SARS-CoVID-2/ CoVID-19/ CoronaVirus: Information Only from Well Informed Members

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Do any of you have insights, information or opinions on what the Moderna mRNA-1273 Vaccine Phase 1 Trial Results mean aside from the fact that it is good news that they seemed safe at all dosage levels and that the lowest dosage level elicited neutralizing antibodies (an immune response) of the magnitude caused by natural infection. (I think I have that information right).

The report I read said that dosages of 25mcg, 100mcg and 250mcg were used on 45 people, with 15 people in each dosage group.

I would love to hear what you guys feel these reports actually mean rather than the media hype on the subject.

Thank you.
 
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A long time ago the way a vaccine was made was to take some microbe or virus and kill it with heat or exposing it to formaldehyde and then inject the killed virus or bacterium into a person. The person would then develop an antibody response without getting sick.

Later, vaccines were made by taking just one or a few of the exposed proteins of a virus and using them to make a vaccine. These are expensive to produce because creating a recombinant protein on an industrial scale is a very complex process and there are all sorts of pitfalls along the way. Obviously since one or a few proteins comprise only a part of the virus it can't make you sick (unless the actual immune response to it produces a bad reaction). Nearly every vaccine you would take now is made that way. One issue is that it takes a long time to scale up for production.

The idea behind an mRNA vaccine is you inject the mRNA that encodes a viral protein. If you package it exactly the right way (and this is the trick) it will get incorporated into cells in the general vicinity of the site of injection. Those cells will start making the viral protein and putting it onto the cell surface. For SARS viruses you would probably choose the S-protein. The immune system sees these foreign proteins on native cells and says WTF!!!! What is that????? And starts to make antibodies against it. That response is stored in so-called "memory T-cells" and later on in the future if a person is infected with a SARS virus a big antibody response should stop the infection from spreading or becoming significant.

The advantage is that it is a lot easier to scale up RNA production on an industrial scale. The secret sauce is packaging the mRNA in a way that some of the normal cells will take it up and use it to make the viral protein it encodes with a so-called "signal sequence" so that it will appear on the cell surface. The mRNA and the protein it encodes has to stay around long enough for the immune system to see it, respond to it, and then remember it.

The fact that this seems to be working is a big advance in my opinion.
 
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More about neutralizing human monoclonal antibodies

https://www.nature.com/articles/s41586-020-2349-y

What is cool about THESE is they were derived from a patient who recovered from SARS in 2003 but they work against SARS-COV-2. Also the authors are finding several which means that they will be able to create a therapeutic cocktail of these, and also even if the virus mutates a lot in the future the antibodies should continue to work.

What is the barrier to mass producing a therapy like this? Does the SarsCov1 survivor repeatedly have to donate via blood? Or is it so expensive that it will require massive capital investments and will thereafter be available only to the rich?
 
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What is the barrier to mass producing a therapy like this? Does the SarsCov1 survivor repeatedly have to donate via blood? Or is it so expensive that it will require massive capital investments and will thereafter be available only to the rich?

The antibody from the original SARS patient has been cloned so it is not necessary to ever take blood from him/her again. It is even possible that the people creating this recmbinant human monoclonal antibody have no idea who the original donor is. I think the main idea is that a cocktail of monoclonal antibodies would work better and they are still needing to develop a few more of these to make sure they have the most effective product. (Normally a human immune system will make many different antibodies against a virus, a so-called polyclonal response).l Once they are satisfied with their mixture they need to make enough of the stuff to go through clinical trials. I don't think it will take a massive capital investment because I suspect this company has it in place or they could readily get an agreement with some other company that does this routinely (production on a large scale).

So the next step, probably not to far down the road, are Phase 1 and Phase 2 clinical trials in hospitalized patients. Remember these antibody cocktails need to be given by intravenous infusion. And some of the details on the best way to use them will need to be worked out. But this is a very positive development.
 
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The idea would be to infuse them into people who are infected to prevent the virus from spreading to adjacent cells, giving your own immune system a big advantage in its battle with the virus, preventing disease progression and speeding recovery and reducing hospital time. Could you use them to prevent infection? Maybe, it depends on how long the infused antibodies persist in your body, indeed they can be engineered to persist longer. However my initial thought is that strategy is almost certainly cost prohibitive. Monoclonal antibody therapies for other conditions (like rheumatoid arthritis) cost thousands of USD/month. But I could be wrong about that.

Most likely we still need to develop vaccines.

The infused antibodies would not "teach" your body how to make its own antibodies or increase their production. They would buy time until your own immune response maximally kicks in. They are like reinforcements. They act the same way as a blood transfusion from someone who recovered from the virus (maybe a bit better since these engineered ones would be optimized and can be given in a higher dose).
 
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Coronavirus vaccine trials have their first results — but their promise is still unclear
Scientists urge caution over hints of success emerging from small human and animal studies.
https://www.nature.com/articles/d41586-020-01092-3

You may notice that Moderna stock price dropped ~10% today (jumped ~20% yesterday) as some researchers expressed concerns about the data from their press release. Also Moderna people including CEO are selling more stocks. So be more cautious and patient about the results of the vaccine - it takes time to obtain the results and evaluate.
As BioCentury summarized, >100 vaccines are under development and ~10 enters clinical trials. I am pretty positive that we will have good vaccines. The questions remain though, like how soon they can be distributed, who can get access first and how much one has to pay.
https://www.biocentury.com/article/305154/a-guide-to-covid-19-vaccine-modalities-in-the-clinic
https://www.biocentury.com/article/305208/a-guide-to-covid-19-preclinical-vaccine-modalities
 
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Rain is right, the proof is in the pudding and we scientists tend to be a cautious lot.

One reason I am confident about a vaccine is the number of different strategies that are being pursued to develop one. People are using old tried and true methods (like Sanofi) as well as a variety of innovative methods. The mRNA method described above is one example but there are a bunch of others.

Another relatively new approach is to incorporate the gene encoding the viral S protein into some human cells, and one way to do that is using ANOTHER virus called an adenovirus that has been heavily engineered to function as a "vector". As with the mRNA method, you inject the adenovirus vector into the skin, or sniff it up your nose, and human cells that are "transfected" bythe vector start to make the SARS-COV2 S-protein and put it on the surface. The immune system sees it, and makes antibodies etc.etc. I actually think that approach is more likely to give a sustained protection and a bunch of groups around the world are pursuing it. A big advantage is very rapid scale up for industrial production. Downside is regulatory agencies will be ESPECIALLY vigilant about safety issues if adenovirus vectors are used.
 
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This is a study from Korea documenting spread of Covid-19 from instructors to students in Latin dance fitness classes.

https://wwwnc.cdc.gov/eid/article/26/8/20-0633_article

Well that was interesting... particularly this:
Of note, instructor C taught Pilates and yoga for classes of 7–8 students in the same facility at the same time as instructor B, but none of her students tested positive for the virus. We hypothesize that the lower intensity of Pilates and yoga did not cause the same transmission effects as those of the more intense fitness dance classes.
Instructor C had 25 students, in total, and none of them caught the virus. I wonder whether those classes were twice a week as the dance classes were (seems like it, since article said "at the same time").

So if I'm at a table tennis club, with just my coach and have him block or not exert himself much, maybe the risk is much lower (for me). ;-)

Edited to add:

I'm sure the researchers would have noted this, but I wonder whether Instructor C wore a mask, or whether any of the instructors or students did.
 
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I think the space was fairly small also for some of the dance classes. It definitely is consistent with the fairly intuitive idea that if you are exhaling hard because of aerobic exercise you would eject more virus if you were infected. Again, though, time and distance and luck. Three of the factors.
 
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Hey guys, first of all I considere this a question but I need to tell a backstory so it makes sense. Carl, if you don't considere this relevant or something like that feel free to delete my post.

So I have been at my cousins birthday last sunday and there was a man there who came home from Germany (where he works). He didn't shake hands or touch anyone but he was in a same room with my parents for about an hour (I was in my cousins room).

At monday that man recived a call that a man at the place that he works at has covid 19, so he payed himself a test and results showed that he has the virus tuesday morning. Everyone that was neer him including my family recived a call to stay at home and wait for further intruction.

First they have tested 2 man that have been traveling with him for 12 hours and his wife and children, and everybody was negative on corona. Me and my perents got tested this morning and are also negative (test sucks by the way, ih hurts). The man that has corona doesn't have any high temperature, any problems and he feels normal.

My question is is it possible that he has the virus but doesn't spread it, or was he over it at the time he came in Croatia and wasn't contagious anymore. I'm very interested especially because his wife was negative and they hev huged and kissed and stuff so he can't be contagious. What do you more informed guys think?
 
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The good news is you were tested carefully. To be honest, the swab needs to be pushed all the way to the back of your nose to get to where the virus is most likely to be, and that hurts. A doctor colleague of mine has told me he truly hates it, and he's had it done several times now. The way the swab is used is probably a big reason why some false negatives occur.

As to your question, there is no clear answer. Maybe his test was a false positive, or more likely his immune system effectively killed the virus so that he wasn't spreading it anymore when you met him.

It is good you are ok! And clearly Croatia us doing a better job of testing and tracking than the US. You got your test result the same day.
 
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The good news is you were tested carefully. To be honest, the swab needs to be pushed all the way to the back of your nose to get to where the virus is most likely to be, and that hurts. A doctor colleague of mine has told me he truly hates it, and he's had it done several times now. The way the swab is used is probably a big reason why some false negatives occur.

As to your question, there is no clear answer. Maybe his test was a false positive, or more likely his immune system effectively killed the virus so that he wasn't spreading it anymore when you met him.

It is good you are ok! And clearly Croatia us doing a better job of testing and tracking than the US. You got your test result the same day.

Thank you Baal! This was the second case in my, idk how it's called in english, like a province or a shire, but I am suprised by the fast results also given that the man was at a big party with 50 people on monday, so they have all been tested, we might just be lucky to get the results so fast.

I'm just sad I wll have to do the test again troughout next week for security reasons, but what must be done it must be done. I'm happy that I don't have it tho :)
 
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Marko, just remember that large groups of people indoors is a bad idea, especially if there are many people you dont know. We're not through this yet

By the way, I saw a little bit of your country last summer, took a ferry over from Italy to Dubrovnik. I really liked it!
 
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My question is is it possible that he has the virus but doesn't spread it, or was he over it at the time he came in Croatia and wasn't contagious anymore.

Yes, definitely possible. As Baal wrote, his test may have been a false positive but more likely he just wasn't very contagious when you met him. Viral shedding and transmissibility vary throughout the course of the disease. Current research suggests patients tend to be most contagious just before and during the onset of symptoms. That's often when the concentration of infective viral particles is highest in the upper respiratory tract where it can easily be breathed/coughed/sneezed out. At other times most people are probably less contagious, or even not contagious at all, even though they might still test positive for the virus.
 
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Marko, just remember that large groups of people indoors is a bad idea, especially if there are many people you dont know. We're not through this yet

By the way, I saw a little bit of your country last summer, took a ferry over from Italy to Dubrovnik. I really liked it!

Yes, I know, that was the first gethering I went at since this started, just because that is my closest cousin, and we didn't know that man will be there, I do know him tho, but we didn't know he was home.

And yes Croatia seaside is georgeus, but the goverment is trying to save the tourist season and they are opening the borders which is very bad idea, but tourism is Croatias main income so I kind of understand it. The numbers of infected people in Croatia might go up due to that so we should be carefull.
 
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Firstly, thanks Baal, Dr evil and rain for taking the time to answer questions.
I am curios as to how the logistics of rolling out a vaccine work:
1. If a hypothetical vaccine would pass Phase 2/3 would other researchers stop developing their vaccines?
2. does passing phase 3 which needs only thousands of doses mean that mass production is assured( as in is there a gap when passing phase 3 and mass production or does phase 3 occur simultaneously with creating mass production capability )?
3.Would the information of how to make the vaccine become open source so that everyone could attempt to make a generic version or would the formula stay proprietary?
 
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