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

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Thoughts on the vaccine questions described in this article?

https://www.theguardian.com/world/2020/may/22/why-we-might-not-get-a-coronavirus-vaccine

To take one of several priceless quotes from a guy named Larry Brilliant "If and when we have a vaccine, what you get is not rainbows and unicorns,” says Larry Brilliant, CEO of Pandefense Advisory, who led the WHO’s smallpox eradication programme. “If we are forced to choose a vaccine that gives only one year of protection, then we are doomed to have Covid become endemic, an infection that is always with us.”
 
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Somebody asked about an article in the Guardian on why we might not get a vaccine. (They seem to have deleted their post though, but I already wrote the answer).

I like the Guardian. I think in general this newspaper article is starting from the most pessimistic possible position and then examining if there are ways to support it, and this is what emerged. In general I dont think that position is very convincing.

If you look a bit closer at one of the papers cited in the article ( not yet peer reviewed) you see this:

"Despite low plasma titers, antibodies to distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as few ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 without hospitalization do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested."

A higher titre (a fancy word for concentration) of antibodies, all other things being equal, is better. But that should increase rapidly if someone is exposed again to the same antigen unless they are severely immunocompromised. That is how the immune system works.

Yes, it is possible that someone might need to get a booster every few years. (Obviously that could be a bigger issue in developing countries, which seems to be the background that the guy who us quoted brings to the table). That is not the same as saying that a vaccine will fail. And no vaccine is ever 100% effective, but even partial effectiveness would probably keep people from dying.

As for common colds, the article states that 1/4 of common colds are caused by other coronaviruses but people continue to get colds. That does not mean anyone is ever re-infected by the SAME coronavirus (of which there are several).

Even with a vaccine for many reasons not everyone will take it. So the virus may well remain endemic in some areas. I will certainly take it.

Lastly, this virus is an ideal candidate for a vaccine. Its S-protein is very structurally constrained. It dosen't hide the way HIV does. Sera in recovered patients is therapeutically effective.
 
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What would be the positives and negatives of wearing a cycling mask while playing table tennis?

Depends in part on what kind of mask.

I'll start with an N-95 or KN-95 (if it's made in China). This is what healthcare workers ideally wear around patients. It filters out 95% of particles above a certain size and fits VERY tightly around your face. These are not generally available except for healthcare workers in the US (but you can buy them from some Chinese websites). They are really uncomfortable to wear for any length of time (they are hot, they tend to chafe your skin, etc.). They do tend to constrain breathing a little, and I don't think there is anyway you would be able to have fun playing TT in one, even if you can get it. I have worn them in the lab doing surgeries on animals and I can't wait to take them off. They would confer the highest level of protection though.

Other kinds of masks might be more comfortable to wear. They would also confer less protection to the wearer, but would tend to protect other people if the wearer is infected. It turns out that the virus particles are suspended in larger droplets when they first leave your nose or mouth, they get into the air and stay there for variable lengths of time, during which the droplets tend to evaporate and the particles become smaller. So you can inhale them around the sides of a looser fitting mask, but your mask tends to stop a lot of them ones that leave your nose or mouth from getting into the general atmosphere. From the wearer protection point of view, definitely better than nothing, but how much better depends on a lot of things (material, how it fits, etc.) You can certainly breathe well enough through most of them (based on experience I have had on a road bike riding at 95% of my maximum heart rate). Masks tend to keep you from touching your face. The best ones have a wire piece that you can bend around the bridge of your nose to improve the fit.

Things I can't answer (because I haven't tried it) include following considerations:

  • How annoying it would be to wear a mask in TT, where you are moving around on your feet very quickly and sometimes abruptly. On a road bike your head doesn't move a lot. The wind doesn't seem to move it though. How distracting would it be in TT?
  • Would the straps pulling behind your ears start to hurt?
  • Would it chafe you skin? Would it be too hot?
  • How well would it work if it's soaked with sweat and would it start to impeded your breathing at that point (probably would, on a road bike the wind tends to keep that from happening).
 
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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?

I'll take these in order:

1. No, other groups and companies would continue, especially if they were very far along in the development path, especially in a disease like this. The analogy is drug development, let's take statin drugs as an example. After the first one one came out, other companies continued to develop their own versions and now many are approved for use, even though they more or less all do the same thing (with some slight differences in adverse effects etc.). Patients with high cholesterol in the world is a huge market, and as a class these drugs are all reasonably effective. This pattern repeats for many different drug classes, and the more widespread the disease the more you see it (see for example gliflozin drugs for diabetes, there are no fewer than seven that have been approved in various countries in the world, four in the US). This would be the same for Covid-19 I am quite sure.

2. My best guess is that it would depend on the nature of the vaccine and the the group that developed it. It is hard to know about supply chains, manufacturing, etc. if you are not in that exact business, and I am not. Companies that have a long record of making vaccines would probably have an advantage, and it is likely that a vaccine developed by a smaller group would require a consortium with other companies for mass production. I think a DNA or RNA vaccine would be easier to scale up just because of the nature of the chemistry.

3. No, it would almost certainly remain proprietary. Even public and private non-profit organizations (like the university where I work) take very good care of their intellectual property rights, especially when there is a chance to make billions of dollars. The Division of Research at my university has frequent presentations on what we should do if we discover something that is worth patenting. How hard it would be to reverse engineer an effective vaccine (something they would try to do in China for sure) would depend a lot on what it is and how it is formulated to be most effective. This would probably be relatively easy to do for a DNA or RNA vaccine (which is a very new technology, but which is being pursued in a bunch of places). It might be a bit harder for more traditional vaccines, and it might also depend on what little tricks they are using to enhance the immune response to the antigen (is there a proprietary adjuvant, are they using a microneedle array, etc. etc.). In other words, finding the antigen is not the hard part.
 
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Thoughts on the vaccine questions described in this article?

https://www.theguardian.com/world/2020/may/22/why-we-might-not-get-a-coronavirus-vaccine

To take one of several priceless quotes from a guy named Larry Brilliant "If and when we have a vaccine, what you get is not rainbows and unicorns,” says Larry Brilliant, CEO of Pandefense Advisory, who led the WHO’s smallpox eradication programme. “If we are forced to choose a vaccine that gives only one year of protection, then we are doomed to have Covid become endemic, an infection that is always with us.”

I have Undelted Brs's post. I did not read the question before the link as a question. But....I see it is. And, Baal, since you answered, I have put it back so people have the link to the article.
 
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The first COVID-19 vaccine to reach phase 1 clinical trial has been found to be safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in humans, according to an Article published in The Lancet. The open-label trial in 108 healthy adults demonstrates promising results after 28 days—the final results will be evaluated in six months. Further trials are needed to tell whether the immune response it elicits effectively protects against SARS-CoV-2 infection.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext

I think the result of phase I vaccine trial from China (CanSino) is quite encouraging as it induced the production of neutralizing antibodies (~50% in low/middle dose groups and 75% in high dose group) as well as T-cell responses. From Chinese news, ~500 subjects entered phase II (placebo, low/middle dose) and preliminary result will be expected soon.

As I posted earlier the summary by BioCentury, more than 100 vaccines were under development and 10 entered clinical trials. I don't think the world should put all the eggs in one basket. Even 2-3 vaccines really work out (like Moderna's mRNA vaccine, CanSino's adenovirus based vaccine, SinoVac's inactivated virus vaccine), research on other vaccines should not stop and will not stop due to scientific, industrial, political reasons.
SinoVac said they can make 100-200 million doses a year, and I don't recall other companies said their vaccines could be produced more than 100 million doses a year. So there is still a huge demand. That's why I mentioned it will become an issue who (which country) can get access the vaccine first. CanSino's vaccine is collaborating with Canada for clinical trial there; it sounds like normal market relationship. France's Sanofi were criticized a few days ago when they said something like they will prioritize US when they develop vaccine because they received funding from US; later they apologized. With limited supplies of vaccines, I feel like a "fight" for vaccines, from IP, to massive manufacture, to pricing, is not avoidable. And we do need regional and global collaborations, to make the vaccines affordable and accessible to the world.
 
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The first COVID-19 vaccine to reach phase 1 clinical trial has been found to be safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in humans, according to an Article published in The Lancet. The open-label trial in 108 healthy adults demonstrates promising results after 28 days—the final results will be evaluated in six months. Further trials are needed to tell whether the immune response it elicits effectively protects against SARS-CoV-2 infection.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext

I think the result of phase I vaccine trial from China (CanSino) is quite encouraging as it induced the production of neutralizing antibodies (~50% in low/middle dose groups and 75% in high dose group) as well as T-cell responses. From Chinese news, ~500 subjects entered phase II (placebo, low/middle dose) and preliminary result will be expected soon.

Was reading through the paper linked above and noticed the following regarding side effects of the vaccine:
Between 42% and 56% of the participants reported a fever. Between 6 and 17% reported a Grade 3 fever. I found one reference to a grade 3 fever definition which was a temperature of 104 or higher for less than 24 hours. Is that the same definition as used in the paper???? (The Discussion section in the paper apparently refers to it as severe fever, stating these reactions were, "transient and self-limiting." I'm no doc, but a 104 plus temperature sounds frightening to me, especially in older folks. (The paper said 60 was the upper age range of participants, but doesn't list the age of those who experienced a Grade 3 fever.) Wouldn't that kind of reaction be a concern for older patients getting this kind of vaccination? (I realize even a vaccine only younger people took, would still reduce the likelihood of infections for the non-vaccinated.)



There was this in the Discussion section:
We noticed a higher reactogenicity profile of the high dose at 1·5 × 1011 viral particles, presenting as severe fever, fatigue, muscle pain, or joint pain, which might be associated with viraemia caused by Ad5 vector infection. However, the severe adverse reactions were transient and self-limiting. Additionally, no abnormal changes in laboratory measurements were clinically significant or considered to be related to the vaccine. The profile of adverse events reported in this trial is similar to that of another Ad5 vector-based Ebola vaccine expressing glycoprotein.
 
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In this Lancet paper, it said, "Nine participants (two [6%] in the low dose group, two [6%] in the middle dose group, and five [14%] in the high dose group) had an episode of severe fever (grade 3) with axillary temperature greater than 38·5°C."
In the supplementary results, it summarized that the grade 3 fever occurred on the same day or 1 day after vaccination and lasted 24-48h. 2 people from high dose group took antipyretic medicine and others did not take medicine.
https://www.thelancet.com/cms/10.10...d2f4d28a-f892-449e-bf56-b0e92c72609a/mmc1.pdf

I think 38.5C/101.3F is not as scary as 40C/104F and it went away quickly :) But you're right, vaccine will cause adverse effects and we have to be careful to test the safety (phase I) first. In this phase I trial, all subjects are below 60. In the ongoing phase II trial, some subjects are over 60, the eldest being 84. Let's see what results will be.


Was reading through the paper linked above and noticed the following regarding side effects of the vaccine:
Between 42% and 56% of the participants reported a fever. Between 6 and 17% reported a Grade 3 fever. I found one reference to a grade 3 fever definition which was a temperature of 104 or higher for less than 24 hours. Is that the same definition as used in the paper???? (The Discussion section in the paper apparently refers to it as severe fever, stating these reactions were, "transient and self-limiting." I'm no doc, but a 104 plus temperature sounds frightening to me, especially in older folks. (The paper said 60 was the upper age range of participants, but doesn't list the age of those who experienced a Grade 3 fever.) Wouldn't that kind of reaction be a concern for older patients getting this kind of vaccination? (I realize even a vaccine only younger people took, would still reduce the likelihood of infections for the non-vaccinated.)



There was this in the Discussion section:
 
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I think 38.5C/101.3F is not as scary as 40C/104F and it went away quickly But you're right, vaccine will cause adverse effects and we have to be careful to test the safety (phase I) first. In this phase I trial, all subjects are below 60. In the ongoing phase II trial, some subjects are over 60, the eldest being 84. Let's see what results will be.

Thanks for the response. Phase II should be interesting.... That's a brave 84 year old! ;)
 
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Was reading through the paper linked above and noticed the following regarding side effects of the vaccine:
Between 42% and 56% of the participants reported a fever. Between 6 and 17% reported a Grade 3 fever. I found one reference to a grade 3 fever definition which was a temperature of 104 or higher for less than 24 hours. Is that the same definition as used in the paper???? (The Discussion section in the paper apparently refers to it as severe fever, stating these reactions were, "transient and self-limiting." I'm no doc, but a 104 plus temperature sounds frightening to me, especially in older folks. (The paper said 60 was the upper age range of participants, but doesn't list the age of those who experienced a Grade 3 fever.) Wouldn't that kind of reaction be a concern for older patients getting this kind of vaccination? (I realize even a vaccine only younger people took, would still reduce the likelihood of infections for the non-vaccinated.)



There was this in the Discussion section:

Takyu, you are correct. I had to go look all this up myself. Apparently the standards for describing adverse reactions in clinical trials is universal. A Grade 3 adverse reaction fever is very severe, but according to the definitions for clinical trials, not considered life threatening. In every case in this study where people had that reaction it revolved in one or two days, but one person had an even worse reaction and must have felt really awful for awhile. It happened in 2, 2 or 5 out of 36, 36 and 36 people tested at each dose of the vaccine. My guess is that this is because of the use of the viral vector (this is a DNA vaccine as I described above). I hope it can be refined a bit! Not sure I would relish going through that!

I am awaiting results of vaccine trials using more conventional methods.
 
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Takyu, you are correct. I had to go look all this up myself. Apparently the standards for describing adverse reactions in clinical trials is universal. A Grade 3 adverse reaction fever is very severe, but according to the definitions for clinical trials, not considered life threatening. In every case in this study it revolved in one or two days, but one person had an even worse reaction and must have felt really awful for awhile. My guess is that this is because of the use of the viral vector (this is a DNA vaccine as I described above). I hope it can be refined a bit! Not sure I would relish going through that!

I am awaiting results of vaccine trials using more conventional methods.

Thx for your response Baal. I was wondering whether it could be refined. And I am pretty sure I would not want to experience a 104 degree fever! If the odds were lower, as it is for the side effects of most influenza vaccines (where I've bothered to read the side effects) it wouldn't bother me, but when a severe side effect is listed as greater than 1 percent (rather than a small fraction of one percent) it concerns me.

Also, as you noted, the severe fever lasted for a day or two, but for people with even mild chronic kidney disease, diabetes, etc., is that kind of reaction tolerable (not a rhetorical question)? I do not know.

And as you alluded to, I hope something more conventional or with much lower potential for severe side effects is developed soon.
 
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My thoughts too Takyu. But we will see results from other vaccine trials before long. As I noted above, vaccine trials take awhile. I am also a bit nervous about using viral vectors to deliver a vaccine because it is more likely to yield an adverse reaction. I suspect (but obviously don't know) that vaccines based on recombinant proteins will produce fewer adverse reactions. But the would definitely take longer to scale up.
 
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I decided that, since the subject of how Sweden has chosen to try and respond to the virus is veering towards political subjects, that I would simply remove those posts so that the thread stays on the subject of vaccines and treatments and not how different governments should approach policy.

Thank you for understanding.
 
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The randomized clinical trial on remdesevir was published yesterday in the New England Journal of Medicine. This had been announced earlier but here are the peer- reviewed results. It's not a gigantic effect.

These results were data blinded earlier than the end of the study reporting findings from
an analysis that showed shortened time to recovery in the remdesivir group.

Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to
placebo) with data available after randomization indicated that those who received
remdesivir had a median recovery time of 11 days (95% confidence interval [CI],
9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received pla-
cebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-
Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with
placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events
were reported for 114 of the 541 patients in the remdesivir group who underwent
randomization (21.1%) and 141 of the 522 patients in the placebo group who un-
derwent randomization (27.0%).
CONCLUSIONS
Remdesivir was superior to placebo in shortening the time to recovery in adults
hospitalized with Covid-19 and evidence of lower respiratory tract infection.
(Funded by the National Institute of Allergy and Infectious Diseases and others;
ACCT-1 ClinicalTrials.gov number, NCT04280705.)
 
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Here is an article in one of the most prestigious scientific journals on why you should wear masks indoors (when not at home). It is written for non-specialists.

I VERY strongly recommend reading this, it is not too long.

https://science.sciencemag.org/cont...2qMak5BxyeAneQWrCirZsUrcGveFGWXeeWpFbCqfc5tbw

I was just going to post this article and ask the experts. Sure seems pretty convincing on how easily this virus is spread.

Another question. What is the best data to assess the prevalence of COVID-19 in a community? I see lots of graphs and data on daily new cases, deaths, hospitalizations, etc., but wouldn't the number of active cases (positive tests, diagnosed, etc. but not yet recovered) be the better indicator? And then might need to multiply that by a factor of 2 or so to account for asymptomatic cases? Trying to figure the odds of one of the 20 or so regular players being a carrier, or having had recent contact with a carrier. Probably too much of a risk.
 
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To be honest, I'm not sure where to get good local information.The John's Hopkins site does have state by state data. I know for a fact authorities in some places (like Florida) are intentionally suppressing that information on their own websites. Of course it depends too on how much testing is being done. I think we are flying blind in a lot of places, more so as things open up. Wish I had more to offer.
 
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What is the best data to assess the prevalence of COVID-19 in a community? I see lots of graphs and data on daily new cases, deaths, hospitalizations, etc., but wouldn't the number of active cases (positive tests, diagnosed, etc. but not yet recovered) be the better indicator? And then might need to multiply that by a factor of 2 or so to account for asymptomatic cases? Trying to figure the odds of one of the 20 or so regular players being a carrier, or having had recent contact with a carrier. Probably too much of a risk.
The best data to assess current prevalence isn't available for most communities. That would be PCR test results from a sufficiently large randomly selected population sample. You can estimate prevalence using various epidemiological models, but I wouldn't recommend it even if you're an epidemiologist. Not enough reliable data.


You might get a qualitative idea of your background risk (low, medium or high) by looking at trends in reported deaths and new hospitalizations in your community. If these numbers are rising (look at rolling averages over several days or a week, ignore day to day fluctuations), you should probably assume at least medium risk. Assume low risk only if you trust that the actual numbers are very small relative to population size and the trends are flat or declining.
 
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Randomized double-blind placebo controlled clinical trial on whether hydroxychloroquine (HQ) prevents people from getting Covid-19 was published in New England Journal of Medicine. Subjects were asymptomatic but had been exposed to someone with Covid-19

HQ doesn't have any discernible effect. In the data supplement there is data showing that adding zinc or Vitamin C on top of HQ didn't work either.

Patients were relatively young and no arrythmias occurred. Maybe we can drive a silver stake through the heart of this idea now.


https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
 
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