COVID-19 Coronavirus Containment Efforts

[DennisN]

It looks like it will be very difficult to estimate the overall death toll. China's numbers have been discussed, that New York and Italy are missing some cases has been discussed, but it looks like it's even worse in some other countries.

Speaking of that I recently read two articles from a couple of weeks ago:

http://edition.cnn.com/2020/03/24/americas/coronavirus-latin-america-presidents-intl/index.html
(CNN, March 25, 2020)

http://www.bbc.com/news/world-latin-america-52080830
(BBC, 29 March 2020)

I also read another interesting article about leaders in apparent denial during this crisis, but regretfully I can't find it at the moment. Denial is a powerful but also sometimes dangerous psychological defense mechanism...

Furthermore, I am not updated about the current situation in Brazil, Mexico and Nicaragua which were the countries mentioned in the articles above.

 

[DennisN]

Some more bad news.
https://www.scmp.com/news/china/soc...uld-target-immune-system-targeting-protective

That was a quite disturbing read...

 

[kyphysics]

That was a quite disturbing read...

Here was one quote from the piece I didn't understand:

The gene behind the fusion function in Sars-CoV-2 was not found in other coronaviruses in human or animals.

But some deadly human viruses such as Aids and Ebola have similar sequences, prompting speculation that the novel Coronavirus might have been spreading quietly in human societies for a long time before causing this pandemic.

How are they extrapolating that this novel Coronavirus may have been spreading among humans "for a long time"?

 

[Jarvis323]

Sorry, here's one of the papers.
https://www.nature.com/articles/s41423-020-0424-9

 

[DennisN]

Here was one quote from the piece I didn't understand:

The gene behind the fusion function in Sars-CoV-2 was not found in other coronaviruses in human or animals.

But some deadly human viruses such as Aids and Ebola have similar sequences, prompting speculation that the novel Coronavirus might have been spreading quietly in human societies for a long time before causing this pandemic.

How are they extrapolating that this novel Coronavirus may have been spreading among humans "for a long time"?

I don't know. It seems they might be comparing with the history of Aids and Ebola. But there may be additional reasons for the speculation, I really don't know.
I am way out of my comfort zone here, biology/virology is definitely not my strong side.
Maybe some other more knowledgeable thread participants could offer some perspective...

 

[DennisN]

Some more bad news.
https://www.scmp.com/news/china/soc...uld-target-immune-system-targeting-protective

When I read that article on South China Morning Post (which is a Hong Kong newspaper) there was another article there that caught my attention:

• Coronavirus that causes Covid-19 can produce more than three times as many pathogens than Sars strain, HKU study reveals (SCMP, 11 Apr, 2020)

Four quotes:

“In some cases, Sars-CoV-2 could replicate by about 100 times within 48 hours, while the Sars virus may have peaked at about 10 to 20 times of replications,” Dr Chu Hin, research assistant professor from HKU’s medical school, said.

[...]

It took about six months to contain the Sars epidemic.
But it is a much bigger challenge for the Covid-19 pandemic, which has infected more than 1.6 million people around the world and caused more than 100,000 deaths in four months. According to the World Health Organisation, some 8,098 people were infected by Sars and 774 died of it.

[...]

“There is almost no possibility of containing the virus before July,” said Yuen, of the University of Hong Kong (HKU), who led the study published in scientific journal Clinical Infectious Diseases.

[...]

"The virus is like a ninja, replicating inside the body with lower interferons and inflammatory response"
- Jasper Chan, clinical assistant professor, University of Hong Kong medical school

 

[kyphysics]

Possible treatment: Head lice drug killed COVID-19 virus in less than 48 hours during lab test

https://abc11.com/coronavirus-treatment-head-lice-drug-kills-ivermectin-covid/6102085/

The latest lead for researchers is an anti-parasitic drug called ivermectin, which is often used to treat head lice.

According to ABC News, one early study showed ivermectin can kill the virus that causes COVID-19 in 24 to 48 hours.

"Finding a safe, affordable, readily available therapy like ivermectin if it proves effective with rigorous evaluation has the potential to save countless lives," said Dr. Nirav Shah, an infectious disease expert with the NorthShore University HealthSystem.

The study was only a first step. It only showed that the drug could kill the virus in a laboratory setting (in vitro). It is still entirely too early to know if that will translate into an effective treatment.

"There are numerous examples of drugs with in vitro activity not proving effective in human studies," Shah said. . .

Ivermectin was developed back in the 1970-80s. It is an anti-parasitic treatment that was first used to treat nematodes in cattle, then to combat river blindness in humans. It's most recently been used as a topical treatment against head lice.

COVID-19 is not a parasite, but investigators said ivermectin treats it like one--blocking the viral RNA from invading healthy cells. With it unable to enter the cell, the RNA is slowed from replicating, giving the patient's immune system more time to fight it off.

Yet another possible treatment. Let's all continue to hope one or MORE of these works!

 

[Ygggdrasil]

It is likely that the virus is zoonotically transmitted from bats to humans. But since there are no bats sold in the Wuhan market, and that bats are not naturally found near the market, and that the lab is using live bats for research, which are the claims of the other study, it is possible that the real place of first infection are the labs, where the virus infected a lab worker, and not the market.

Are you claiming that the virus was transmitted directly from bats to humans? On what scientific basis do you make that claim?

Sorry, here's one of the papers.
https://www.nature.com/articles/s41423-020-0424-9

I'm not a expert in the area, but one concern I have about the article is that they did not actually study the SARS-CoV-2 virus. Rather, they pseudotyped HIV (a virus known to infect T-cells) with the spike protein from SARS-CoV-2 virus. I don't have experience with these types of experiments, but is it possible that their findings are an artefact of using pseudotyped lentiviruses?

The authors do note that individuals infected with COVID-19 exhibit lymphocytopenia (low white blood cell counts), but acute lymphocytopenia can be caused by other viral infections, such as influenza, hepatitis and even the common cold (though some common colds are caused by other strains of coronavirus).

Here was one quote from the piece I didn't understand:

The gene behind the fusion function in Sars-CoV-2 was not found in other coronaviruses in human or animals.

But some deadly human viruses such as Aids and Ebola have similar sequences, prompting speculation that the novel Coronavirus might have been spreading quietly in human societies for a long time before causing this pandemic.

How are they extrapolating that this novel Coronavirus may have been spreading among humans "for a long time"?

I first read the paper published in Molecular and Cellular Immunology being reported on by the SCMP article, then the SCMP article, and it's pretty clear that the person writing the SCMP article doesn't really understand the science. The explanations of the paper are mostly ok, especially when guided by quotes from the paper or the authors, but explanations of issues outside of the paper are confusing at best. I will note that the bolded statements do not appear in the published paper (indeed, the published scientific paper does not mention HIV, AIDS or ebola).

My guess about what the article is talking about is the presence of a functional polybasic furin cleavage site in the spike protein of the virus. This site allows the protein to be cleaved in half by furin proteases found widely throughout the human body on the outside of cells (including the respiratory tract). Furin-mediated cleavage of the spike protein could facilitate entry of the virus into cells. See this paper from Nature Medicine or this article from the Atlantic for technical or simpler explanations of these features, respectively. Proteins from HIV and Ebola also contain furin cleavage sites as do many human proteins (the furin protease recognises a fairly simple motif requiring the proximity of two arginine amino acids in an extracellular portion of the protein), so I don't think the presence of a furin cleavage site implies any relationship to these viruses. However, I don't know why the author of the SCMP piece claims this feature is unique: the MERS Coronavirus that infects humans as well as MERS-like coronaviruses found in bats also contain these features.

The origin of the furin cleavage site in SARS-CoV-2 is unknown. Although we have found spike proteins from animal coronaviruses that closely resemble the SARS-CoV-2 spike protein, these lack the furin cleavage site. These findings offer two possible explanations (discussed further in the Nature Medicine article): 1) evolution of the site in an animal host (because we have very few Coronavirus sequences from animals, we could very likely have missed the "missing link" between animal coronaviruses and the current SARS-CoV-2 virus behind the COVID-19 outbreak) or 2) evolution of the site in humans (which would suggest that the virus may have been transmitting in humans long before the current outbreak). While possibility #2 is unlikely (genetic studies of the virus suggest a relatively recent origin ~late Nov 2019 to early Dec 2019), it can't completely be ruled out yet. Potentially, studies of banked samples from the Wuhan region (especially those looking for antibodies against SARS-CoV-2 in blood samples pre-dating the outbreak) could help resolve this question.

 

[Ygggdrasil]

Possible treatment: Head lice drug killed COVID-19 virus in less than 48 hours during lab test

https://abc11.com/coronavirus-treatment-head-lice-drug-kills-ivermectin-covid/6102085/

Yet another possible treatment. Let's all continue to hope one or MORE of these works!

Does not look so promising to me. According to the paper (published in the journal Antiviral Research) that looks at the effects of ivermectin in cultured cell experiments, they needed a concentration of ~2.5µM to inhibit infection of cells. Studies of the pharmacokinetics of ivermectin show that, at typical doses of the drug administered to patients, concentrations in the blood reach only ~60nM, about 60x lower than the dose needed to see effect in cell culture experiments.

Relevant XKCD:

https://xkcd.com/1217/

 

[kadiot]

Are you prepared to do social distancing until a treatment or vaccine is found vs Covid19, i.e., year 2021 or 2022?

 

[kadiot]

IMF: Global recession, no country will escape the downturn this year.

"The US economy is expected to contract by 5.9% this year, representing the biggest annual decline since 1946. Unemployment in the US is also expected to jump to 10.4% this year."

 

[atyy]

IMF: Global recession, no country will escape the downturn this year.

China, India to narrowly avoid recession in COVID-19 stricken 2020: IMF
https://www.channelnewsasia.com/news/business/covid19-chinaindia-recession-imf-12641308
"India, Asia's third-biggest economy, is also expected to grow at 1.9 per cent in 2020 before surging 7.4 per cent next year.
Indonesia too is expected to just stay above water, gaining 0.5 per cent this year before an 8.2 per cent bounce in 2021.
However, more advanced economies in the region - Japan, South Korea, Australia, Singapore and Hong Kong - will dip into recession, according to the forecast.
Thailand and Malaysia are also expected to be in negative territory, but the Philippines and Vietnam are expected to still see modest growth this year."

 

[kyphysics]

I'm more pessimistic for unemployment and growth than those reports.

I think until we get a vaccine, even if you let people go out and work or play (no more shelter-in-place):

a.) a significant percentage of people will voluntarily keep sheltering (i.e., seniors, immuno-compromised, and the otherwise infirm)
b.) businesses like airlines, cruises, casinos, movie theaters, amusement parks, malls, concerts, buffet restaurants, etc. - anywhere with large gatherings of people - will likely see at least a 30% hit (if not more) for a while
c.) people's spending patterns will likely be drastically changed ...I think people will be more tight-pocketed for a few years after going through this scare

That will lead to a lot of businesses going under or hiring less.

 

[kyphysics]

Does not look so promising to me. According to the paper (published in the journal Antiviral Research) that looks at the effects of ivermectin in cultured cell experiments, they needed a concentration of ~2.5µM to inhibit infection of cells. Studies of the pharmacokinetics of ivermectin show that, at typical doses of the drug administered to patients, concentrations in the blood reach only ~60nM, about 60x lower than the dose needed to see effect in cell culture experiments.

Relevant XKCD:
View attachment 260653
https://xkcd.com/1217/

I'm guessing injecting bleach into my blood stream works as well by that logic?

 

[kyphysics]

I also don't know how CHina is listed as a country that will narrowly avoid recession.

Who is going to buy their exports?

 

[kadiot]

"... Philippines and Vietnam are expected to still see modest growth this year."

Interesting. I wonder what's the reason behind positive forecast for the Philippine economy.

 

[ChemAir]

I also don't know how CHina is listed as a country that will narrowly avoid recession.

Who is going to buy their exports?

Don't know. US has a record decrease in March retail sales, -8.7% rather than the predicted 8%. In April, with an entire month of lockdown rather than the two weeks that set a record in March, I expect worse this month.

Poverty, crime, and other downstream monetary issues may kill more than the virus we are trying to protect ourselves from.

Unfortunately, this seems to be as much a media/political issue as it is about public health.

States are taking in record low sales taxes while paying out record high unemployment, which is not sustainable. This country hasn't seen this before. I expect a very slow rise out of this, very slow.

 

[BillTre]

A Science news article titled "Ending Coronavirus lockdowns will be a dangerous process of trial and error" discusses issues involved in deciding when it is reasonable to life restrictions. Important are reducing the number of cases and reducing the effective reproductive number, R.
The article describes "three control knobs" for controlling Coronavirus spread:

1. isolating patients and tracing contacts
2. border restrictions
3. social distancing

Tracing contacts is labor intensive and probably not feasible if there are still large numbers of people infected (seems not currently feasible in US, they quote an estimate that the US would have to train about 100,000 people for tracing, I am thinking that phone app tracing won't happen too soon in the US due to privacy concerns, but?).

Robust testing with a quick turn-around would also be important in isolating patients and tracing contacts (seems not currently feasible in US).

These are things that (IMHO) should be dealt with before any great loosening of social distancing occurs.
Current lack of good data limits understanding on how different actions affect R and makes decisions more difficult.
In a large country like the US, local differences will probably be important (IMHO) in determining when it is an appropriate time to make changes.

In 2004, mathematician Jacco Wallinga of the Dutch National Institute for Public Health and the Environment and colleagues published a statistical method to estimate R in real time, which is now used around the world. Researchers are also incorporating data on mobility patterns and people’s behavior to make the estimates more accurate. Having real-time estimates of R is important, says Adam Kucharski, a modeler at LSHTM: “If governments put a measure in or lift it, they can get a sense of what the immediate implications are, rather than having to wait,” he says.

(too big for one screenshot)

 

[OmCheeto]

It's a few days behind now, but this presentation from UT Austin pointed to an interesting graph put together by Stephanie Jolly: https://www.wave3.com/2020/03/24/graph-comparing-ky-tenn-coronavirus-responses-goes-viral/

Up to March 22, the growth of cases in Kentucky is less than in Tennessee. This may be because Kentucky implemented social distancing measures earlier.

I gave up hope that "case counts" were in any way accurate a few days before you posted this, so I've been keeping track.

One would think that Tennessee, with the consistently higher case counts, would end up with the higher death rate. I'm not seeing it.

 

[wukunlin]

I also don't know how CHina is listed as a country that will narrowly avoid recession.

Who is going to buy their exports?

There are certain goods like electronics where you simply don't have a choice. Also the consumer market in China is probably large enough to sustain itself without relying on exports for growth.

 

[kyphysics]

Eeeeek. Singapore's new case rate has doubled from 200's to 400's.

Not good for the "model" nation in this outbreak.

 

[mfb]

Who is going to buy their exports?

Who isn't?
You think people will suddenly care where their products are from?

Worldwide confirmed deaths have stabilized at ~6000/day:

Source

2000 from the US, 600-700 from the UK, France, Italy and Spain each, ~200 from Germany, ~1500 elsewhere.
Caveat: This is missing many deaths, especially in the "elsewhere" category.

 

[atyy]

Eeeeek. Singapore's new case rate has doubled from 200's to 400's.

Not good for the "model" nation in this outbreak.

Perhaps that is from increased testing in the dorms (for construction workers). I think that has been difficult to manage as there hasn't been enough space for social distancing there. Hopefully it will get better as they find at least temporary living space for them in which social distancing is possible.

The health ministry has recently been plotting a new statistic called "community cases". The numbers are much higher than before the school holidays, but the number of new community cases per day has been pretty constant over the last two weeks. Take a look at the last column of the first table (Fig 1.1) in each of these reports, or the orange bar graph in the figure (Fig 1.2) after the table.
https://www.moh.gov.sg/docs/librari...ion-report/situation-report---15-apr-2020.pdf
https://www.moh.gov.sg/docs/librari...port/situation-report---13-apr-2020-2354h.pdf

 

[atyy]

Who isn't?
You think people will suddenly care where their products are from?

It's probably more that if there are recessions in Europe and the US, to which China exports, the demand for Chinese product from those regions will decrease a lot. That's probably already been factored into the IMF estimates, so it could be as @wukunlin said that they have a large domestic market.

 

[kyphysics]

It's probably more that if there are recessions in Europe and the US, to which China exports, the demand for Chinese product from those regions will decrease a lot. That's probably already been factored into the IMF estimates, so it could be as @wukunlin said that they have a large domestic market.

Yeah, the lack of demand from Europe and U.S. was of concern. But, I also don't trust China's domestic figures either. They cook their books - widely known they report fake GDP numbers all the time.

Although, if cooking the books works, then it works. It'll be interesting to see where their reported growth comes from.

 

[kyphysics]

Whatever China reports, I'd compare it with China Beige Book: https://www.chinabeigebook.com/

They are the largest and most trusted non-Chinese government sponsored source of economic data from China.

 

[kadiot]

This is an interesting comparison among ASEAN COVID-19 cases. Do you agree with this presentation?

 

[anorlunda]

Sweden is called an outlier because it has refused lockdown.

https://www.msn.com/en-us/news/world/swedish-virus-deaths-top-1000-fueling-criticism-over-strategy/ar-BB12C1xU

 

[Ygggdrasil]

This is an interesting comparison among ASEAN COVID-19 cases. Do you agree with this presentation?
View attachment 260743View attachment 260743

The number of total confirmed cases depends a lot on how much testing has been done. It would be more informative if presented along with the number of individuals tested.

 

[kadiot]

Postmortem is now on.

https://www.theatlantic.com/politic...ganization-blame-pandemic-coronavirus/609820/

 

[kadiot]

Sweden is called an outlier because it has refused lockdown.

https://www.msn.com/en-us/news/world/swedish-virus-deaths-top-1000-fueling-criticism-over-strategy/ar-BB12C1xU

View attachment 260744

EU has called on Sweden to revise their anti-Covid measures. I bet that if they don't change them, people coming into the EU from Sweden might be banned from entering EU or at the very least, asked to self-quarantine.

 

[Vanadium 50]

Sweden is called an outlier because it has refused lockdown.

I'm afraid that plot is innumerate nonsense.

You don't take 100 deaths/million and 50 deaths/million and add them to get 150 deaths/million. You just don't.

Second, those plots are cumulative. They, by construction, integrate out day-to-day effects. Sweden has a high death rate today, but it has since the beginning - since before anyone locked anything down.

Further, Sweden has a very high case fatality ratio, and has since the beginning. Picking "deaths" instead of "cases" to plot emphasizes this. One can argue the reasons this might be, but it emphasizes Sweden was an outlier since before anyone locked anything down.

So, what should they have used? I would suggests the fraction of deaths in the last 15 days compared to the total. If the whole point of a lockdown is to save lives, we should be seeing it save lives, no?

I picked 15 because it's easy to get off Wikipedia. But that's not a crazy number: 2-3 weeks since shutdoiwns began, and the disease has on average a 5-6 day incubation period, and a couple days for the disease to progress. That leaves time for one or two cycles. So what does the data say? Sweden is at 63%, Denmark 61%, Norway it's impossible to tell, and Germany (for comparison) is 71%.

Based on this data, it's hard to say lockdowns are doing anything at all. If you want to make a big deal of 61% vs 63%, that says a Swedish lockdown would have saved 24 people.

At this point, a lot of people are invested in the lockdown and see a Swedish failure as validation of their preferred policies. (And indeed, the ultimate source of that graph was from a news source whose owner has political ambitions) But if we want to to call ourselves scientists, we have to look at the evidence.

Oh, and did I say that plot is innumerate nonsense?

 

[anorlunda]

There's a lot of talk on the news about widespread testing as a prerequisite to ending the lockdown. But how is "widespread testing" defined? Dr. Fauci was asked about that yesterday, and his answer sounded evasive.

I also see a lack of specifics about scaling up testing capacity. How many kits in the USA, 10 million, 100 million, 330 million? Back end lab processing tests/day? Turnaround time? What criteria for who gets tested? Once someone tests negative, how long until a second test? Effciency of the testing program?

I would define efficiency as the ratio of $\frac{\text{infected people tested}}{\text{infected people}}$

Without answers to those questions, how could anyone predict when widespread testing will be ready or has been achieved?

 

[kadiot]

how could anyone predict when widespread testing will be ready or has been achieved?

Good question. And also, how effective were they in reality.

 

[kadiot]

Handguns, rifles? Perhaps they think they can kill Covid19 virus in a shoot out? They would be better off carrying disinfectant pistols/spray!

https://www.msn.com/en-gb/news/world/michigan-residents-armed-with-rifles-and-handguns-defy-stay-at-home-order/ar-BB12HeNs