Novel Coronavirus and Better Unsafe than Sorry
It is possible that a known pharmaceutical called remdesivir inhibits the reproduction of the Covid-19 coronavirus. It inhibits (some) RNA dependendent RNA Polymerases — the type of enzyme the virus uses to replicated its genome and express its genes. It is known that it is a potent inhibitor of the RNA dependendent RNA Polymerases used by the MERS coronavirus
update: here is a good site for Covid-19 data.
So what will be done with remdesivir ? What should be done ? Is what will be done anything like what should be done ?
I think I can guess what will be done. Different groups will work on different projects. Some labs will attempt to produce and purify the Covid-19 RNA dependent RNA polymerase to check if remdesivir inhibits it too. The patent holder, Giliad Science will start a two Phase III trials of remdesivir. Results will be reported and then the FDA will decide whether to approve it for use.
This is good as far as it goes, but I don’t think it goes close to far enough.
I think that aside from the trials, Remdesivir should be given to patients and contacts of patients. It is known to be safe (from the trial which shows that it doesn’t cure Ebola). Also a whole lot of it should be produced starting a month ago.
The first proposal implies changing the law — making an exception to the Food and Drug Act. It also requires some organization without shareholders to bear the liability for side effects (The bill should make the US Federal Government liable). It goes completely against the standard logic that it is against patients’ interests to treat them with unproven drugs. There are two reasons to abandon that logic. First it is unconvincing in general. Second the risk of reacting too slowly to a budding pandemic is huge.
The mass production of Remdesivir is a simpler decision. The risk is a high chance of wasting tens or hundreds of millions of dollars. The risk of business as usual is a small chance of tens of millions of deaths, because drug shortages prevent effective control of the epidemic.
The logic of regulation and policy is first do no harm and better safe than sorry. Safety is not currently possible. A small c conservative approach is also small c crazy.
update:
Ah a vaccine. Yes a candidate vaccine will exist soon. Also it will be available to actually vaccinate people in a year or two. The delay will be do to required tests of safety and effectiveness and then the time it takes to ramp up production. These problems are much worse for a vaccine than for Remdesivir. Remdesivir is known to be safe, so clinical trials have begun. It will soon be known if it works.
Standard safety testing of a candidate vaccine takes a long time. Effectivness testing takes a while. Ramping up production takes a long while. Consider Ebola. Candidate vaccines already existed in 2013. A vaccine was approved by the FDA Dec 19, 2019 It was used starting in 2018 in the Democratic Republic of the Congo.
Does not look this way. In China epidemic is almost over with mortality between 2 and 3%.
Cases in other countries has mortality on 0.1% much like for a regular flu.
I think chances of infection of a billion people are non-existent.
Trump might have a point that spring can help — coronaroviruses worst period of spreading is winter (although there are exceptions)
As the virus is very similar (I think 80% of genome) to chicken flu the creation of vaccine is possible. Israeli scientists clain that ‘In a few weeks, we will have coronavirus vaccine’
https://www.jpost.com/HEALTH-SCIENCE/Israeli-scientists-In-three-weeks-we-will-have-coronavirus-vaccine-619101/
I think the danger of the pandemic was exaggerated. In no way this is a new Spanish flu. Not even close.
Which means chances of tens million of more death are very exaggerated, highly unrealistic estimate.
lol, Trump lovers coming out of the word work to support
There is no basis for the 0.1% death rate outside of China assertion. The ratio of deaths to cases is greater than that and many people are in serious or critical condition. The death rate is not statistically signficantly higher in China than in other countries. https://www.worldometers.info/coronavirus/
Other countries have neither the public health competence nor the ruthlessness of China (I am thinking mostly of other developing countries but the USA does seem to have problems with testing kits).
A candidate vaccine will be available soon. It will not be proven safe and effective and then mass produced soon. The argument that it is better to consider costs and benefits and not stick to the rule that first second and third do no harm applies to vaccines much more than to remdesivir (known to be safe can be quickly tested for effectiveness).
All experts agree that a vaccine will be available in a year or two. They know that candidate vaccines will exist soon. They know that the problem is proving safety and effectiveness and then producing a lot. A vaccine could be available in much less than a year. It would be used well within a year if people listened to me. But they won’t.
It probably won’t be like the Spanish Flu, because of vigorous quarantine type counter measures. A vaccine will help, but could be too late for tens of millions. Remdesivir will probably work and this will be proven fairly soon. I will probably make a difference. It could make a larger difference.
Robert:
I believe the 21st Century Cures Act would cover this issue. A brief comment: “The law builds on FDA’s ongoing work to incorporate the perspectives of patients into the development of drugs, biological products, and devices in FDA’s decision-making process. Cures enhances our ability to modernize clinical trial designs, including the use of real-world evidence, and clinical outcome assessments, which will speed the development and review of novel medical products, including medical countermeasures. https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/21st-century-cures-act
Additional information from TPM; “China’s aggressive measures have slowed the coronavirus. They may not work in other countries” Having worked with the Chinese for years, I tend to believe Erik. You may know them; but, you never know everything.
All commenters: please note that official numbers from China are almost certainly inaccurate, both in numerator and denominator.
The total number of cases diagnosed is limited by test kits, which have recently moved from 300 kits manufactured per day to 4000 kits/day. Which is still at least an order of magnitude lower than the number of known cases. And anecdotal data coming from Chinese physicians and health workers indicates both a higher patient population than official, and many deaths not attributed to Covid (an epidemic of “pneumonia” deaths in Wuhan preceding the announcement of Covid, for example). Much is being hidden – not from us, they don’t care about us; they’re hiding the information from their own people, which they do as a general policy on most subjects.
Which is all mostly to say, treat the official Chinese numbers as unreliable, with large error bars in unpredictable directions. Look to South Korea and Singapore for reliable data; both are actively and aggressively testing, and both are strong open information societies.
Erik:
Welcome to Angry Bear. Your comment went to moderation first (just approved it). It goes to moderation first to weed out spam, spammers, and advertising. Nice comment by-the-way. Thank you.
> There is no basis for the 0.1% death rate outside of China assertion
Low mortality rate for COVID-19 is masked by high (15%) mortality rate of person over 80.
For people younger then 40 it is a reasonable assertion as death concentrate on age group starting from 50-59age group. Men are approx. twice susceptible then women.
Per country currently the worst in 4.4% (Iran.) With 8,000-Plus Deaths in U.S. Alone, Flu Far More Deadly Than Coronavirus
See https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6
The most cruel experiment with the Diamond Princess cruise ship (close space, high level of contact between passengers, lack of qualified medical personnel and supplied, etc)
Six people died and 700 people were infected out of 3700. For all other the immune system managed to kill the virus. Which suggests susceptibility rate of around 20%.
It suggest 0.2% mortality and the around 20% population are susceptible for the virus. For 80% the immune system proved to be strong enough to kill the virus.
Two Japanese passengers – an 87-year-old man and an 84-year-old woman – were the first to die from the disease on February 19.
In the USA out six deaths at least four have been among residents of a long-term care facility called Life Care Center, where more than 50 residents and staff members have shown symptoms of the virus.
Only 14% of cases are more severe then a regular flu:
I believe you hypothetic about the possibility of the pandemic with high mortality rate is without merit.
We do not need to contribute to the panic, which already started in the USA with population buying masks, isopropyl alcohol and hand sanitizers as if there no tomorrow (a friend told me that bottle of hand sanitizer on Amazon today in $60 or so ;-).
And masks are effective mostly for sick people (block spreading of infected aerosol from lungs) , mush less for healthy people as they do no follow proper decontamination procedures anyway.
BTW in China epidemics is already subsiding. Ass for severity only 14 percent of cases are severe (which means more server than a regular flu):
Likbez:
On the one hand, I think that you are right to suggest that we shouldn’t run around in a panic. However, it seems like people have only two settings. It will ruin the whole world and no big deal.
A case fatality rate of 2% is nothing to sneeze at. If the flu had that mortality rate, we’d be looking at between 100k and 1mil people dying every year just here in the US. The fact that most of them would be >60 years old is cold comfort. btw, a confidence interval for 7 deaths out of 700 infected includes 2%.
Though I wouldn’t be too confident with your 20% susceptibility calculation, the spread has been slower than I would have thought given the initial 2-3 R0 estimates. Part of this has been the absolutely herculean effort that the Chinese people have undertaken to contain it’s spread, but maybe there is more.
That said, the number of identified non-Chinese cases looks to be doubling every two weeks or so. That’ll be a big deal soon unless we can bend the curve through large scale action like in China, or the dynamics change as the weather gets warmer (sorry southern hemisphere…).
I will be curious to see how this compares to the Spanish flu once we’ve had time to reflect on it. We live in a much more connected world now, but have vast advantages. How quickly would covid-19 spread if we were in a world war, didn’t have a global epidemiological core at the ready, and were actively hiding its existence? What would be the case fatality rate without ICUs and our modern medical infrastructure?
Ian:
Welcome to Angry Bear. First time comments and commenters always go to moderation to weed out spam, spammers, and advertising. Nice comment, thank you.
Gilead Sciences is running phase III trials for a treatment per one of the links. This company 20 years ago did quite well selling an HIV treatment. And of course they were first to market with a treatment for Hep C which cost a mere $1000 per day for an 84 day treatment. So many profits, so little time. I wonder what they will charge if this COVID-19 treatment pans out.
Ian Fellows,
Yes, you made reasonable corrections/clarifications. Thank you !
I agree then 20% susceptibility is probably too optimistic. It is interesting that susceptibility of medical personal exposed to patients in Wuhan is over 50%. And that are people with well trained immune system.
So my 20% figure is definitely suspect.
At the same time doubling each two weeks for the initial stages of epidemic is what you can expect in any flu epidemics.
The situation in the USA complicated by the fact the people are pushed coming to work even with slight flu symptoms.
Also healthcare is weakened by neoliberal healthcare and dominance of the private equity sharks in emergency rooms.
For all practical purposes I would classify the situation in the USA as similar to the situations in the third world countries. And that will increase the cost and duration of the epidemic considerably.
Much depends on availability of a reliable and free test. Currently the test cost money and that greatly complicates the situation in the USA increasing the number of infections and prolonging its duration. Probably considerably unless God and spring help us.
Last week, the Miami Herald reported that Osmel Martinez Azcue “received a notice from his insurance company about a claim for $3,270” after he visited a local hospital fearing that he contracted coronavirus during a work trip to China.
If test cost money, that will also help to kill more old and infirm (“disaster capitalism” in action). which could be saved if intervention come on easily stages of the disease (this is just a virus pneumonia after all)
And the private equity sharks with their exorbitant ambulance and emergency room changes need to be put in place and limited to what Medicare pays.
So hopefully Congress will provide emergency funding for that. We are wasting so much money of homeland security that I would take those money from them.
Fighting panic and fearmongering
1. The World Bank announced Tuesday afternoon that it would fund an initial $12 billion in financing to combat the Covid-19 outbreak that is threatening to plunge the global economy into recession
An excellent, if technical video from 27 Feb. The speaker is a HK Chinese (English speaking) Epidemiologist.
Nowcasting COVID-19 for public health control: learning from the Chinese experience for global preparedness by Gabriel Leung
Angry Bear March 2 2020. Washington post March 11 2020
https://www.washingtonpost.com/business/economy/the-best-hope-for-coronavirus-treatment-is-an-experimental-drug-that-fizzled-against-ebola/2020/03/10/8a9e8cd4-5fe8-11ea-b29b-9db42f7803a7_story.html
You read it here first
Robert:
Have you read the latest “The Atlantic?”
The authors, who are medical doctors, then deduce a set of concrete recommendations for how to manage these impossible choices, including this: “It may become necessary to establish an age limit for access to intensive care.”
Those who are too old to have a high likelihood of recovery, or who have too low a number of “life-years” left even if they should survive, will be left to die. This sounds cruel, but the alternative, the document argues, is no better. “In case of a total saturation of resources, maintaining the criterion of ‘first come, first served’ would amount to a decision to exclude late-arriving patients from access to intensive care.”
In addition to age, doctors and nurses are also told to take a patient’s overall state of health into account: “The presence of comorbidities needs to be carefully evaluated.” This is in part because early studies of the virus seem to suggest that patients with serious preexisting health conditions are significantly more likely to die. But it is also because patients in a worse state of overall health could require a greater share of scarce resources to survive: “What might be a relatively short treatment course in healthier people could be longer and more resource-consuming in the case of older or more fragile patients.”
The Extraordinary Decisions Facing Italian Doctors
By the way, congrats on your being prescient in your posting. Usually, I catch up with it later.