One has to be wary, but while I think we should temper our enthusiasm, some of the news is definitely good. For example, the Moderna vaccine being able to elicit antibodies without causing significant adverse reactions is encouraging. They're using a novel technique for developing vaccines, so safety profile in particularly is a huge concern. It was only like 8 patients though, and nobody has access to the actual study so we don't know the details, hence the advice to temper enthusiasm. As for the Oxford vaccine, I believe that while it wasn't very effective in preventing the infection, it does appear to reduce the severity of infections in the monkeys that were vaccinated. In that sense it may be a bit like the flu vaccine, where it's only 25% effective in preventing the flu in some years, but still very effective in reducing the severity of disease. Again, the actual study is unpublished, so we don't know the details.
Now, hot off the press, here's the first peer-reviewed study on a vaccine under development published just yesterday on The Lancet. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext These are phase 1 results from a vaccine under development in China. I've just read through it, here's my first take. I tried to keep it relatively brief but still comprehensive, and I bolded the really important parts for those who just want a cliff notes version. Q: What is this vaccine? A: It's basically a genetically modified Adenovirus, another family of viruses that causes the common cold, similar to Coronavirus (well, before coronaviruses started killing people anyway). It's modified to make it 1) unable to reproduce and 2) contains SARS-CoV-2's (the virus that causes COVID, but for simplicity's sake I'm gonna use COVID and SARS-CoV-2 interchangeably) characteristic spike protein. It's the same strain (Adenovirus 5) used in research to create an Ebola vaccine. Q: What was the purpose of this study? A: As a phase 1 study of a vaccine, it's primarily to study the safety profile. Secondarily it evaluated the subjects' immune response toward the vaccine. Q: How was the study conducted? A: I'll spare you guys the details, but basically the subjects were given a battery of tests (blood test for antibodies, pharyngeal/anal swabs, sputum test, and chest CT) to make sure they don't have COVID before the vaccination. They then tested out 3 different doses (low, medium, high) of this vaccine on 108 people (36 in each group). The subjects were monitored for symptoms and their blood was tested for antibodies (made by B-cells) and T-cells specific to COVID at regular intervals (7 days, 14 days, 28 days). They then mixed the blood samples with COVID samples to see if the vaccinated subjects' serum can kill COVID. Q: What were the results? A: 1) There were no significant adverse reactions, but there WAS a high prevalence of side effects. About half of the subjects developed fevers, for example, and 40% with fatigue. There appears to be a dose-dependence to side effects (i.e. higher dose vaccine = more side effects). Now, the Chinese definition of fever is more stringent than ours. Here in the states we consider 38C as a fever whereas in China 37C is considered a fever and 38.5C is considered a "severe" fever. 2) All 3 doses elicited a significant immune response by 28 days post-vaccination. 94-100% of the subjects have developed antibodies against the receptor binding portions of the spike protein (i.e. prevents COVID binding to human cells). At 14 days it was 44-61%. This also appears to be dose dependent. 75% of the high-dose group also developed neutralizing antibodies against COVID. I'm not too sure what it means by that, but I think it means antibodies that would kill the virus. There was also a significant T-cell response, by both CD4 (helper) and CD8 (killer) T-cells. Q: What are some of the limitations to the study? A: 1) Developing an immune response does not mean a person is immune to the virus. Exactly what the immune response do for us, i.e. whether it can prevent infections and/or reduce severity of disease will be studied in phase 2. However, it's encouraging that this study demonstrated not only an antibody (i.e. B-cell mediated) response, but also a robust T-cell mediated response. This is important because prior studies on SARS and MERS showed that antibody titers diminish rapidly after recovery, but T-cells confer more long-lasting immunity. This study also had an interesting nugget buried in the Discussion section. Apparently, in animal studies, only 1/8 ferrets caught COVID after an exposure 21 days after vaccination, whereas 7/8 ferrets who were not vaccinated caught COVID. 2) The inclusion criteria for test subjects are fairly restrictive, which is the standard procedure for a phase 1 study but nevertheless needs to be considered. For example, only 1% of the subjects had pre-existing conditions, and the age range is 18-60. 3) There was a high prevalence of Adenovirus antibodies in the study subjects, and many with Adenovirus antibodies did not develop neutralizing antibodies against COVID. They did, however, still develop antibodies against the COVID spike protein, which may be sufficient, but we won't know until phase 2/3 trials. As mentioned before, Adenovirus is a common family of viruses that cause colds so this is a potential issue. 4) Older age appears to be associated with a less robust immune response, I'll comment more on this on the next point... 5) I foresee the side effect profile as a major issue for adoption in the U.S. I can't tell you how many times I've had a patient tell me he won't take the flu vaccine because it gave him the flu. That's impossible, because the flu shot does not contain live virus. It can, however, elicit an immune response that gives you fever, headaches, and muscle aches much like this vaccine. This vaccine contains actual live Adenovirus (although it can't replicate, so the infection is assuredly self-limited and non-contagious, and this strain, Ad5, is well known to be benign anyway), so the prevalence and magnitude of side effects will be even higher. This means that for many people, getting this vaccine may not be that much better than getting COVID in terms of how their body will feel. This is an issue because this vaccine, as is the case with most vaccines, appears to be less effective for the elderly, the highest risk group for dying of COVID. The elderly therefore cannot rely on just getting the vaccine, they'll have to rely on the rest of the population developing herd immunity. If the low-risk population refuse to take the vaccine, which is not contagious, then they're liable to catch the actual disease, which IS contagious and can be passed on to the high-risk population.
Thank you for the breakdown. You've been an awesome source of information on this forum and we are lucky to have you posting here.
I was supposed to begin my vacation in Hawaii today, but since that's been cancelled I guess I'm just sitting at home reading Covid studies The design and method of this study are pretty typical, as you'd expect from a double-blind, randomized, placebo-controlled trial, so I won't comment too much on it. Some of the results were published already, but the publication of the full study obviously gives a lot more details. The key takeaways for me on first pass are: 1) The decrease in time to recovery was published before, but now we know that it's statistically significant. 2) The decrease in mortality was published before as well, but now we know that it's NOT statistically significant. With that said, there's a strong trend toward improvement in mortality, especially for the less severe cases, which leads to my 3rd point... 3) This medication appears to be most effective in the less severe cases, as previously expected. If you need non-invasive ventilation or high-flow oxygen or more (i.e. invasive ventilation or ECMO), then it doesn't appear to be very useful at all. I would've really, really liked for the trial to have continued another week or so, and for the design to have included a comparison between groups of different disease severity from the start. That IMO could've proven a mortality benefit which is the golden grille of any intervention. As it stands now, it might be unethical to conduct another study comparing against placebo given the benefits shown in this study, so future interventions will likely be comparing with Remdesivir rather than placebo.
Friend of mine sent me a link to an investigation using Remdesivir with an ant-inflammatory to control immune overreaction. Researchers try combining remdesivir with a second drug to deliver a "one-two punch" to virus - CBS News Best to not get on a plane now.
If a vaccine can be proven to be safe (no unintended serious consequences) but yet has the potential to make me sick with a self-limiting infection, I would still take it over the actual SARS-CoV-2 which may not kill me, but could do everything from damage my lungs to ruin my kidneys and basically cut my life short.....but that is just one man's opinion.
Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis
We Absolutely need interventions before people get very sick. By the time people experience shortness of breath and go to the emergency room, it is very late in the game.
Not everything is insider trading. CEOs, CFOs, CMOs and other top Execs usually have a predefined sale plan under 10b5-1 rules. This is also stated in the article - “Moderna said the sales were executed under 10b5-1 trading plans that were established in advance. "These transactions are 10b5-1 executing automatically pursuant to these trading plans," the company said. Although the fortuitous timing of the transactions may raise eyebrows, Charles Whitehead, professor at Cornell Law School, said the stock sales did not appear to raise any legal red flags.“ Moderna execs dumped nearly $30 million of stock after coronavirus vaccine news - CNN
When it's pathological, logic doesn't come into play. To his base, lies are of no consequence...they simply choose not to care.
The problem isn’t insider trading. It is the announcement before they sold. Pre-Planned or not. Because they know their plans and pumped their drug investigation right before the preplanned sales. Nothing fortuitous about that. To the contrary, they should have held the announcement. It is called pump and dump.
But why would/should they? It’s not like there was a leak of the results (like remdesivir) or they disclosed false/misleading news that artificially pumped the stock. That the general public and investors overreacted to their study results is debate worthy.
Interesting study that has been submitted for peer review, but has not been reviewed so. However, as close in on being a Senior and someone who is on an a low dose ACE inhibitor + calcium channel blocker I find this result intriguing. Not sure if I quoted it, but the study did conclude there was no impact on the death rate between those taking ACE inhibitors vs not once they did get to the hospital. Seniors with COVID-19 taking ACE inhibitors have lower hospitalization risk
I guess the one element of this that I would like to see studied, if this drug is safe for Lupus and Rheumatoid arthritis, but not for treating Covid-19, what the the reaction/interaction that makes it not safe? Looking at it the other way, should Lupus patients be on this stuff if it is that dangerous?? U.S. hospitals slash use of drug championed by Trump as coronavirus treatment
