Coronavirus: What questions do you have?

[cwbullet]

Is that a CVVHD-based device?

Yes. I know I am over simplifying it.

 

[OverTheTop]

No worries . My wife is an ex-ICU nurse and I helped her through her studies.

 

[cwbullet]

New research and COVID news:

1. Several of vaccine should provide significant protection against all of the current 30+ COVID 19 mutations. The evidence is clear in several of the vaccines in Phase 3 trials.
2. High risk activities - large (10 plus people) gatherings and drinking or eating in restaurants. Cases that are traced find this as a common lapse. Go figure, you have to remove the mask to drink or eat.
3. The better the ventilation the lower the risk of COVID. Packed elevators are a higher risk.
4. Army has found that the virus effects the myocardium and limits Activity Duty cardiovascular fitness. This appears to be a direct effect from the virus through ACE II receptors in the hard muscle. They are developing a return to duty plan for those that catch the virus. This could have a significant effect on athletes. Specialists think this could require a 6 month reduction in activity.
5. There is a significant impact of people being non-compliant with isolation. There are multiple clusters. One was reported in Europe as infecting 100s. The civilian might be charged for endangering the public and may found culpable. If convicted, they might receive decades in jail. The civilian is a US citizen.

Number continue to be down in GA. We are consistently at 1000-2500 per day. This is down from 3000-4000 per day.

 

[boatgeek]

Update on the Moderna and Pfizer vaccine timelines.

First, Moderna. They are just about to having 30K people enrolled in their trial. I don't know if that means that they've actually vaccinated them or they're signed up. When they reach 53 COVID infections in their trial group, they'll review data. If most of the infections are in the placebo group, they'll apply for an EUA. Otherwise, they'll re-assess data at 106 cases and then again at 151 cases. Moderna currently expecting that 53-infection milestone to happen in November, but it may be in October.

Pfizer has enrolled 29K participants enrolled and "expects to have enough data to know whether the vaccine works by the end of October."

https://www.reuters.com/article/hea...-19-vaccine-based-on-early-data-idUSL1N2GD2N8

 

[Marc_G]

How long does an EUA take to process?

There are three processes to consider:

1. Pharma company internally reviews data, possibly leading to decision to file EUA.
2. They have to creat a data package to go with their submission. Normally this takes weeks/months, but in this case I'm sure a lot of it can be prepared in advance, just pending the data dump.
3. Then they submit to the FDA who have to review the data. I can't see this review taking less than a week or two. Even for a vaccine there is a lot of data. Has anyone seen an estimate for this?
4. FDA may have follow-up questions or require additional analysis to be conducted.

 

[Peartree]

How long does an EUA take to process?

There are three processes to consider:

1. Pharma company internally reviews data, possibly leading to decision to file EUA.
2. They have to creat a data package to go with their submission. Normally this takes weeks/months, but in this case I'm sure a lot of it can be prepared in advance, just pending the data dump.
3. Then they submit to the FDA who have to review the data. I can't see this review taking less than a week or two. Even for a vaccine there is a lot of data. Has anyone seen an estimate for this?
4. FDA may have follow-up questions or require additional analysis to be conducted.

Further questions in this regard,:

First, wouldn't an EUA take longer simply because their RNA technology/biology/method is new(ish) and less proven than some of the other vaccine methods?

Second, I think I read that Moderna's vaccine is one of the two or three types that have to be maintained at a ridiculously low temperature (one, I don't recall which, had to be stored at something like minus 79 degrees F.) that will be difficult (or impossible) for many traditional clinics/pharmacies to transport and maintain. Is that likely to make approval for an EUA more difficult or "just" additionally complicate distribution?

 

[Marc_G]

Hi Chuck, here's a question:

Check out this article:
https://www.yahoo.com/news/measures...tists-want-to-keep-it-that-way-182216307.html
Specifically:

"The weekly average of positive lab results is now 0.2 percent, compared with 2.35 percent in 2019. The positive rate is usually between 1 and 2 percent. "

So, if it's normally 1-2% this time of year, and it's 0.2% now, that means the amount of flu circulating is about 1/5 to 1/10 normal. Flu and COVID-19 spread the same way: people breathe on each other and spread droplets when they talk, cough, sneeze, pick their noses... We are using masks and social distancing this year, and from the numbers above, this has contributed to a dramatic 5-10x reduction in the flu prevalence. Since flu and COVID-19 spread the same way, it's reasonable to conclude that at least to an approximation, the distancing measures we are taking are having a similar effect on COVID-19 spread as is being seen on influenza.

So Chuck, is it reasonable to conclude that the measured impact on influenza spread can be used as a strong proxy to extrapolate how much more COVID-19 spread there would be if we hadn't been doing lockdowns and social distancing and masks and such?. There may be subtle differences between effectiveness of masks and other distancing measures between flu and COVID-19, but in my view they should be in the same ballpark since the key in both cases is droplet containment. So, by this logic, if the US hadn't done what it did, we might be seeing 5x-10x as many infectious people circulating. I think it's actually more complicated than this, since flu and COVID-19 have different replication values (so, the impact may be stronger for COVID).

But ballparking it, does this seem to be a reasonable line of logic?

It's also interesting to note that Sweden did relatively little early on to blunt the virus, whereas it's neighbors with similar ways of life Finland and Norway did a lot, and over that period Sweden had 10x the cases and death rate per capita as those countries that took it more seriously.

Thoughts?

 

[Stefan2k4]

New research and COVID news:

1. Army has found that the virus effects the myocardium and limits Activity Duty cardiovascular fitness. This appears to be a direct effect from the virus through ACE II receptors in the hard muscle. They are developing a return to duty plan for those that catch the virus. This could have a significant effect on athletes. Specialists think this could require a 6 month reduction in activity

That's interesting. Are there any studies being done into whether ACE inhibitors or ARBs might be useful in reducing or preventing this damage?

 

[BABAR]

Would health care providers qualify as “high risk groups” for EUA?

Would their immediate family also qualify?

 

[cwbullet]

How long does an EUA take to process?

I do not think there is a universal answer to this. Weeks to months prior to COVID, but now it is expedited. One project, we use tools days. Many of those quickly approved have other applications - see eBola.

 

[cwbullet]

Hi Chuck, here's a question:

Check out this article:
https://www.yahoo.com/news/measures...tists-want-to-keep-it-that-way-182216307.html
Specifically:

"The weekly average of positive lab results is now 0.2 percent, compared with 2.35 percent in 2019. The positive rate is usually between 1 and 2 percent. "

So, if it's normally 1-2% this time of year, and it's 0.2% now, that means the amount of flu circulating is about 1/5 to 1/10 normal. Flu and COVID-19 spread the same way: people breathe on each other and spread droplets when they talk, cough, sneeze, pick their noses... We are using masks and social distancing this year, and from the numbers above, this has contributed to a dramatic 5-10x reduction in the flu prevalence. Since flu and COVID-19 spread the same way, it's reasonable to conclude that at least to an approximation, the distancing measures we are taking are having a similar effect on COVID-19 spread as is being seen on influenza.

So Chuck, is it reasonable to conclude that the measured impact on influenza spread can be used as a strong proxy to extrapolate how much more COVID-19 spread there would be if we hadn't been doing lockdowns and social distancing and masks and such?. There may be subtle differences between effectiveness of masks and other distancing measures between flu and COVID-19, but in my view they should be in the same ballpark since the key in both cases is droplet containment. So, by this logic, if the US hadn't done what it did, we might be seeing 5x-10x as many infectious people circulating. I think it's actually more complicated than this, since flu and COVID-19 have different replication values (so, the impact may be stronger for COVID).

But ballparking it, does this seem to be a reasonable line of logic?

It's also interesting to note that Sweden did relatively little early on to blunt the virus, whereas it's neighbors with similar ways of life Finland and Norway did a lot, and over that period Sweden had 10x the cases and death rate per capita as those countries that took it more seriously.

Thoughts?

Wow - that is a lot to comment on. The percentages you quote found right. I cannot explain them but I wonder if we were over testing this year and it lowered the percentage.

I am not sure what to think fo the lower positive testing rates for Flu. I think it is multifactorial. First, Flu testing at this moment is often ignored in favor of testing for Just COVID. The joint testing is not universally available so you often have to do 2 swabs (one covid, one flu). Swabs are in short supply so we test for just COVID. This testing priority is based on the theory that flu is less prevalent than Covid.

I do think the mask is going to reduce flu infections. Right now, I am developing protocols to determine when and if to test for both, just covid, and just flu. When available, we will have a 4 virus and 6-12 virus panel off one swab. The 4 virus will be available in NOV.

 

[cwbullet]

That's interesting. Are there any studies being done into whether ACE inhibitors or ARBs might be useful in reducing or preventing this damage?

It has been done and is conflicting. I suspect the effect is minimal.

 

[cwbullet]

Would health care providers qualify as “high risk groups” for EUA?

Would their immediate family also qualify?

Health care workers will be a priority prior to the high risk. Families likely will not.

I know this is harsh, but we are immunizing health care workers in the front line to protect them as they vaccinate and give care. We want to prevent absenteeism and protect the "force". Families are important, but they often do not contribute to that directly.

 

[Marc_G]

Health care workers will be a priority prior to the high risk. Families likely will not.

I know this is harsh, but we are immunizing health care workers in the front line to protect them as they vaccinate and give care. We want to prevent absenteeism and protect the "force". Families are important, but they often do not contribute to that directly.

It's important to prioritize the front line workers for sure. Once they are protected, it keeps their families safe and prevents spread from care giver to patients.

 

[cwbullet]

It's important to prioritize the front line workers for sure. Once they are protected, it keeps their families safe and prevents spread from care giver to patients.

True, protection indirectly. I think it is important in a pandemic for healthcare workers to protect their families through good hygiene.

 

[Bill S]

Health care workers will be a priority prior to the high risk. Families likely will not.

I know this is harsh, but we are immunizing health care workers in the front line to protect them as they vaccinate and give care. We want to prevent absenteeism and protect the "force". Families are important, but they often do not contribute to that directly.

The trick is if said provider's family gets sick, they can easily pass it on to the provider. Example: my wife is a retail pharmacist, and she is at least medium risk despite the precautionary measures her company has enacted (she is immuno-compromised due to medication for psoritic arthritis). Our son is back in school, so it's possible he could pick Covid up there, and bring it home, infecting us both. End result is a provider out of action for a long time, maybe permanently.

 

[cwbullet]

I am a provider but will probably not be eligible. I do Not spend 50% of my time in direct patient contact.

Update from research:

1. New treatment near release - monoclonal Antibodies given to symptomatic non-admitted patient and resulted reduced admission and ER visits.
2. Screening at entrances has been proven ineffective to prevent infections. Temperature checks appear to be useless At presenting infections. Data appears to show that universal masks are more effective than screening or vaccination.
3. Glasses seem to be effective at reducing infections and the severity of infections. Seems to point to the eyes being a source or site of initial infection.

 

[rocketsaway]

I am a provider but will probably not be eligible. I do Not spend 50% of my time in direct patient contact.

Update from research:

1. New treatment near release - monoclonal Antibodies given to symptomatic non-admitted patient and resulted reduced admission and ER visits.
2. Screening at entrances has been proven ineffective to prevent infections. Temperature checks appear to be useless At presenting infections. Data appears to show that universal masks are more effective than screening or vaccination.
3. Glasses seem to be effective at reducing infections and the severity of infections. Seems to point to the eyes being a source or site of initial infection.

Is this treatment, you speak of, is it Regeneron's REGN-COV2 ?

 

[cwbullet]

Is this treatment, you speak of, is it Regeneron's REGN-COV2 ?

There a couple that has similar results. That is one of them that had positive returns.

 

[Marc_G]

Chuck, I'm relieved to hear FDA is considering specific science driven approaches to EUA approvals for vaccines. Do you have any comments on what is proposed here (but not yet ratified).

https://www.cnn.com/2020/09/22/health/coronavirus-vaccine-fda-authorization-rules/index.html

 

[cwbullet]

Chuck, I'm relieved to hear FDA is considering specific science driven approaches to EUA approvals for vaccines. Do you have any comments on what is proposed here (but not yet ratified).

https://www.cnn.com/2020/09/22/health/coronavirus-vaccine-fda-authorization-rules/index.html

Update: You hear it here first, The vaccine will be available no later than the end of November. I reviewed data today. Announcement to come soon.

 

[afadeev]

Update: You hear it here first, The vaccine will be available no later than the end of November. I reviewed data today. Announcement to come soon.

Cool.
What's the expected/projected effectiveness rate?

 

[Marc_G]

How do they do it so quickly when half the participants haven't even gotten their second shot?

 

[NateB]

Hopefully this means efficacy was proven with one dose.

 

[Marc_G]

Hopefully this means efficacy was proven with one dose.

Still seems like a rush on the safety side.

 

[Cl(VII)]

A summary of the protocols that includes how many infections would be needed to show efficacy to different levels: https://blogs.sciencemag.org/pipeline/archives/2020/09/21/the-vaccine-protocols

The FDA was clear (at least plans to be from the leaks) that safety will need to be demonstrated base on 2 months post second dose, which for Pfizer will likely be done in mid Nov. Efficacy can be evaluated earlier, and safety confirmed later instead of waiting for the entire thing at once. The EUA would be granted after both are shown, but they can be evaluated as available.

Were I a betting man my money would be on Pfizer to win the race (they are ahead on enrollment, they plan to enroll more total, their preclinical data looks the strongest to me, their first interim analysis is earlier than Moderna, and they been-there-done-that on large trials before), which would make this paragraph relavent: "As for Pfizer/BioNTech, they have a somewhat more aggressive approach. They calculate that they’ll hit 164 cases by the end of the study, and they have four IAs planned, at 32, 62, 92, and 120 cases. If they can reject the null hypothesis at that first one, that will be considered “overwhelming efficacy”, with a VE of at least 77%."

IA is interim analysis. VE is Vaccine Efficacy

Again, for what my opinion is worth, I would guess that Pfizer (and Moderna) are going to achieve VE well over 77% based on the P1 and P2 data. I wouldn't be shocked if they approach 90%.

 

[Mushtang]

What's the downside to taking one of these vaccinations soon if it turns out in 6 months that it doesn't meet whatever levels are normally needed to accept a vaccine?

For instance, does it just mean that you may not actually be vaccinated but think that you are? If that's the worst thing then I'd definitely sign up and keep wearing masks and social distancing.

Or maybe it keeps you from taking the actual vaccine when it's proven to work a couple of months later, and now you have to remain unvaccinated for a longer period of time? That seems unlikely to me.

Surely the risk isn't that it would be directly unhealthy to you if it turns out not to work (as opposed to allowing you to still get infected). Also seems very unlikely.

 

[BABAR]

Any opinion of the reported unreliability of Chinese KN95 masks?

I am wondering if the ear loops are the issue, hard to get a good seal.


https://www.usatoday.com/story/news...ed-china-dont-meet-standards-ecri/5806327002/

 

[Marc_G]

And

What's the downside to taking one of these vaccinations soon if it turns out in 6 months that it doesn't meet whatever levels are normally needed to accept a vaccine?

For instance, does it just mean that you may not actually be vaccinated but think that you are? If that's the worst thing then I'd definitely sign up and keep wearing masks and social distancing.

Or maybe it keeps you from taking the actual vaccine when it's proven to work a couple of months later, and now you have to remain unvaccinated for a longer period of time? That seems unlikely to me.

Surely the risk isn't that it would be directly unhealthy to you if it turns out not to work (as opposed to allowing you to still get infected). Also seems very unlikely.

My personal concern isn't with effectiveness ("does it prevent COVID-19?") as that data is easy to collect and interpret, and a statistical measure of effectiveness could come quite early, well before the whole patient cohort gets all their shots. There are lots of reasons to believe the vaccine should be strongly effective.

My concern is "are there significant side effects from getting the shot?" The ONLY way to know this is to give all 30k people their two shots (something like half get a placebo, not the new vaccine), wait TWO MONTHS and then review the placebo/vaccine groups to see if any negative outcomes seem stronger in the vaccine group. This vaccine uses a technology not previously deployed in a human vaccine (uses mRNA to get human cells to produce the protein antigen that induces our immune cells to generates antibodies against). The reason we do clinical trials is to collect the safety data as well as the efficacy data. While efficacy data can be evaluated early, if there is a strong signal, safety data requires that all the patients receive all their doses the same way the vaccine will be deployed (this should be done in November), and then time to collect any events afterward for a period of two months (into early January). Even if all doses were done by end of September, safety data could be generated for review at end of November, and then review could commence.

I'm unaware of how this can play out faster than this timeline without compromising the safety data collection. Even if they were looking at just one dose as being effective, that takes a month out but I don't think all patients have even gotten their first shot now...

Clearly Chuck knows more than us, so I anxiously await the news. With the death rate in US creeping back up, over 800/day last time I looked, time is lives. I just don't want something to be pushed through that later is shown to have serious side effects down the road.

 

[Bill S]

Is there any info out there how these various vaccine contenders would work in people with weak/suppressed immune systems? Myself, I have an suppressed immune system due to having had Lyme Disease. My white counts were normally in the 7-8 range, now they are typically 3.5 to 4.5. My doc, an rheumatologist and internist, said that he though that I was producing more white cells than that, but that many of them seemed to hang around the tick bite site in the tissues rather than being in the circulatory system. Which might explain why that area of my skin continues to show a red blotchy area frequently, despite it being 13 years since I was "cured".

The wife, she is on immunosuppressant drugs for psoritic arthritis, and so she can't take live vaccines, and she has to be super careful to not get sick.