More Global COVID-19 Outbreaks, Vitamin D May Aid Prevention (Lecture 30)
Welcome to another MedCram covid-19 update. We will do some updates and also talk about preparation from a prevention standpoint. Here, we have our Johns Hopkins dashboard at 9,400 total confirmed cases; total deaths 3,200; total recovered 51,000. South Korea has the most confirmed outside of China, and we’re talking about aggressive testing in South Korea and Iran quickly shot up; we can see here. That’s a pretty large red dot.
欢迎来到MedCram covid-19的另一个更新。我们将进行一些更新，并从预防的角度讨论准备工作。在这里，我们有约翰霍普金斯大学（Johns Hopkins）仪表板，共有9,400例确诊病例；死亡总数3200;总共追回了51,000。在中国以外，韩国得到了最充分的证实，我们正在谈论在韩国进行的激进试验，而伊朗迅速飙升。我们可以在这里看到。那是一个很大的红点。
If we go to the Worldometer website. Active cases are actually on the decline probably because we are leaving an epidemic in China, but there are small epidemics relatively outside of China that are rapidly growing, and that’s why this is not continuing to go down. If we look at total cases, we can see that the inflection point has started to turn upwards.
Let’s look at the latest updates. A number of countries are reporting single digits cases, and in some cases, some deaths. Interestingly here, there are 586 new cases in Iran, but they’re also starting to show recoveries as well. We knew there would be recoveries, but we’re just not seeing a lot at this point.
We see that there are 10 new cases in Belgium; 9 of which came from northern Italy, and that seems to be a hot spot of spread throughout Europe. Remember that in Europe, there are free borders because of the European Union, so it’s not as if this is unregulated, constrained travel, at least as of a couple of weeks ago.
Four new cases in the United States; all of them being in California, which is a hot spot. There’s one in Los Angeles County; two who had recently traveled to countries that have had covid-19, and there’s one new case in Contra Costa County in Northern, California.
That’s like in case of coronavirus in Los Angeles; was reported by Fox 11 News that the patient is being taken care of at home in self-isolation and being treated on an outpatient basis.
The purpose of MedCram, what we’re doing here, is to talk about the data, the raw numbers, to talk about the medical aspects of this virus, and what we know is going to work. But of course there are things that are out there that are emerging that seem to have evidence but don’t quite fit with coronavirus at this point because we don’t have the data. At this point, let’s face it. We have no randomized controlled trials for coronavirus covid-19. They just haven’t been performed. So we’re forced to look at things that may work.
Vitamin D is one of those things we don’t have any randomized control trials that show that supplement with vitamin D works in covid-19, but we do have data about vitamin D specifically, and so I think it’s interesting to go over. I’ve gotten a lot of comments from people about vitamin D and the potential use for the coronavirus.
And even though this paper here is for the influenza virus, vitamin D is not actually having an effect on the virus itself as far as we know. It’s affecting the hosts, us, our bodies, our immune system, and how they deal with the virus. So potentially (vitamin D) might be something that is applicable to other viruses, and, in this case, the coronavirus.
And if you’ve thought about this, you’ll notice that there’s a lot of talk about what will happen in the summertime to the virus, and a lot of the talk has been about heat and humidity versus dryness, and I’m wondering if there’s another angle on this because vitamin D could be acknowledged as ” a seasonal stimulus” as defined by our Edgar. Hope Simpson. It will be crucial to prove it from a potentially easy and cheap prophylaxis or therapy support perspective. As far as influenza infections are concerned.
Now this paper talks about how, first of all, vitamin D is absorbed into the body, and how it is metabolized. The fact that it is a vitamin, you have to understand that we cannot generate or make vitamin D in our own body. But in fact, we need ultraviolet radiation from the sun to convert the inactive form to the active form.
I’ve always had a special place in my heart for vitamin D because that’s what I did in terms of my undergraduate research working in organic chemistry. And so you’ll know that vitamin D, for those of you studied, the structure is a lipid-soluble vitamin, and so it’s possible to overdose on vitamin D. So you have to be very careful with it because it is fat-soluble.
Now there’s a lot of talk about vitamin D in the immune system, and how it bolsters it, but something that’s also very interesting about vitamin D is it’s possible role in infections. And also it has a suppressive anti-inflammatory process. So, in other words, vitamin D can turn things on, and it can also turn things off. It’s not uni-modal, and that is something that could be very helpful, especially in the immune response that we see in covid-19.
Remember that it’s the immune system that is going to suppress the virus, which is good, but it’s also the immune system that could cause this storm of cytokines that puts your lungs into ARDS and could potentially kill.
So what we want is a smart immune system, an immune system that takes care of the virus but doesn’t put us into an inflammatory condition that could put us on a ventilator. So is vitamin D the answer? I have no financial relationships with any pharmaceutical companies or companies that make nutritional supplements in any way.
This study that was talked about here in the Harvard Gazette may be what we’re looking for here. It says a new global collaborative study has confirmed that vitamin D supplementation can help protect against acute respiratory infections. The study, the participant data meta-analysis. So a meta-analysis is simply a study that looks at a whole bunch of other studies, breaks down the components, and makes a super study out of it.
So they took actually 25 randomized controlled trials within an N number of 11,000 participants. That’s a pretty sizable number. This was published in the British medical journal. I will give you a link to that journal. We will actually look through that.
Most people understand that vitamin D is critical for bone and muscle health, says Carlos Camargo of the Department of Emergency Medicine at Massachusetts General Hospital. Our analysis has also found that it helps the body fight acute respiratory infection, which is responsible for millions of deaths globally each year. Remember this article was published before coronavirus.
Several observational studies with track participants over time without assessing a specific treatment have associated low vitamin D levels with greater susceptibility to acute respiratory infections. I don’t have to tell you that living in high latitudes, especially in the wintertime, exposes you to the least amount of sunlight. If you have the least amount of sunlight, you would conclude appropriately that your vitamin D levels are generally going to be on the lower side.
Well, it’s possible that the seasonal variation in the virus may still have something to do with the survival of the virus outside the body, but it may have more than we think to do with the survival of the virus inside the body. It is a postulate, but it’s interesting. The meta-analysis of these trials which aggregate data from several studies that may have different designs or participant qualifications also had conflicting results.
And this really has been the issue for some period of time. Some studies show that there is a connection that makes vitamin D look good in terms of preventing infections; others, not so good. So to resolve these discrepancies, this research team out of Queen Mary University of London conducted an individual participant data meta-analysis.
What does that mean? They grouped all of these studies together, and then they stripped it down to each particular individual, and that is very powerful, producing what could be considered a higher-resolution analysis of the data from all the studies.
The investigators found that daily or weekly supplementation had the greatest benefit for individuals. Number one. There was a benefit. And number two: it was the turtle, not the hair. What I mean by that is it was the daily supplementation, not the huge doses of vitamin D, if you got sick.
This makes sense to people who have the lowest levels are going to have the best effect from supplementation, and it cut their risk of respiratory infection in half. That is a significant number and could reduce the R-naught or the replication number in viruses, and it may be the reason why we see these viruses disappear in the summer. I say MAY; don’t have proof of that yet, but it’s interesting.
All participants experienced some beneficial effects from REGULAR vitamin D supplementation. Administering high doses of vitamin D did not produce significant benefits. This study was not funded by some nutritional company, but was funded in fact by the British National Institute of Health Research.
So let’s actually go to that study. It’s open access, and I will put the link in the description below. This is from the British Medical Journal; that’s a very prestigious publication. In the conclusion, vitamin D supplementation was safe, and it protected against acute respiratory tract infection overal. Patients who were very vitamin D deficient, and those not receiving bolus dose (a single dose of big quantity), have experienced the most benefit.
So, if you go down to the raw data, they had to come up with cut-off points. And for those of you who don’t know how to read studies, let me show you here a little bit. What they’re looking at is how many respiratory tract infections they receive. So “one step individual participant data meta-analysis, proportion of participants experiencing at least one acute respiratory tract infection.”
First thing to do is to look at the very top one, and that’s overall. How many trials? 25. Proportion with greater than 1 acute respiratory tract infection, and proportion with greater than 1 acute respiratory tract infection in the intervention group, and you can see that there was a difference. And what was the difference? The adjusted odds ratios where you want to look.
There’s another way of looking at two, looking at P values, to see if there’s a difference between these two groups. Those in the control group, those in the intervention group, and any p-value of less than .05 is considered to be statistically significant. So you can see here that a bolus dose of greater than 30,000 international units given had a p-value of .67, that’s greater than .05. Therefore, it is not statistically significant. In other words, a bolus dose is not going to be helpful. If the toast wasn’t given, you can see that was very statistically significant.
So the question is how much should I take on a daily dose? Well, here it is: daily dose equivalent. If it was less than 20 micrograms, highly statistically significant; if it was 20-50, still statistically significant. However, if you took more than 50 micrograms, there was no difference between that group, indicating that a modest dose of vitamin D every single day would be the best.
Here’s more research in the study, showing all of the different individual studies and the proportion with greater than 1 acute respiratory tract infection. You can see here where they lined up relative to number 1. Number 1 being no difference. If it was less than number 1 with a 95% confidence interval less than 1, then you could say that that was statistically significant. And it was weighted based on the number of patients in that study. Finally, we come to the overall, which is here at the bottom, P-value of .001. You can see that it lands less than 1.
If you scroll down to the discussion, it says vitamin D supplementation reduces the risk of experiencing at least one acute respiratory tract infection, and it talks about the grade of the data, which was very good. The question though is why would a bolus dose of vitamin D be ineffective, and they talk about how the wide fluctuations of circulating 25 hydroxy vitamin D concentrations, which is the starting material for the active form in the body, could deregulate activity of enzymes responsible for the synthesis and degradation of the active vitamin D metabolites, which is 125 dihydroxy vitamin D. So my recommendation based on this data would be to take a small supplement of vitamin D every day. And again, we’ll put the links to these articles in the description below.