COVID-19 Pandemic: Transmissions, Deaths, Treatments, Vaccines, Interventions and More...

[Upstream]

Getting back to remdesivir, let's hope the unblinding brings good news.

I haven't seen anything on the results of the remdesivir trial that completed yesterday. The lack of news is disappointing, but in some ways promising. If the trial showed great positive results, they would have halted the trial early, or at least provided some data yesterday. On the other hand, if the trial was an obvious failure, that would have come out yesterday. My guess is the data showed mixed results, and they are now doing a deep dive to see if they can find promising segments, for example, positive results for patients before or after a point in time.

 

[RU2055]

I haven't seen anything on the results of the remdesivir trial that completed yesterday. The lack of news is disappointing, but in some ways promising. If the trial showed great positive results, they would have halted the trial early, or at least provided some data yesterday. On the other hand, if the trial was an obvious failure, that would have come out yesterday. My guess is the data showed mixed results, and they are now doing a deep dive to see if they can find promising segments, for example, positive results for patients before or after a point in time.

It's not open label, it's blinded data, so it will take time to analyze after they unblind. My guess is 1 to 2 weeks. It will also take longer if they expanded the protocol to add more patients.

Also, and as you mentioned, disease progression is an important element in evaluating efficacy. There are several trials for remdesivir registered in ClinTrials.gov. The April 3 one is for "severe" cases. There are other trials for moderate cases. I'm not sure what the end points are but I am actually expecting mixed results. JMHO. I say this only because for patients whose disease has progressed to cytokine stage will not be helped by remdesivir.

Ultimately, there won't be a silver bullet but rather a combination of anti-viral/IL-6 anatgonist "cocktail" as the therapy for those with severe cases. JMVHO - HCQ for early stage, remdesivir for moderate and then anti-viral/IL-6 antagonist for severe cases, is how I see things playing out for the future until a vaccine arrives.

 

[RU2055]

Here is one anti-viral/IL-6 cocktail in the works ........

http://www.pmlive.com/pharma_news/s...f_arthritis_drug_kevzara_for_covid-19_1329326

Regeneron's anti-viral .......

https://www.fiercebiotech.com/resea...-trial-for-covid-19-antibody-cocktail-therapy

Regeneron's EB3, outperformed remdesivir in an Ebola trial back in 2019 ..... maybe it will do the same for COV-19

https://www.nejm.org/doi/full/10.1056/NEJMoa1910993

 

[RU2055]

Because of the high demand for compassionate use, they opened up 6 locations here, 3 in NY and 3 in NJ for patients to enroll in the amended and expanded clinical study protocol.

https://clinicaltrials.gov/ct2/show/NCT04323761?cond=remdesivir&draw=2&rank=4

EMA is allowing remdesivir to be administered broad based to critically ill patients rather than the compassionate use per patient approval process, thus removing red tape.

https://www.ema.europa.eu/en/news/ema-provides-recommendations-compassionate-use-remdesivir-covid-19

 

[Upstream]

It's not open label, it's blinded data, so it will take time to analyze after they unblind. My guess is 1 to 2 weeks. It will also take longer if they expanded the protocol to add more patients.

Also, and as you mentioned, disease progression is an important element in evaluating efficacy. There are several trials for remdesivir registered in ClinTrials.gov. The April 3 one is for "severe" cases. There are other trials for moderate cases. I'm not sure what the end points are but I am actually expecting mixed results. JMHO. I say this only because for patients whose disease has progressed to cytokine stage will not be helped by remdesivir.

Ultimately, there won't be a silver bullet but rather a combination of anti-viral/IL-6 anatgonist "cocktail" as the therapy for those with severe cases. JMVHO - HCQ for early stage, remdesivir for moderate and then anti-viral/IL-6 antagonist for severe cases, is how I see things playing out for the future until a vaccine arrives.

My point is that they should have already had an independent data management team looking at the unblinded data, so they would already know if there was a strong positive or negative signal. The lack of news is an indication that there is no strong signal either way. Thus they need more time to do a deeper analysis.

I think your assessment is reasonable, that if remdesivir shows benefit, it will mostly be for those who have progressed to moderate, but not severe, stage.

 

[ArminRU]

Here is one anti-viral/IL-6 cocktail in the works ........

http://www.pmlive.com/pharma_news/s...f_arthritis_drug_kevzara_for_covid-19_1329326

Regeneron's anti-viral .......

https://www.fiercebiotech.com/resea...-trial-for-covid-19-antibody-cocktail-therapy

Regeneron's EB3, outperformed remdesivir in an Ebola trial back in 2019 ..... maybe it will do the same for COV-19

https://www.nejm.org/doi/full/10.1056/NEJMoa1910993

Saw an article on the first one yesterday. We’ll find out more by month end.

https://seekingalpha.com/news/3558336-regeneron-sees-covidminus-19-treatment-results-april-end

https://seekingalpha.com/news/3558341-regeneron-launches-studies-of-kevzara-for-covidminus-19

 

[Proud NJ Sports Fan]

Red tape is not a bad thing. I am no we want a cure, but there is no way in hell I am putting something in my body that I don’t know Is safe. Especially if I know anyone in this administration is involved with any of the decisions.

If it weren’t from red tape we’d have the virus and most likely a complete failure in the banking system. We’d probably have 2007-09 and today wrapped up as one. Red tape is why the banks are strong now.

Bad post

 

[RU2055]

Saw an article on the first one yesterday. We’ll find out more by month end.

https://seekingalpha.com/news/3558336-regeneron-sees-covidminus-19-treatment-results-april-end

Maybe even sooner, trial ended 3/30 and now they’re reviewing results.
https://seekingalpha.com/news/3558341-regeneron-launches-studies-of-kevzara-for-covidminus-19

Not sure where the seeking alpha people are getting their info from. According to clinicaltrials.gov, the trial for Kevzara just started on March 28. The trial will conclude in July.

https://clinicaltrials.gov/ct2/show/NCT04327388?cond=Kevzara&draw=2&rank=3

Nevertheless, front line doctors have started giving Kevzara (or the Roche drug, Actemra) as an IL-6 anatgonist for compassionate use, in combination with remdesivir and HCQs for patients in very severe state.

 

[ArminRU]

Not sure where the seeking alpha people are getting their info from. According to clinicaltrials.gov, the trial for Kevzara just started on March 28. The trial will conclude in July.

https://clinicaltrials.gov/ct2/show/NCT04327388?cond=Kevzara&draw=2&rank=3

Nevertheless, front line doctors have started giving Kevzara (or the Roche drug, Actemra) as an IL-6 anatgonist for compassionate use, in combination with remdesivir and HCQs for patients in very severe state.

Whoops, read it wrong. Starting this month, but data should still start trickling out in a few weeks.

 

[Greene Rice FIG]

Bad post

How so

 

[LETSGORU91]

"Interleukin 6 (IL-6) seems to hold a key role in CRS pathophysiology since highly elevated IL-6 levels are seen in patients with CRS". IL-6 binding agents are starting to get used in combination with antivirals and chloroquine. I'm very interested in how well disrupting the release of IL-6 will reduce the effects of CRS.

 

[RU848789]

Some great progress being made on serological antibody tests at Mass General. Have to click on "see replies" in the lower left hand corner of the tweet (at least I did - I could only see the title slide). Looks like infected patients don't show measurable antibodies until about 7 days after symptom onset and younger people had faster antibody growth rates (separate slide) and immunosuppressed people had the slowest growth rates (the two black circles in the grey shaded part of the graphic below).

The red "healthy convalescent" dot represents a patient given the convalescent plasma with antibodies treatment (didn't think they were doing that at Mass General, though - maybe they were sent a sample from NYC). Was also good to see they now have confidence in the accuracy of the antibody assays (including developing a better ELISA assay themselves; ELISA is "enzyme-linked immunosorbent assay" a plate-based assay technique designed for detecting and quantifying substances such as peptides, proteins, antibodies and hormones).

 

[RU848789]

#s. Appreciate all the data, information and sober analysis you bring [along with others] to this thread. It’s a daily must read for me. Most recognize that the more testing that occurs the better identification of the segment of population that needs medical attention or needs to be separated from the greater population; and which segment is now immune and can go about their lives.

Question: What are your thoughts on reports that some testing is producing false negatives (1 in 3)? And whether the quality, manner and volume of testing we’re beginning to see will diminish the inaccuracies of test results?

Thanks again.

GO RU

Thanks. False negatives have been a known problem with the RT-PCR viral test (same for influenza) since at least mid-February and yes there are estimates that up to 30% could be false negatives, meaning they are infected, but the test does not detect it. False negatives are exactly what you don't want in a test, as you'd rather over-protect than under-protect with an epidemic. False positives are pretty rare, i.e., if you test positive, you have it.

This is why, though, doctors tell people, especially those with symptoms, to assume they have the virus (and self-quarantine) despite any negative test - at least until symptoms go away. It's not a great situation, but it's reality for now. I have no idea if the false negative rates are similar across all the different PCR viral tests out there (and there are many) or what the technical limitations are to improving the sensitivity of the test.

https://www.livescience.com/covid19-coronavirus-tests-false-negatives.html

https://www.medrxiv.org/content/10.1101/2020.02.11.20021493v2

 

[satnom]

Thanks. False negatives have been a known problem with the RT-PCR viral test (same for influenza) since at least mid-February and yes there are estimates that up to 30% could be false negatives, meaning they are infected, but the test does not detect it. False negatives are exactly what you don't want in a test, as you'd rather over-protect than under-protect with an epidemic. False positives are pretty rare, i.e., if you test positive, you have it.

This is why, though, doctors tell people, especially those with symptoms, to assume they have the virus (and self-quarantine) despite any negative test - at least until symptoms go away. It's not a great situation, but it's reality for now. I have no idea if the false negative rates are similar across all the different PCR viral tests out there (and there are many) or what the technical limitations are to improving the sensitivity of the test.

https://www.livescience.com/covid19-coronavirus-tests-false-negatives.html

https://www.medrxiv.org/content/10.1101/2020.02.11.20021493v2

Thank you. From what I’m reading it’s best to assume you have if you have symptoms but is there a compelling number of individuals that have been tested as negative but are asymptomatic [assuming they were able to get tested even though no symptoms were shown which by all accounts is a rarity since doctors are directing asymptomatic patients not to go to the hospital or be turned away because of no symptoms; but possibly have the means (I.e. pro athlete, essential worker, etc)] and therefore are carriers that can infect others?

Do you see a particular test method currently being used or on its way that will eliminate false negatives, scalable, mass produced and able to produce results relatively quickly [within hours or less]?

Thanks again.

GO RU

 

[RU848789]

Latest tweet from Gov Murphy. Unfortunately, NJ's projected peak looks to be greater than originally thought, peaking at near 100 deaths per day in 5 days; problem is there were 200 deaths in NJ yesterday, so not sure what to make of it.

 

[RU848789]

Thank you. From what I’m reading it’s best to assume you have if you have symptoms but is there a compelling number of individuals that have been tested as negative but are asymptomatic [assuming they were able to get tested even though no symptoms were shown which by all accounts is a rarity since doctors are directing asymptomatic patients not to go to the hospital or be turned away because of no symptoms; but possibly have the means (I.e. pro athlete, essential worker, etc)] and therefore are carriers that can infect others?

Do you see a particular test method currently being used or on its way that will eliminate false negatives, scalable, mass produced and able to produce results relatively quickly [within hours or less]?

Thanks again.

GO RU

My guess is no, since I would think we'd already have such a test if it were easy to develop, given the false negative problem has been known for awhile.

 

[wisr01]

"Interleukin 6 (IL-6) seems to hold a key role in CRS pathophysiology since highly elevated IL-6 levels are seen in patients with CRS". IL-6 binding agents are starting to get used in combination with antivirals and chloroquine. I'm very interested in how well disrupting the release of IL-6 will reduce the effects of CRS.

https://nypost.com/2020/04/04/long-island-doctor-tries-new-hydroxychloroquine-for-covid-19-patients/

After reading this he might have stumbled on something.

Doxycycline has an effect on IL-6.
https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=40645
https://aac.asm.org/content/aac/47/11/3630.full.pdf

Doxycycline modify the cytokine storm in patients with dengue and dengue hemorrhagic fever
https://www.researchgate.net/public...ents_with_dengue_and_dengue_hemorrhagic_fever

Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels.
https://www.ncbi.nlm.nih.gov/pubmed/25858261

FYI, cytokine storm is what kills CV19 patients.

HydroxyChloroquinine in vitro study.
https://www.nature.com/articles/s41421-020-0156-0

I wonder if we should also take a look at clarithromycin as it has an even greater effect on IL-6 than Azithromycin. At least that is what I remember reading a long time ago.


https://www.vox.com/2020/3/12/21176...eaths-china-treatment-cytokine-storm-syndrome

 

[DJ Spanky]

EMA is allowing remdesivir to be administered broad based to critically ill patients rather than the compassionate use per patient approval process, thus removing red tape.

Given the likelihood of death amongst critically ill patients, this makes a helluva lot of sense.

Latest tweet from Gov Murphy. Unfortunately, NJ's projected peak looks to be greater than originally thought, peaking at near 100 deaths per day in 5 days; problem is there were 200 deaths in NJ yesterday, so not sure what to make of it.

Very easy to have spikes on singular days, let's see what the trend is over the next few days.

Something I've noticed and hasn't been commented on as far as I can tell, is the rise in deaths the last few days in Spain, France and the UK. I fully expected to see it in Spain, but not in the other 2 countries.

 

[cohwx]

Something I've noticed and hasn't been commented on as far as I can tell, is the rise in deaths the last few days in Spain, France and the UK. I fully expected to see it in Spain, but not in the other 2 countries.

The numbers from many of the European countries are crazy. Spain CFR 9.4%, Italy 12.3%, France 8.4%, UK 10.3%, Netherlands 9.9%. Of course that is not the infection fatality rate and we don't know what their testing criteria are like, but those are all high rates.

US sitting at 2.7% for now. Is that more realistic or are we about to see a massive increase in deaths? If we're further back on the curve compared to Europe we'll see a big increase in deaths over the next week or two especially in NYC.

 

[Upstream]

Latest tweet from Gov Murphy. Unfortunately, NJ's projected peak looks to be greater than originally thought, peaking at near 100 deaths per day in 5 days; problem is there were 200 deaths in NJ yesterday, so not sure what to make of it.

View embedded media

This may also be due to a timing issue of when the deaths are reported. The Governor indicated all the deaths reported today are not within the past 24 hours, because there is a backlog of testing, so some people who died previously and just had confirmed positive test results are now included in the count.

 

[satnom]

When we get out of this [God willing sooner rather than later] we really have to study how countries like Taiwan (80 miles off the coast of China and 2MM annual Chinese visitors) and South Korea were able to set up the proper protocols and systems to sound the alarm of the possible pandemic wave and arrested the problem early.

Taiwan has 5 deaths and South Korea 177 deaths to date respectively. That is a phenomenal job of controlling this scourge.

GO RU

 

[richthedentist]

The numbers from many of the European countries are crazy. Spain CFR 9.4%, Italy 12.3%, France 8.4%, UK 10.3%, Netherlands 9.9%. Of course that is not the infection fatality rate and we don't know what their testing criteria are like, but those are all high rates.

US sitting at 2.7% for now. Is that more realistic or are we about to see a massive increase in deaths? If we're further back on the curve compared to Europe we'll see a big increase in deaths over the next week or two especially in NYC.

2.7% is still probably way high because many people who may have Carona or may have had are not factored into the overall percentage

 

[retired711]

When we get out of this [God willing sooner rather than later] we really have to study how countries like Taiwan (80 miles off the coast of China and 2MM annual Chinese visitors) and South Korea were able to set up the proper protocols and systems to sound the alarm of the possible pandemic wave and arrested the problem early.

Taiwan has 5 deaths and South Korea 177 deaths to date respectively. That is a phenomenal job of controlling this scourge.

GO RU

I think a large part of it is that Taiwan and South Korea (especially the latter) are used to coping with epidemics (e.g. SARS) and so they are set up for events like this.

 

[RUhasarrived]

On Clyde Lewis' show last night,Morristown's Richard Hoagland says in 2 weeks he's going to have a guest on his radio show who has the proof that COVID-19 came from outer space.

That should be interesting-if the guy shows up at all.

 

[cohwx]

2.7% is still probably way high because many people who may have Carona or may have had are not factored into the overall percentage

It all depends on what "rate" you are using. Case fatality rate (CFR) will always be much higher than IFR (Infection fatality rate) unless you can identify every single infected person. That is true for the flu - if you get sick enough to be hospitalized your chance of dying "from the flu" is actually pretty high (5% or higher I think). Same with this disease - if you get sick enough to be tested or hospitalized your chance of dying is much higher than if you have a less severe illness. That's kind of obvious but gets lost in the shuffle sometimes. So it'll all depend on what "case" is defined as.

Certainly if 80% of all infections are minor or even asymptomatic, then the total chance of dying from covid will be much lower. Using current numbers it would be about 0.5% which is still higher than flu but much less scary than 10%.

That said, there are currently over 8,000 serious/critical cases in the US and a fair number of those won't make it. Deaths are a lagging indicator.

 

[Scarlet4Shore]

When we get out of this [God willing sooner rather than later] we really have to study how countries like Taiwan (80 miles off the coast of China and 2MM annual Chinese visitors) and South Korea were able to set up the proper protocols and systems to sound the alarm of the possible pandemic wave and arrested the problem early.

Taiwan has 5 deaths and South Korea 177 deaths to date respectively. That is a phenomenal job of controlling this scourge.

GO RU

My coworker’s sister in law moved to SK last summer. They were under strict quarantine very early on. WFH and could leave the house for an hour a day, but not every day.

 

[cohwx]

I think a large part of it is that Taiwan and South Korea (especially the latter) are used to coping with epidemics (e.g. SARS) and so they are set up for events like this.

Yeah, they set up the testing early, tested many and did effective contact tracing and quarantines before it got out of hand. Maybe they also got lucky to some degree, if South Korea hadn't identified that Church cluster early things may have played out differently there. That's part luck but also part being ready and testing.

They have to keep at it though, there are still new cases every day...going to be a long battle.

 

[satnom]

I think a large part of it is that Taiwan and South Korea (especially the latter) are used to coping with epidemics (e.g. SARS) and so they are set up for events like this.

SARS was a game changer for them. And COVID19 should be our watershed moment.

GO RU

 

[RUinPinehurst]

My old RU roomie who heads a healthcare system in NJ just indicated NJ's COVID-19 situation is not expected to peak for another 10 - 14 days. Given what they're dealing with now, the loss of life, that news is just unimaginable.

 

[RUJohnny]

My old RU roomie who heads a healthcare system in NJ just indicated NJ's COVID-19 situation is not expected to peak for another 10 - 14 days. Given what they're dealing with now, the loss of life, that news is just unimaginable.

Would make sense if cases peak in 5-7 for system overload and deaths to peak on a lag a week after.

 

[goru7]

When we get out of this [God willing sooner rather than later] we really have to study how countries like Taiwan (80 miles off the coast of China and 2MM annual Chinese visitors) and South Korea were able to set up the proper protocols and systems to sound the alarm of the possible pandemic wave and arrested the problem early.

Taiwan has 5 deaths and South Korea 177 deaths to date respectively. That is a phenomenal job of controlling this scourge.

GO RU

There was a piece on 60 minutes about it. They learned about it in late December and early January and didn’t believe anything coming out of China. They sent 2 of their top doctors to China to check the facts and social media was blowing up that people were dying like crazy and the crematoriums were working overtime. The doctors got back on January 20, and they shut down their country. Easier to do as each person via their cell phone had to check in and quarantine and record their temperature for 14 days . The piece was about a girl studying in London where it was getting out of control , and she said hopped on flight home to Taiwan, because The UK was a mess, and once home where she had to immediately do a 14 day quarantine after having her fever and other things checked at the airport . They tested everyone so no asymptomatic people spreading. That is why they only have 326 cases. Truly amazing because they were supposed to have the 2nd highest cases being so close to China. Their health minister said they learned from Sars and applied their lessons to stop the spread. That is why I say this has been an epic failure of testing. Not having it ready to test everyone especially having a month or two to get the tests. Failing to engage private companies to develop tests sooner , with the CDC screwup trying to develop their own test which failed has caused this spread.

 

[RUinPinehurst]

Would make sense if cases peak in 5-7 for system overload and deaths to peak on a lag a week after.

I believe the info he shared was the number of hospitalizations as a result of individuals having contracted the virus.

 

[RUJohnny]

I believe the info he shared was the number of hospitalizations as a result of individuals having contracted the virus.

I'll take the under. I don't think any of the modeling has our hospitalization peak as late as day 12, and Cuomo thinks they peak in NYC in 6 days. We shouldn't be that far behind the city.

 

[Proud NJ Sports Fan]

On Clyde Lewis' show last night,Morristown's Richard Hoagland says in 2 weeks he's going to have a guest on his radio show who has the proof that COVID-19 came from outer space.

That should be interesting-if the guy shows up at all.

I started a conspiracy theory thread in the CE board

 

[RU848789]

When we get out of this [God willing sooner rather than later] we really have to study how countries like Taiwan (80 miles off the coast of China and 2MM annual Chinese visitors) and South Korea were able to set up the proper protocols and systems to sound the alarm of the possible pandemic wave and arrested the problem early.

Taiwan has 5 deaths and South Korea 177 deaths to date respectively. That is a phenomenal job of controlling this scourge.

GO RU

There's no secret. Every advanced country knew what to do, i.e., what South Korea and others did - there was even a major worldwide pandemic simulation conducted in October 2019 (by Johns Hopkins, the World Economic Forum, and the Gates Foundation), featuring a new coronavirus pandemic killing 65 million people over 18 months around the globe. There was also a somewhat similar extended (ran over 6 months) tabletop exercise conducted by the US Department of Health and Human Services in the US in mid-2019, which highlighted all the shortcomings in preparedness in the US.

It's just that the US and most of Europe largely ignored the warnings of SARS and H1N1 and never truly prepared for a pandemic over the last ~17 years (at least), whereas several Asian countries were especially hit hard with SARS, which is part of why they were much better prepared. Despite decades of bipartisan poor planning in the US, we also could have decided to do much more and sooner than we did this time around....

https://nymag.com/intelligencer/202...virus-pandemic-in-2019-killed-65-million.html

https://www.nytimes.com/2020/03/19/us/politics/trump-coronavirus-outbreak.html

 

[LETSGORU91]

https://nypost.com/2020/04/04/long-island-doctor-tries-new-hydroxychloroquine-for-covid-19-patients/

After reading this he might have stumbled on something.

FYI, cytokine storm is what kills CV19 patients.

HydroxyChloroquinine in vitro study.
https://www.nature.com/articles/s41421-020-0156-0

I wonder if we should also take a look at clarithromycin as it has an even greater effect on IL-6 than Azithromycin. At least that is what I remember reading a long time ago.


https://www.vox.com/2020/3/12/21176...eaths-china-treatment-cytokine-storm-syndrome

That and myocarditis. Check this article from a patient in January. It doesn't say where this happened but all 4 authors are Chinese. It also doesn't say Covid-19 positive but the picture painted sure says that.

https://www.acc.org/latest-in-cardi...12/00/coronavirus-fulminant-myocarditis-saved

 

[Proud NJ Sports Fan]

https://www.nj.com/coronavirus/2020...eatment-is-being-fast-tracked-by-rutgers.html

 

[CERU00]

Latest tweet from Gov Murphy. Unfortunately, NJ's projected peak looks to be greater than originally thought, peaking at near 100 deaths per day in 5 days; problem is there were 200 deaths in NJ yesterday, so not sure what to make of it.

View embedded media

I'm sure all it takes is a couple non-conforming populations like Lakewood to really skew the results..

 

[RU848789]

I'm sure all it takes is a couple non-conforming populations like Lakewood to really skew the results..

Yep, that and a couple of nursing homes being ripped through with deaths...

 

[bac2therac]

so hearing some stuff that the baby that died in CT may have not died from coronavirus but something else...tested positive for it but not the cause of death....if true, its very important people get this right, the Gov of CT quickly was tweeting the death of this infant out. Cannot confuse the public