PlagueWatch 2020-23 - Coronavirus

[bedeviled]

Dr. Denison (the guy I mentioned earlier) has two newer antivirals currently in testing: EIDD-1931 and EIDD-2801. Both compounds have in vitro activity against a wide variety of coronaviruses without any resistance found, including SARS-CoV. The second of these compounds is orally bioavailable and was very active against SARS in a mouse model

For clarity purposes: IIRC, EIDD-1931 & EIDD-2801 are actually the same drug. EIDD-2801 is, as you say, the oral formulation. Denison & Vandy are testing the compounds, but they were developed at Emory, hence the nomenclature which is short for Emory Institute of Drug Development

ETA: Emory news release about EIDD-2801.
Another Emory news release with the following info:

EIDD-2801 is an orally available form of the antiviral compound EIDD-1931; it can be taken as a pill and can be properly absorbed to travel to the lungs.

Statement that suggests it might be used in prophylaxis:

The results of the team’s most recent study were published online April 6 in the journal Science Translational Medicine. The new paper includes data from cultured human lung cells infected with SARS-CoV-2, as well as mice infected with the related coronaviruses SARS-CoV and MERS-CoV.
The study found that, when used as a prophylactic, EIDD-2801 can prevent severe lung injury in infected mice.

And another interesting characteristic:

Viruses that carry remdesivir resistance mutations are actually more susceptible to EIDD-1931 and vice versa, suggesting that the two drugs could be combined for greater efficacy and to prevent the emergence of resistance

[rsvman]

For clarity purposes: IIRC, EIDD-1931 & EIDD-2801 are actually the same drug. EIDD-2801 is, as you say, the oral formulation. Denison & Vandy are testing the compounds, but they were developed at Emory, hence the nomenclature which is short for Emory Institute of Drug Development

Thanks for this clarification. I wasn't sure whether 2801 was just an orally bioavailable form of the drug or whether the compound was slightly different.

[Jeffrey]

Speaking of pricing, I can only note that Martin Shkreli wants to be released from prison so that he can "help fight the Covid 19 virus."

Great, a human-sized rat available for testing.

[MChambers]

Texas becomes the first state to announcing a loosening of restrictions:

Gov. Greg Abbott on Friday announced initial steps to begin the process of reopening the Texas economy during the coronavirus pandemic, including those that in the next week will loosen surgery restrictions at medical facilities, allow all retail stores to provide product pickups and reopen state parks.

Abbott also named a "statewide strike force" devoted to getting the economy going again. Austin banker James Huffines will chair the task force, while veteran lobbyist Mike Toomey will be its chief operating officer. The group will oversee what Abbott described as a phased reopening.

https://www.texastribune.org/2020/04...t-coronavirus/

And this gives me a reason/excuse to post a Ray Wylie Hubbard tune:

[CDu]

Texas becomes the first state to announcing a loosening of restrictions:

Gov. Greg Abbott on Friday announced initial steps to begin the process of reopening the Texas economy during the coronavirus pandemic, including those that in the next week will loosen surgery restrictions at medical facilities, allow all retail stores to provide product pickups and reopen state parks.

Abbott also named a "statewide strike force" devoted to getting the economy going again. Austin banker James Huffines will chair the task force, while veteran lobbyist Mike Toomey will be its chief operating officer. The group will oversee what Abbott described as a phased reopening.

https://www.texastribune.org/2020/04...t-coronavirus/

And this gives me a reason/excuse to post a Ray Wylie Hubbard tune:

Interesting, as I am quite sure that Texas is not at the 14-days of decline phase yet.

[bundabergdevil]

Interesting, as I am quite sure that Texas is not at the 14-days of decline phase yet.

Yeah. It seems inevitable that new hot spot spikes are going to occur as some folks interpret phrase re-openings as all clear. There have already been reports of rural hot spots in areas without stay-at-home order.

It's tough for me to fully understand the mindset of the protesters chanting "lock her up" in Michigan but, then again, I have some at-risk people in my life and I'm very worried about their situations even while being empathetic to the other folks in my life who are economic casualties.

[Jeffrey]

Maybe, I'm just waiting for a miracle. Do you think 50 fold could be true for all of the USA?

“Our findings suggest that there is somewhere between 50- and 80-fold more infections in our county than what’s known by the number of cases than are reported by our department of public health," Dr. Eran Bendavid, the associate professor of medicine at Stanford University who led the study, said in an interview with ABC News' Diane Sawyer.

https://abcnews.go.com/Health/antibo...ry?id=70206121

[camion]

Maybe, I'm just waiting for a miracle. Do you think 50 fold could be true for all of the USA?

“Our findings suggest that there is somewhere between 50- and 80-fold more infections in our county than what’s known by the number of cases than are reported by our department of public health," Dr. Eran Bendavid, the associate professor of medicine at Stanford University who led the study, said in an interview with ABC News' Diane Sawyer.

https://abcnews.go.com/Health/antibo...ry?id=70206121

Going with round numbers, we currently have about 700,000 confirmed cases (Johns Hopkins numbers). 50 times that would be 35 million, around 10% of the U.S population. Seems high to me right now. I think we could top that in the coming months though.

[CDu]

Maybe, I'm just waiting for a miracle. Do you think 50 fold could be true for all of the USA?

“Our findings suggest that there is somewhere between 50- and 80-fold more infections in our county than what’s known by the number of cases than are reported by our department of public health," Dr. Eran Bendavid, the associate professor of medicine at Stanford University who led the study, said in an interview with ABC News' Diane Sawyer.

https://abcnews.go.com/Health/antibo...ry?id=70206121

Honestly? I'm not even sure it's true for the total population from which they sampled. It may be, but we don't know. As noted in the article, this wasn't a truly random sample of the population. It was a study driven by an online ad to submit to a blood test. That's likely to lead to selection bias upwards (i.e., overestimating the "true" infection rate).

There are other studies going on at the moment that may provide better information. I believe a study of MLB employees is ongoing. That would give a more truly random sample, and it would give a better idea of the national data. Additionally, if these researchers would include in the survey whether or not the person had been previously confirmed as infected, that would be a more reliable set of data. Because what we need to know is how that sample truly relates to the county at large before estimating the degree of unerreporting.

Regardless, even at face value their findings aren't overly thrilling either - it suggests that only around 5% of the US population has been infected (per the lead author). That's not great news from the idea of getting control of this thing. As we've discussed, we wouldn't be approaching herd immunity benefit at that low a level of immunity (even assuming all those individuals are now immune).

[Jeffrey]

Regardless, even at face value their findings aren't overly thrilling either - it suggests that only around 5% of the US population has been infected (per the lead author). That's not great news from the idea of getting control of this thing. As we've discussed, we wouldn't be approaching herd immunity benefit at that low a level of immunity (even assuming all those individuals are now immune).

I think 5% is a substantial improvement from a mortality perspective. If 16.5 million Americans are currently infected and 60,000 die, then doesn't that mean our true mortality rate is about 0.36%? That sounds a lot better than the numbers I've read and it would decrease substantially if any treatments materialize.

[CDu]

Going with round numbers, we currently have about 700,000 confirmed cases (Johns Hopkins numbers). 50 times that would be 35 million, around 10% of the U.S population. Seems high to me right now. I think we could top that in the coming months though.

Also, worth noting that California has one of the lower test rates in the country, ahead of only Kansas and Puerto Rico. So it may well be that they are wildly underestimating the number of cases in California (well, to be clear , I'm quite sure they are wildly underestimating the cases in California; the question is only by how much). But almost certainly less true nationally. For example, in states where the testing has been double that of California (or 4 times that), it's hard to believe that they are undercounting by anywhere near that degree. New York, for example, has tested 2.8% of the population. It seems entirely infeasible for their infection rate to be underestimated by 50-fold.

My guess is that there is some amount of selection bias into the survey going on (people who think they might have gotten it are more likely to submit to a voluntary survey like this), as well as some amount of "California is testing way less than most states" going on, both of which would lead to overstating the degree of national underreporting of data based on these results.

[CDu]

I think 5% is a substantial improvement from a mortality perspective. If 16.5 million Americans are currently infected and 60,000 die, then doesn't that mean our true mortality rate is about 0.36%? That sounds a lot better than the numbers I've read and it would decrease substantially if any treatments materialize.

A few things.

One, the case fatality rate is almost certainly not the ~5% we see in terms of deaths/cases. Most research I've seen suggests somewhere between 0.6% and 1.5%, so 0.36% wouldn't be that far off. The problem is that we don't have any immunity to this virus, so even a 0.36% mortality rate would mean a LOT more deaths are coming. That's roughly four times more deadly than the flu, and unlike the flu we have no inherent immunity (no vaccine, no prior infections) to help contain the disease. So without anything limiting the spread of infection other than new infections, there's nothing to stop that 5% from becoming, say 50% (or more). And since we're sitting at ~35000 deaths, you'd be talking about over 300,000 deaths in that scenario.

Two, that's assuming that the study is roughly representative of the national population. As noted, there are a few concerns here (selection bias to the survey and California's undertesting). It's probably not true that 2-4% of that county have been infected, and it's probably not true that the ratio of infected to confirmed profiles similarly nationwide given the differences in testing rates.

Three, we still don't appear to be THAT close to a treatment. There is certainly optimism for remdesivir (and maybe others), but probably still months away from its widespread availability even if it works.

[MChambers]

Also, worth noting that California has one of the lower test rates in the country, ahead of only Kansas and Puerto Rico. So it may well be that they are wildly underestimating the number of cases in California (well, to be clear , I'm quite sure they are wildly underestimating the cases in California; the question is only by how much). But almost certainly less true nationally. For example, in states where the testing has been double that of California (or 4 times that), it's hard to believe that they are undercounting by anywhere near that degree. New York, for example, has tested 2.8% of the population. It seems entirely infeasible for their infection rate to be underestimated by 50-fold.

My guess is that there is some amount of selection bias into the survey going on (people who think they might have gotten it are more likely to submit to a voluntary survey like this), as well as some amount of "California is testing way less than most states" going on, both of which would lead to overstating the degree of national underreporting of data based on these results.

Here's a study in Santa Clara, not peer reviewed, finding:

Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases. Conclusions The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases.

https://www.medrxiv.org/content/10.1...8GiP9ed5hlOm3I

Edit: I guess this is the study underling Jeffrey's post. I don't see it as good news, even if it is right.

[CDu]

Here's a study in Santa Clara, not peer reviewed, finding:

Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases. Conclusions The population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection is much more widespread than indicated by the number of confirmed cases.

https://www.medrxiv.org/content/10.1...8GiP9ed5hlOm3I

That is the same study we are talking about.

[OldPhiKap]

^^ if true, would that indicate:

1. You are much more likely to come in contact with an infected person and/or to become infected than you think; but
2. It has a much lower mortality and hospitalization rate than you think?

[CDu]

^^ if true, would that indicate:

1. You are much more likely to come in contact with an infected person than you think; but
2. It has a much lower mortality and hospitalization rate than you think?

Loosely yes. But as noted, that study has some serious limitations, both in terms of potential bias and generalizability.

But basically, in the best case that study suggests we are looking at a virus that is more deadly than flu if you get it, but for which we have no immunity and which has only hit about 5% of the population so far. In the worst case, it is 10-15 times more deadly than the flu and less than 1% have gotten it.

Basically, in either scenario we REALLY need to contain the disease until we get an effective and available treatment.

[Jeffrey]

One, the case fatality rate is almost certainly not the ~5% we see in terms of deaths/cases. Most research I've seen suggests somewhere between 0.6% and 1.5%, so 0.36% wouldn't be that far off. The problem is that we don't have any immunity to this virus, so even a 0.36% mortality rate would mean a LOT more deaths are coming. That's roughly four times more deadly than the flu, and unlike the flu we have no inherent immunity (no vaccine, no prior infections) to help contain the disease. So without anything limiting the spread of infection other than new infections, there's nothing to stop that 5% from becoming, say 50% (or more). And since we're sitting at ~35000 deaths, you'd be talking about over 300,000 deaths in that scenario.

Thanks, CDu, I completely agree!

I hope the USA does everything possible to limit deaths! I’m merely more comfortable with 300k being worst case scenario as opposed to the 1-3 million estimates I originally saw.

I’ve closed my business to the public and will keep it closed for as long as I legally can. Afterwards, I hope I can legally require all customers and employees to wear masks.

[CDu]

Thanks, CDu, I completely agree!

I hope the USA does everything possible to limit deaths! I’m merely more comfortable with 300k being worst case scenario as opposed to the 1-3 million estimates I originally saw.

I’ve closed my business to the public and will keep it closed for as long as I legally can. Afterwards, I hope I can legally require all customers and employees to wear masks.

Just to be clear, 300K is probably not the worst case. Worst case is still over 1 million (if the death rate is around 1-1.5% instead of the 0.3% and assuming restrictions are relaxed too soon). If 30% get it and the death rate is 1%, that is 1 million deaths.

[PackMan97]

Also, worth noting that California has one of the lower test rates in the country, ahead of only Kansas and Puerto Rico. So it may well be that they are wildly underestimating the number of cases in California (well, to be clear , I'm quite sure they are wildly underestimating the cases in California; the question is only by how much).

If California were way behind on testing the cases would be showing up at the hospital. They aren't. Therefore, it's fairly safe to assume, like NC they have a good handle on things even with the low testing.

[fisheyes]

A report from the Boston Globe regarding Chelsea which seems to be a hot bed of infection.

https://www.bostonglobe.com/2020/04/...e-coronavirus/

This report found that 32% of people who had not tested positive for COVID 19 had antibodies.

The pilot study was done by MGH researchers who set up shop in a town square in Chelsea and took samples from 200 "random"? people on the street. Those who had tested positive using the swab technique were excluded.

"The 200 participants generally appeared healthy, but about half told the doctors they had had at least one symptom of COVID-19 in the past four weeks. Public health experts already knew Chelsea had the state’s highest rate of confirmed COVID-19 cases and that the actual rate was probably higher. At least 39 residents have died from the virus, and 712 had tested positive as of Tuesday, a rate of about 1,900 cases per 100,000 residents, or almost 2 percent."

I doubt this is reflective of other areas in the country, but 32% is way closer to herd immunity (>70%) than other reports. Trying to look at the positives here.