking about people who have spent their entire careers in the field of medicine. Normally we call those people 'scientists' and 'experts.'
Unfortunately, medical experts credibility is now shot by spreading false information about masks, and by downplaying the risk of COVID-19 in January and February by telling everybody to get a flu shot. Then I wonder how many people died on ventilators when intubated on MAX ..
As a group you're weren't operating at the level of Dennis Richie or Donald Knuth, so you have work to do to regain credibility.
In fact, you're still not now. You should focus less on evidence-based medicine and more on risk asymmetry. Mask wearing (even of cloth masks) had very little downside and a potentially huge upside. But we had to wait for evidence. The same is true of vitamin-D now. Look for low-risk interventions. If we don't have the resources to mass test the at-risk population, we should encourage those on poor diets to take 1000IU a daythis winter. But we will have to wait until next year for evidence.
Wait, you do understand that people are saying to get the flu shot so people don't get the flu, right? They're not saying that the flu shot will protect you against COVID.
Where do you get your data about annual influenza deaths? If you have a good source, I'm willing to take a look.
It's important not only so you don't get sick, but also so you don't spread it to others who may have a weaker immune system. We're all in this together.
Please don't lump all health care personnel in with political appointees in Washington D.C.
Donald Knuth is a computer scientist, not the president's politically-appointed personal pet computer scientist.
>Wait, you do understand that people are saying to get the flu shot so people don't get the flu, right?
For sure, but I don't happen to agree. It was on the news here in Japan this morning - flu cases have pretty much disappeared this season - presumably because everyone is wearing masks.
>Where do you get your data about annual influenza deaths? If you have a good source, I'm willing to take a look.
I can look for it, but IIRC the several 10,000 annual influenza deaths are a statistical projection. There was an article somewhere from someone in ER during the peak of the COVID-19 deaths saying they had pretty much never seen an actual influenza death - and that was the experience of other people in ER - so there was a mismatch between the statistical projection and lived experience.
>It's important not only so you don't get sick, but also so you don't spread it to others who may have a weaker immune system. We're all in this together.
The best way to do that is to wear masks. Here in Japan - nobody here ever said that "masks don't work for non-medics who haven't been trained to put them on properly". So we don't now have the problem with lots of MAGA folks running around saying "masks don't work".
It would be wonderful if we were anywhere near as diligent with masks as folks in Japan have been.
Unfortunately, masks became a political issue here in a way that probably had nothing to do with those dumb CDC press releases. Masks were cleverly and intentionally linked to a sentiment of 'freedom' and 'fascism' in an almost astonishing way.
This kind of thing doesn't even raise eyebrows here anymore:
I don't know how much of it you've seen in Japan, but this country is divided, scared, and hopeless in a way that nobody I've talked to can claim to have experienced in their lifetime. People's family members are dying, people are losing their jobs, people are being evicted, people are losing their businesses, politicians are locked in a geriatric MMA grapple, and there's no vision for how we're getting out of this.
Actually, I'm generally pro-freedom where there is no obvious victim. But that's not true in this case. The way I see it is you can suffer the more modest loss of freedom of mask wearing now. Or you can ignore that and have lockdowns imposed on you later.
>Unfortunately, masks became a political issue here in a way that probably had nothing to do with those dumb CDC press releases.
You want to believe that, but I think in your heart you know that is not true. Those messages seeped into the public consciousness. I'd be astonished if they're not being cited by MAGA et al against you now.
Generally, if you treat people like children, like the CDC did, they won't respond by behaving like adults.
That trial has several issues. Everyone is patiently awaiting larger RCTs to further understand if Vitamin D does anything as a prophylactic. It's been shown to not be helpful in severe cases.
>It's been shown to not be helpful in severe cases.
That's a fairly strong assertion! Stronger than, "there is no evidence that is helpful in severe cases" for example.
You wouldn't happen to have a reference to back it up by any chance?
Anyway, I'm wondering why vitamin D is held to a higher standard than the polyclonal antibodies or Remdesivir. Where is the evidence that they're helpful in severe cases?
By the way, I'm not advocating for long-term, high-dose consumption (say over 2000 IU) consumption of vitamin D.
Deva Boone (devaboone) 's blog points out that this can lead to dangerously high calcium levels and has been covered on here several times recently [0][1]:
>Eventually we worked out what happened with Shannon: In 2013 she was diagnosed with mild osteopenia, a thinning of the bones that can be a precursor to osteoporosis. Her Vitamin D was low at the time, so her physician started her on over-the-counter Vitamin D supplementation at 5000 international units (IUs) daily. Five years later, she was still on this dose, and her blood Vitamin D level had risen to 79 ng/ml. This level is within what many labs call the normal range, between 30 and 100 ng/ml, but levels above 70 are almost always a result of high dose supplementation, and I have seen toxicity with levels between 70 and 100 ng/ml. (A better “normal range” based on what I have seen would probably be between 30 and 60.) Vitamin D builds up over time, so the longer someone is on a high dose, the more likely she is to develop toxicity. Shannon’s calcium levels began rising in the fall of 2018, when her severe symptoms developed.
What we should be doing now is mass-testing the at-risk population to identify those people with blood levels below 30 ng/ml and then do what is necessary to bring them up into the 30 to 40 ng/ml range. Ideally that could be done with sunlight, or food high in vitamin D - for example oily fish, liver, dried-shitake, ... But for the at risk demographic, in practice one would probably need moderately high-dose supplements, combined with monthly testing until they're above 30 ng/ml, followed by a switch to a lower-dose maintenance dose.
"Isn't there at least enough evidence at this point to recommend it for everyone with Covid?
No, not really. There is suggestive evidence from a small pilot study. There is likely an effect, though we can't yet say how large that effect is. A few doses of high-dose Vitamin D are probably not going to hurt, but there are harms to massive doses of Vitamin D - and if we give it to everyone indiscriminately we will see more of those. Also remember that younger patients were excluded from the assessment of mortality risk in the third study - because no one under 40 died in their study, despite the fact that most of them were deficient in Vitamin D."
It's complicated. There's a lot of nuance, and there's a very real likelihood that Vit D deficiency may just be a proxy for an unhealthy lifestyle.
>there's a very real likelihood that Vit D deficiency may just be a proxy for an unhealthy lifestyle
Seriously! You think that it might be possible that vitamin D deficiency doesn't exist at all and that people used to get rickets because of an unhealthy lifestyle. You're kidding right ...?
In case, it's not clear, I repeat:
>By the way, I'm not advocating for long-term, high-dose consumption (say over 2000 IU) consumption of vitamin D.
What I am advocating for is:
>What we should be doing now is mass-testing the at-risk population to identify those people with blood levels below 30 ng/ml and then do what is necessary to bring them up into the 30 to 40 ng/ml range. ...
Actually, I agree that the evidence for supplementation with vitamin D for general health, and improving all-cause mortality isn't there. That's why I wrote:
>Ideally that could be done with sunlight, or food high in vitamin D - for example oily fish, liver, dried-shitake, ...
But there's a sharp difference between the general health, then general respiratory disease, then COVID-19. As Deva Boone writes:
>But maybe Covid is different. Covid is a respiratory infection, and in meta-analyses severe Vitamin D deficiency does appear to increase the risk of respiratory infections. We also have a plausible mechanism through which Vitamin D could influence Covid. ...
OK, now you quote Deva Boone:
>No, not really. There is suggestive evidence from a small pilot study. There is likely an effect,
Her position is disputed here [0] in the HN comments by kovach
devaboone
>Here is what the article states: "Therefore, a multivariate logistic regression analysis was performed to adjust the model by possible confounding variables such as hypertension and type 2 diabetes mellitus for the probability of the admission to the Intensive Care Unit in patients with Calcifediol treatment vs Without Calcifediol treatment (odds ratio: 0.03 (95%CI: 0.003-0.25) (Table 3). The dependent variable considered was the need to be treated or not in ICU (dichotomous variable).) CI:-0.30 - 0.03 p:0.08." The statement is worded in a confusing way, but that is a non-significant p value. Of course we should not put too much into "statistical significance" but it is interesting to note.
kovach
>The only reason that p value is a bit high in that second multivariate analysis is because of the uncertainty of how much all the different risk factors like hypertension, T2DM, age >= 60 etc. affect ICU admission numbers.
But even with those variables controlled, the 95% confidence interval is 0.003-0.25, which at worst is a 4-fold reduction in ICU risk.
>
>We should also note that the Calcifediol treatment group had 14 patients ≥ 60 years old, and the non-Calcifediol group had 5. So the study looks even better with that in mind...
Another thing about this study, is that it's actually megadosing. IIRC, something like 100,000 IU on day 1, 50,000 IU on day 3.
That's probably safe in the short-term in a hospital setting as devaboone states. But further more, it's probably necessary in the context of keeping COVID-19 patients out of the ICU. If they have COVID-19 because they're low in vitamin-D, then a 5000 IU capsule is probably not going to be enough.
That's why I'm advocating to mass-test the at-risk population, and supplement until they're above 30 ng/ml.
First of all I'd like to preface this by saying that everything I write is with a light heart, and I'm not actually 'angry' or feeling any sort of ill will towards you. I know everything is weird now with COVID, and sometimes when we say stuff on the internet it might sound more aggressive than it is intended to. So, no matter what our different opinions are I love you dude, and if we were in person I'd buy you a beer.
That being said.
What do you think causes rickets? Where does Vitamin D come from? What used to cause outbreaks of rickets?
It is a completely plausible proxy for an unhealthy lifestyle. As in, not well or on the road to being not well (not judging those folks, but they're unhealthy and we want to help them get better because they're fellow humans and we love them).
So, I don't know, in summary, Vit D is complicated. That's all.
>Following PCR-confirmation of the President’s diagnosis, as a precautionary measure he received a single 8 gram dose of Regeneron’s polyclonal antibody cocktail. He completed the infusion without incident. In addition to the polyclonal antibodies, the President has been taking zinc, vitamin D, famotidine, melatonin and a daily aspirin.
If there's a game changing drug for COVID-19 in there I'd say it was vitamin D.
We covered the Spanish randomized open label, double-masked clinical trial of vitamin D just over a month ago. [1][2]
>“Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) p value X2 Fischer test p < 0.001.”
[0] https://twitter.com/PressSec/status/1312122950133272576
[1] https://www.sciencedirect.com/science/article/pii/S096007602...
[2] https://news.ycombinator.com/item?id=24366006