Boris Is Back!

Boris Johnson's statement in full

I am sorry I have been away from my desk for much longer than I would have liked

and I want to thank everybody who has stepped up

in particular the First Secretary of State Dominic Raab

who has done a terrific job

but once again I want to thank you

the people of this country

for the sheer grit and guts

you have shown and are continuing to show

every day I know that this virus brings new sadness and mourning to households across the land

 and it is still true that this is the biggest single challenge this country has faced since the war

and I in no way minimise the continuing problems we face

and yet it is also true that we are making progress

with fewer hospital admissions

fewer covid patients in ICU

and real signs now that we are passing through the peak

and thanks to your forbearance, your good sense, your altruism, your spirit of community

thanks to our collective national resolve

we are on the brink of achieving that first clear mission

to prevent our national health service from being overwhelmed

in a way that tragically we have seen elsewhere

and that is how and why we are now beginning to turn the tide

If this virus were a physical assailant

an unexpected and invisible mugger

which I can tell you from personal experience it is

then this is the moment when we have begun together to wrestle it to the floor

and so it follows that this is the moment of opportunity

this is the moment when we can press home our advantage

it is also the moment of maximum risk

because I know that there will be many people looking now at our apparent success

and beginning to wonder whether now is the time to go easy on those social distancing measures

and I know how hard and how stressful it has been to give up

even temporarily

those ancient and basic freedoms

not seeing friends, not seeing loved ones

working from home, managing the kids

worrying about your job and your firm

so let me say directly also to British business

to the shopkeepers, to the entrepreneurs, to the hospitality sector

to everyone on whom our economy depends

I understand your impatience

I share your anxiety

And I know that without our private sector

without the drive and commitment of the wealth creators of this country

there will be no economy to speak of

there will be no cash to pay for our public services

no way of funding our NHS

and yes I can see the long term consequences of lock down as clearly as anyone

and so yes I entirely share your urgency

it’s the government’s urgency

and yet we must also recognise the risk of a second spike

the risk of losing control of that virus

and letting the reproduction rate go back over one

because that would mean not only a new wave of death and disease but also an economic disaster

and we would be forced once again to slam on the brakes across the whole country

and the whole economy

and reimpose restrictions in such a way as to do more and lasting damage

and so I know it is tough

and I want to get this economy moving as fast as I can

but I refuse to throw away all the effort and the sacrifice of the British people

and to risk a second major outbreak and huge loss of life and the overwhelming of the NHS

and I ask you to contain your impatience because I believe we are coming now to the end of the first phase of this conflict

and in spite of all the suffering we have so nearly succeeded

we defied so many predictions

 we did not run out of ventilators or ICU beds

 we did not allow our NHS to collapse

and on the contrary we have so far collectively shielded our NHS so that our incredible doctors and  nurses and healthcare staff have been able to shield all of us

from an outbreak that would have been far worse

and we collectively flattened the peak

  and so when we are sure that this first phase is over

and that we are meeting our five tests

  deaths falling

 NHS protected

  rate of infection down

  really sorting out the challenges of testing and PPE

avoiding a second peak

then that will be the time to move on to the second phase

in which we continue to suppress the disease

and keep the reproduction rate, the r rate, down,

but begin gradually to refine the economic and social restrictions

 and one by one to fire up the engines of this vast UK economy

 and in that process difficult judgments will be made

and we simply cannot spell out now how fast or slow or even when those changes will be made

though clearly the government will be saying much more about this in the coming days

 and I want to serve notice now that these decisions will be taken with the maximum possible transparency

 and I want to share all our working and our thinking, my thinking, with you the British people

 and of course, we will be relying as ever on the science to inform us

as we have from the beginning

but we will also be reaching out to build the biggest possible consensus

across business, across industry, across all parts of our United Kingdom

across party lines

bringing in opposition parties as far as we possibly can

because I think that is no less than what the British people would expect

and I can tell you now that preparations are under way

and have been for weeks

to allow us to win phase two of this fight as I believe we are now on track to prevail in phase one

and so I say to you finally if you can keep going in the way that you have kept going so far

 if you can help protect our NHS

to save lives

and if we as a country can show the same spirit of optimism and energy shown by Captain Tom Moore

who turns 100 this week

 if we can show the same spirit of unity and determination as we have all shown in the past six weeks

 then I have absolutely no doubt that

we will beat it together

we will come through this all the faster

 and the United Kingdom

will emerge stronger than ever before

My comment:

"Boris is Back!" is my reference to September 3, 1939 when Chamberlain appointed Churchill First Lord of the Admiralty and the fleet signaled "Winston is Back!" 

However,  I think he is partly responsible for the high death rate since he did not impose the lockdown earlier and my understanding how that happened can be found here. He will definitely suffer  political consequences, but he has learned his lesson.

1_DAY_SOONER COVID-19 Human Challenge Trials

1DAYsooner       

                How could challenge trials help speed up vaccine development?

Excerpts from

Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure

The proposed trial method would potentially cut the wait time for the rollout of an efficacious vaccine. Challenge studies (which always directly expose all participants to a pathogen to assess efficacy) generally require fewer participants, followed over a shorter period than do standard efficacy studies (in which many participants are never exposed). Rollout of an efficacious vaccine to age groups not included in the challenge studies may depend on immunological bridging, but this would be a component of the expanded safety studies discussed above. It is possible that this process could take several months shorter than reliance on standard phase 3 testing to assess efficacy. While rollout to other populations might require initial bridging studies, these could be conducted relatively quickly.

It seems clear that, in the absence of an efficacious vaccine, the global death toll from COVID-19 will be enormous. A recent modelling study suggests that, even with mitigation strategies focusing on shielding the elderly and slowing but not interrupting transmission, there may be 20 million this year [10]. If the use of human challenge helped to make the vaccine available before the epidemic has completely passed, the savings in human lives could be in the thousands or conceivably millions. Intense social distancing and related control measures, held in place for many months between now and the availability of vaccine, will themselves take a toll on economies, societies, and population health. Advancing the registration and rollout of an efficacious vaccine, even by a few months, could save many thousands of lives, and commands enormous societal value.

But a remaining key question, for deeming human challenge studies ethical, pertains to risk. Are the risks to participants, even when they are justified by the social importance of the trial and backed by participants’ willful permission, also being kept to the necessary minimum? And do the risks fall below a postulated cap on the acceptable risk of medical trials, even ones of the highest social value and with participants’ consent [15]?

The proposed challenge studies seek to contain the risk to participants in 6 different ways. First, the study will recruit only healthy patients from age groups in which the risk of severe disease and death following SARS-CoV-2 infection is low. Second, there is the possibility that the vaccine candidate will protect at least some of those who are vaccinated. Third, in the absence of an effective vaccine, a high proportion of the general population is likely to be naturally infected with SARS-CoV-2 at some point [17], including those who might participate in a challenge study; by volunteering to be artificially infected they may be just hastening an event that is likely to occur in later months anyhow. Fourth, only people with an especially high baseline risk of getting exposed during or soon after the trial period should be recruited (eg, people residing in areas with high transmission rates). Fifth, participants would be monitored carefully and frequently following the challenge and afforded the best available care if needed (eg, guaranteed access to state-of-the-art facilities of the health system, notwithstanding the possibility of severe shortages of medical care during the evolving pandemic). Sixth, by the time vaccine candidates are being tested, some therapeutics may be approved, which may reduce participants’ risk of morbidity and mortality further. For these 6 reasons, mortality and morbidity from participation notwithstanding, net mortality and morbidity from participation should remain low or negative.

Coronavirus Q&A: Predicting Pandemics

29:27 into the video  Marc Lipsitch: “Over 1500 people have contacted the authors of this paper and then gone to a website and put their names in saying I would like to be in such a trial and these are thoughtful educated people by and large who want to do something altruistic. So it is unconventional but I think potentially very promising. “

Vaccine testing

Phase 1 is for safety typically in the 10s of participants   

Phase 2 for immunogenicity   10s – 100s participants

Phase 3 for efficacy and is typically in the 1000s of participants

30:34  “So the idea would be to involve thousands but not follow them for efficacy, only for safety and immunogenicity which is quicker, and then do the challenge to evaluate efficacy and then obviously  you would need follow up to show the efficacy was true  also in other groups.”

38:20  Howard Bauchner: “Last question,  I just made you the pandemic tsar for the next year, and you have a blank check, well maybe not a blank check, although we already spent two trillion $, you have  a lot of money, Marc, what are the first three or four or five things you’d want to do? “

ML: “It’s a good question.  I would invent a time machine and turn back the clock, so that we could have prepared a little better”

Is remdesivir the drug that can kill the coronavirus?

The Economist

 Science and technology

Many hope it is the cure the world has been looking for, but nobody can yet be sure it works

Apr 17, 2020 

AN EFFECTIVE DRUG to treat covid-19 would transform the battle against the pandemic. Without one, whole countries have had to lock themselves down to limit the spread of the novel coronavirus which has infected more than 2m people and killed nearly 150,000, according to official records; the real toll is probably much greater.

An effective treatment would allow countries to loosen some of the restrictions that are strangling their economies. They would be able to risk more people catching the virus in the knowledge that they could be cured.

This hope has energised the hunt for a drug against covid-19 since the early days of the pandemic. President Donald Trump, for one, has touted hydroxychloroquine, an anti-malarial drug. But it is remdesivir, an experimental antiviral drug, that is proving the most exciting. The share price of its maker, Gilead Sciences, shot up by 12% on April 17th after a leak in STAT, an online medical publication, of a discussion suggesting impressive results of a trial with the drug.

Unlike drugs like hydroxychloroquine, which were made to treat other conditions but might have antiviral effects, remdesivir was designed from the outset to kill viruses. It is a molecule known as a “nucleotide analogue”. Its structure mimics the letters that are used to make up the RNA sequences of the virus. The idea is that when viruses try to use these pseudo-letters it gums up their works. Gilead, a drugmaker from California, developed remdesivir to treat Ebola. Although it performed poorly in this, laboratory tests have shown it to be effective against a range of viruses. Thus there is a reasonable hope that it will work against the new coronavirus, called SARS-CoV-2.

Yet science remains equivocal about whether this drug actually works for covid-19 sufferers. Two trials in China have already failed, because of lack of enrolment. (China started its trials relatively late in its epidemic, so it was hard to recruit sufficient numbers of patients.) The recent publication in the New England Journal of Medicine, of a study of remdesivir given to 53 severely afflicted patients, reported that 68% of them improved. However the study has proven divisive among scientists. To begin with, errors can be large given the small number of patients. Moreover, the trial was not “randomised”, so there is no way of knowing whether the sample properly reflects the population of severely afflicted patients. Last, there was no comparison group that was given a placebo, ie, a substance with no therapeutic effect, to establish the real effectiveness of the drug.

For all the excitement it generated, the STAT report was little more than a leaked conversation between doctors. It revolved around a trial at the University of Chicago with 125 patients, mostly severely ill with covid-19. One of the doctors is reported as saying that most of the patients had been discharged and only two had died. But even if this is correct, the lack of a placebo group makes it hard to assess the real worth of the drug. The University of Chicago itself warned that drawing any conclusions was "premature and scientifically unsound".

Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, warns that medicine is littered with instances where treatments were incorrectly believed to have strong benefits based on non-randomised data. Luckily, there are some gold-standard trials under way. One global effort, under the auspices of the World Health Organisation, began in mid-March but results are not expected until after June. Another by the National Institute of Allergy and Infectious Diseases in America could come in late May.

Even if the drug proves successful, it is still experimental, and only limited quantities of such drugs are usually available. Gilead has increased production to meet demand for use in trials. On April 5th, it said it had enough to supply more than 140,000 patients. These sorts of numbers are larger than would be required by clinical trials, so suggest that Gilead is ramping up production for clinical use. The firm also said it was hoping to increase output again as raw materials became available. Looking further ahead, at even broader use, the firm has set an “ambitious goal” of producing more than 500,000 treatment courses by October, and 1m by the end of the year, from a geographically diverse group of suppliers.

The best solution to the pandemic is still a vaccine against SARS-CoV-2; it would prevent people from catching it rather than curing them after they fall ill. But an effective medicine, even in small quantities, would make a huge difference—not least because it would speed up the development of a vaccine. The quickest way to test whether a vaccine works is to give it to a group of volunteers (and a placebo to another), and then expose them to the coronavirus. This is ethically dubious for a disease that has no known cure. A good treatment, though, would make such “human challenge” trials much more likely to go ahead.

Did Netanyahu’s technical/math background save Israel in the coronavirus crisis?

According to I24news, the US warned Israel about COVID-19 in mid-November, 2019:

“The information was also handed over to the White House, 'which did not deem it of interest'

The US government reportedly gave Israel advanced warning over the emerging threat the coronavirus posed in China around mid-November. 

According to Israeli broadcaster Channel 12, US intelligence agencies became aware of the danger posed by COVID-19 as it battered the central city of Wuhan in China's Hubei province. 

The information was then handed over to the White House, “which did not deem it of interest,” according to Channel 12

Despite the Trump administration's dismissal of the information, US intelligence decided to warn its close allies of the contagious disease, specifically NATO and Israel.”

So Trump, Boris Johnson and Netanyahu had the same information in mid-November, 2019 and yet Bibi reacted much better than both Trump and Boris Johnson and imposed stricter restrictions early on. Why such a different reaction?   

  

I think that the main difference is that Bibi has a more technical background (he’s got a Master of Science degree from MIT) whereas Boris Johnson studied humanities at Oxford and Trump has a bachelor’s degree in economics from the Wharton school.

So how does this matter?   It matters in that I think Bibi was probably more responsive to the scientists’ advice to impose strict sanctions early on since he felt and fully understood the way exponential functions like y = e**x  work, and the significance on imposing restrictions early on while there are only a few cases and that waiting would have huge consequences.

 Both Boris Johnson and Trump did not seem to understand that. From The Guardian:  “Prominent US public health adviser Dr Anthony Fauci appeared on Sunday to confirm a bombshell New York Times report which said he and other Trump administration officials recommended the implementation of physical distancing to combat the coronavirus in February, but were rebuffed for almost a month.”

In Boris Johnson’s case it seems that there had been a disconnect between the scientists who were advising him and the cabinet, and that the scientists failed to convey the danger of the initial goal of reaching herd immunity.   

It was only after the publication of the Imperial College London Report published on March 16 that both Trump and Boris Johnson changed policies, but by then they had already lost precious time.

I believe that understanding math played a role in this case. Here is a reminder: 

And just now on the 9 o’clock news,  Bibi consulted epidemiologist Marc Lipsitch  whose podcast from Feb 28, which I heard on March 5 (and transcribed), gave me the right understanding of the magnitude of the problem.  We in Israel are being well informed!  

So Israel is in the best position of the three countries and has 10 times less death per 1 M than the UK and 5 times less deaths per 1 M than the US, is testing twice as much as the US and three times as much as the UK.   

Data as of April 19, 2020 from https://www.worldometers.info/coronavirus/  

  

Coronavirus clue? Most cases aboard U.S. aircraft carrier are symptom-free

Reuters

The aircraft carrier Theodore Roosevelt (CVN-71)

Phil Stewart, Idrees Ali

WASHINGTON (Reuters) - Sweeping testing of the entire crew of the coronavirus-stricken U.S. aircraft carrier Theodore Roosevelt may have revealed a clue about the pandemic: The majority of the positive cases so far are among sailors who are asymptomatic, officials say.

The possibility that the coronavirus spreads in a mostly stealthy mode among a population of largely young, healthy people showing no symptoms could have major implications for U.S. policy-makers, who are considering how and when to reopen the economy.

It also renews questions about the extent to which U.S. testing of just the people suspected of being infected is actually capturing the spread of the virus in the United States and around the world.

The Navy’s testing of the entire 4,800-member crew of the aircraft carrier - which is about 94% complete - was an extraordinary move in a headline-grabbing case that has already led to the firing of the carrier’s captain and the resignation of the Navy’s top civilian official.

Roughly 60 percent of the over 600 sailors who tested positive so far have not shown symptoms of COVID-19, the potentially lethal respiratory disease caused by the coronavirus, the Navy says. The service did not speculate about how many might later develop symptoms or remain asymptomatic.

“With regard to COVID-19, we’re learning that stealth in the form of asymptomatic transmission is this adversary’s secret power,” said Rear Admiral Bruce Gillingham, surgeon general of the Navy.

The figure is higher than the 25% to 50% range offered on April 5 by Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a member of President Donald Trump’s coronavirus task force.

DISCONCERTING’ DATA FOR PENTAGON

Defense Secretary Mark Esper, speaking in a television interview on Thursday, said the number of asymptomatic cases from the carrier was “disconcerting.”

“It has revealed a new dynamic of this virus: that it can be carried by normal, healthy people who have no idea whatsoever that they are carrying it,” Esper told NBC’s “Today” morning show.

Such data present challenges to the Pentagon, which is deployed around the world, sometimes in confined environments like submarines, ships and aircraft.

Testing the entire military is not yet feasible, given still-limited testing capacity, officials say, and detecting enough cases without tests is impossible if most cases are asymptomatic.

The U.S. coronavirus death toll - the highest in the world - surged past 31,000 on Thursday after doubling in a week.

It also claimed the life of a sailor from the Theodore Roosevelt this week. Five other members of the crew are hospitalized.

NUMBERS UNKNOWN

Still, the case of the Theodore Roosevelt offers a case study for researchers about how the virus spreads asymptomatically in a confined environment among mostly younger adults.

That cohort has been somewhat underrepresented in the epidemiological data so far, said William Schaffner, an infectious disease specialist at Vanderbilt University Medical Center.

“The findings are of enormous interest because the proportion of people who are asymptomatic is just simply not known,” Schaffner said, when asked about the Navy’s data.

Vice Admiral Phillip Sawyer, a deputy chief of naval operations at the center of the Navy’s coronavirus response efforts, presented the 60% figure in a call with a small group of reporters on Wednesday.

But he declined to speculate about the implications.

“I don’t know if we’re proving something different,” Sawyer said.

“I do agree that we are providing some data that some other organizations might not have.”

Mobileye mogul’s model for lifting the coronavirus lockdown

The Jerusalem Post

   By MAAYAN JAFFE-HOFFMAN  

APRIL 13, 2020 23:09   

The man who developed the driverless technology firm Mobileye and then sold it to Intel for $15.3 billion – the largest Israeli exit to date and the world's biggest purchase of a company solely focused on the autonomous driving sector – says he has a plan to get Israelis out of lockdown and back to work.

“Physicians help us when we are sick, but they are not going to release us from this crisis,” Amnon Shashua told The Jerusalem Post. “This is a problem to be solved by mathematicians, statisticians, computer scientists, epidemiologists and economists… Our duty is to make sure that all the right minds are putting their CPU power into this problem.”

Shashua and Prof. Shai Shalev-Shwartz of Hebrew University’s Computer Science Department came up with a plan, which they first laid out on March 26 on the online publishing platform Medium in English in an essay titled, “Can we Contain COVID-19 without Locking down the Economy?” The next week, Shashua presented his proposal before the Knesset Coronavirus Committee. On Sunday, he updated and adapted the plan in Hebrew.

Now, it is among the programs being considered by the National Security Council and eventually the prime minister.

The model: Risk-based selective quarantine.

The idea, Shashua explained, is that the population can be divided into low- and high-risk groups. People under the age of 67 and without underlying medical conditions are low risk. Those over 67 – “which represents the retired segment of society” – or with co-morbidities are high-risk.

“The low-risk group... is released to their daily routine while following certain distancing protocols that are aimed at slowing the spread – while keeping the economy undisrupted to a large degree, but ultimately reaching a herd immunity level,” and “quarantine the high-risk,” they wrote.

Given the herd immunity of the low-risk group, the team predicted, the country could gradually release the high-risk population.

Shashua admitted that we still don’t even know for sure that a person develops immunity to COVID-19 and cannot be reinfected with the virus a second time – although with most similar viruses, this is the case. Nonetheless, in his latest version, he maintains that this is not an essential factor.

“The question is how do we guarantee that the health system will not be overwhelmed during the spread of the virus in the low-risk group?” Shashua said, explaining that the program is designed to allow the health system to cope with the expected number of severe cases.

The percentage of Israelis on ventilators that are from the low-risk group is around 15%, Shashua explained. Through a complex series of mathematical equations that are included in the essay, Shashua and Shalev-Shwartz determined that the number of ventilators that would be needed to handle the low-risk group if the country rolled out risk-based selective quarantine would be around 2,000.

According to the Health Ministry, Israel has around 3,500 ventilators, or roughly one for every 2,500 citizens. And Shashua said that the need for 2,000 ventilators was pessimistic.

“What we propose here is a worst-case analysis,” they wrote on Medium. “The idea is to adopt a pessimistic view and show that even under this pessimistic view, the health system is not likely to collapse” with this plan.

“Everyone is putting their hopes into surgical quarantine,” Shashua said, the idea that the country will test anyone who has coronavirus symptoms. If the person tests positive, he or she is quarantined, epidemiological tracking is carried out and all those who they were in contact with are also isolated.

“Testing is expensive and finite,” he argued. “And even if you did try to test the entire symptomatic population, chances are you will miss people and then you will have an exponential increase of infection.”

Moreover, since as many as half of all coronavirus patients are asymptomatic, they spread the disease but don’t get tested. Add to these people those who will not cooperate and report their symptoms because they don’t want to be tested, and the virus spreads quickly.

“So, take all your technology and apply it to the high-risk group – surgically quarantine the high-risk group,” he said, arguing that screenings should be done daily in senior homes, for example.

“A full population-wide quarantine is not a solution in itself,” they wrote in their essay. “The lockdown could take anywhere from weeks to months. This is the safest route but does not prevent a ‘second wave’ from occurring.”

He said that in all other selective quarantine models, the high-and low-risk are equally susceptible to be infected so that even if the health system is not overwhelmed, the mortality of the high-risk group is still likely to be higher than in the risk-based model.

“We are in one of the biggest crises of humanity in 100 years… and I don’t hear a diverse set of voices in this crisis. I only hear the voice of the Health Ministry, and they are in hysterics,” Shashua stressed.

“Send the young kids to school,” he continued. “Their parents are the lowest-risk population. Release the lock-down on these people. You have flexibility with the low-risk population, and you can maintain the economy this way for 18 months until a cure or vaccine is available.

“This strategy is backed by mathematics,” he concluded.

*** 

My comment:  

I am worried that this might end up similar to what happened in the UK when they initially wanted to build herd immunity, in that all seems very logical until young people from the low-risk group start dying . This is the part of the paper I am worried about:

“We ignored the fact that some severe cases could end up in the mortality statistics even when given proper care. In fact, there are two probabilities to estimate (i) the probability of being in the ”severe” category among the low-risk group, and (ii) the probability of mortality given proper care.  We have bounded the former and ignored the latter.   The reason for doing so is that the latter is beyond the scope of this paper because it is essentially a moral tradeoff between ”safety” and ”usefulness” that is employed in every aspect of society.   For example, society does not put a lockdown on passenger car use in order to significantly reduce car accidents even though such a lockdown will save lives. Likewise, governments do not allocate infinite budgets for the health system even though there is a correlation between increased investments and saving lives.”

There are no easy solutions and this could be the least painful one, but the moral tradeoffs will have to be discussed.  Just like epidemiologist Marc Lipsitch’s proposal  that 100 altruistic young people should volunteer to get a vaccine for Covid-19 and then be infected with the coronavirus on purpose.