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Emerging from Virus:
Academics Step Up
By Shlomo Maital
Public health officials, who are in control in most countries, have their hands full, dealing with the medical crisis. So it is up to us, academics and others, to begin weighing options for emerging from the lockdown.
An interuniversity team led by Tel Aviv U. President Ariel Porat and Weizmann Institute President Alon Chen, have prepared an excellent 27-page plan. Details are reported by Haaretz journalist Meirav Arlosoroff.
(Suggestion to other countries: why not set up a similar team? Include epidemiologists, virologists, economics, psychology, law, computer science, even quantitative physics, and of course public health).
Here are the options the experts present. Option One: Maintain the strick lockdown. Option Two: the opposite, speed up the rate of infection among Israel’s non-vulnerable population (is there such a thing?) to achieve ‘herd immunity’ (VERY bad term – we are NOT a herd… why not population immunity? Or mass immunity?). Under the second option, the elderly would remain in isolation for their protection.
Neither are very attractive, are they? There is a missing link – widespread testing, to provide detailed data. The required number of tests is not available.
So the committee suggests a third option — a “gradual lifting of the lockdown while officials carefully monitor numbers related to the pandemic. Divide Israel into equally sized ‘risk zones’ based on how far and wide the coronavirus has spread. Red zones would maintain total lockdown. Yellow zones would be where people are allowed to leave their homes for work, provide they stay inside the yellow zone! In Green Zones residents are free to go to their jobs, including jobs outside their zone. Those showing symptoms remain in quarantine in all three zones. Those shown to be immune are free to go wherever they please. (A key here is a serological antibody test, not yet widely available) Places of work would reopen, subject to strict rules on hygiene and social distancing. Workplaces would be graded, according to how risky they are for a ‘second wave’ outbreak. Workplaces barred from opening would be exempt from rent.
The committee also recommended tax incentives to encourage work from home.
Division into red, orange, green zones is based on sophisticated mathematical models that predict the epidemic’s spread – along with high levels of testing. Sampling tests that show less the 2-3% infection rates would enable ease of the lockdown. Green zones are where the number of serious cases doesn’t exceed 100 and the infection rate is less than 8 %. Technologies like location technology and artificial intelligence will be used to predict the possible rate of contagion.
Since test kits are in short supply, a model for sampling should be used, for each cone, including children, so schools can reopen.
The Committee says that a measured exit from the lockdown can and should already begin. It calls for allowing between 900,000 and 1.5 million workers to return to their jobs. This is between one quarter and a third of Israel’s work force.
“Data from the math models shows that the virus’ high infection rate does not allow for complete release from lockdown, even for Green zones”, they note. Social distancing still is the main tool, to reduce infection parameters by a factor of 2 to 3. Areas of especially high infection must receive special treatment, such as the ultra-Orthodox areas.
I believe that each country needs its own inter-University committee of this sort, because each country has its own culture and unique circumstances. It needs to be a non-governmental civilian effort, because governments are simply focused on the day-to-day.
Emerging from Plague: Thinking Ahead
By Shlomo Maital
With many nations still weeks from the ‘apex’ (the peak number of COVID-19 cases), it seems premature to discuss what the press and experts call ‘exit’ strategies – the period AFTER the plague. The word itself is wrongheaded. Exit strategies are what startups do, when they succeed in creating value and need to capture the wealth and return it to their investors and founders. Usually, by acquisition or issuing shares and selling them.
We do not seek an ‘exit’ strategy. We need an ‘emergence’ strategy, when we come out of our tunnels and rabbit holes and resume our regular lives. Words matter. There is no ‘exit’ from COVID-19, because it will remain endemic for a long time. There is ‘emergence’…with great caution.
How best can this be done? How should our governments be planning emergence?
Here are some wise thoughts by Prof. Ron Balicer, a person with whom I’ve worked, Chief Innovation Officer at Israel’s Clalit Health Services (a large HMO) and a member of the Health Ministry’s Epidemic Management Team. His article was published in the daily Haaretz newspaper.
“Mathematical models and past experience show that the spread of infection in communities living in overcrowded conditions can spark a renewed and serious outbreak among all segments of society. From an epidemiological perspective, Israel’s population (as well as, to a large extent, that of the Palestinian Authority) constitutes interconnecting “communicating vessels” with immediate collateral impact.
“In the current setting, the most stable and reliable marker of population-based trends in disease dissemination is the trend in the numbers of severely ill and respirator-aided Covid-19 patients. However, this marker lags behind the real-time spread by several weeks. If we continue to see that this marker is stabilizing – a collective sigh of relief will be heard. In the meantime, we must not wait for absolute certainty before planning the next phase of contending with this crisis and its attendant closure: the exit strategy.
“I propose two preconditions for initiating this strategy: The first is a significant halt in the exponential rate of the disease spread, and the availability of a substantial number of free beds in intensive care units, which will serve as the buffer and allow a margin of error to prevent a collapse should easing of the lockdown spur a sudden increase in infections. Let’s use some numbers as an illustration: In the optimistic scenario in which there are up to 100 seriously ill or respirated people in Israel on the eve of Passover, the distance between where we are now and the point of health system insufficiency is 4-5 doublings of the number of people needing artificial respiration. In recent weeks we’ve seen that the doubling time is three days, with faster rates in some localities.
“The second condition required before embarking on that strategy is to obtain a real-time intelligence assessment, detailed and updated, regarding the rates of infection among different communities. This is a precondition for resorting to a rapid intervention vis-a-vis every new patient, as is happening in countries that have managed to successfully curb the epidemic to date.
“In other words, there needs to be an efficient system of conducting lab tests for Covid-19 among a wide swathe of the population, in order to exercise an effective exit strategy. To that end, Israel is hopefully gaining what will be an exceptional per-capita testing capacity, even in comparison to the advanced countries. The 30,000 daily tests we hope to be able to conduct in a few weeks’ time should be conducted dynamically and judiciously in order to facilitate this intelligence assessment.
“An exit strategy requires a change: a transition from social distancing and full lockdown enforced on the entire population in a sweeping and non-selective manner, to a new status quo. This new routine could be based on three components: a fast and focused effort to locate and tackle infected individuals; a differential and dynamic lockdown policy among targeted communities; and designated policies for allowing recovered immune patients to return to normal life and take a continuously increasing role in sustaining the economy.
“All this needs to be done while adapting the economy to working remotely with strong delivery services, to daily conduct based on social distancing and environmental hygiene in every workplace, and to continued construction of medical infrastructure, with maximal protection of medical teams.
“As part of the new status quo, the older population will remain as isolated “islands” within each community for a longer period, having its physical, emotional and social needs met on a daily basis.
[“There are several components –] The first component involves the efficient and determined tracking down of newly infected people and their rapid removal from the infective pool. This demands a rapid “closing of the circle” capacity. The multi-stage process of locating people suspected of being infected and having them tested for Covid-19, the rapid quarantine of sick people removed from home, an epidemiological investigation and a quick isolation of their contacts – all this must be accomplished with speed and precision. Moreover, it must be done in large numbers of cases and contacts.
For this condition to be met, a combination of capabilities – which at present are suboptimal – must be achieved. These include extensive and carefully thought-out testing of all people who have been in contact with the new cases; the ability to obtain results quickly for those who tested positive, and their removal from their families to hotels or other facilities; both manual and electronic epidemiological investigation, contact tracing and their quarantine; and firm enforcement of social-distancing instructions, among all segments of society.
“The second component is a geographically differential lockdown/quarantine policy, dynamically updated according to the available data. Communities in which there is persistent transmission of the virus, and those with individuals who are particlarly vulnerable, must remain under a stricter lockdown, whereas communities in which transmission has effectively been mitigated can enjoy a continued easing of restrictions.
“The country can be divided into sub-regions. Imagine that one day the radio announces that areas A, B and D can go to work from now on, whereas area C (i.e., Jerusalem or Rahat) is still to be confined to home. On another day, area A might be asked to reinstate a four-week lockdown, in view of ensuing infection. Obviously, such a policy won’t completely prevent “leakage” between areas and communities, but it will significantly head it off, and with the other components in place, this may be sufficient.
“In order to facilitate and supervise such a policy, an ongoing process of real-time intelligence-gathering must be established, including the continual monitoring of self-reported symptoms and continuous screening for infected people, in order to detect potential outbreaks as early as possible.
“The third component: Once serologic blood tests will become largely available, we will be able to conduct mass testing and define a growing number of recovered immune individuals. This group will assume an increasing role in re-operating businesses with few restrictions. Moreover, older people who got sick and recovered could also return to a “new normal” routine.
“In my view, easing of the closure will take place as a continuous, gradual process of experimentation and re-assessment, in cycles of several weeks each. In each cycle, significant restrictions will be lifted, followed by a tense watchful waiting period of several weeks, required to evaluate its impact on the dissemination rates. If the doubling time does not accelerate significantly, and the safety margin of available intensive care beds has not been reduced to the danger level, further easing of measures can be then implemented.”
A Vaccine Is On The Way – Soon?
By Shlomo Maital
Today’s Jerusalem Post daily paper, published in Jerusalem, brings some much-needed good news about progress in creating a vaccine against COVID-19.
The report notes:
“A team of Israeli researchers says that they are days away from completing the production of the active component of a coronavirus vaccine that could be tested on humans as early as June 1. “We are in the final stages and within a few days we will hold the proteins – the active component of the vaccine,” Dr. Chen Katz, group leader of MIGAL’s biotechnology group, told The Jerusalem Post. In late February, MIGAL [The Galilee Research Institute] committed to completing production of its vaccine within three weeks and having it on the market in 90 days. Katz said they were slightly delayed because it took longer than expected to receive the genetic construct that they ordered from China due to the airways being closed and it having to be rerouted.”
(Note: the ‘genetic construct’ from China, is simply the RNA ribonucleic acid that defines COVID-19 — shame that cancellation of flights from China to Israel caused the delay – every day counts!).
“As a reminder, for the past four years, researchers at MIGAL scientists have been developing a vaccine against infectious bronchitis virus (IBV), which causes a bronchial disease affecting poultry. The effectiveness of the vaccine has been proven in preclinical trials carried out at the Veterinary Institute.”
Amazing that chickens, maybe, and their vaccine can help save human lives?
The report continues: “Our basic concept was to develop the technology and not specifically a vaccine for this kind or that kind of virus,” said Katz. “The scientific framework for the vaccine is based on a new protein expression vector, which forms and secretes a chimeric soluble protein that delivers the viral antigen into mucosal tissues by self-activated endocytosis, causing the body to form antibodies against the virus.”
What does this mean? Basically: The vaccine helps the body produce a key protein able to penetrate the cells infected by COVID-19 in the throat and lung mucous. How does it penetrate? Endocytosis is “the process of actively transporting molecules into the cell by engulfing it with its membrane.” This helps the cell produce antibodies that kill the virus, before it can kill the cell and reproduce, creating millions of new viruses that spread through the lungs.
“In preclinical trials, the team demonstrated that the oral vaccination induces high levels of specific anti-IBV antibodies, “ a MAGAL expert said.
A worldwide race is on, to develop an effective safe COVID-19 vaccine. Whoever wins, humanity will be the big winner. This is one race that can benefit everyone, even the spectators.
New Thinking on Alzheimer’s: Time for a Paradigm Shift?
By Shlomo Maital
Scientific breakthroughs come from iconoclastic researchers who are not afraid to smash consensus paradigms. Take, for instance, Prof. Michal Schwarz, of Israel’s Weizmann Institute. Here is what she told this week’s Haaretz (Hebrew) reporter:
The puzzle I pieced together is correct, and now I see the whole picture – how my research approach, for years against the consensus, has become one of the central focal points for research on all degenerative (neural) diseases.
The paradigm shift Schwarz has helped bring about is simple. Many researchers follow the “I dropped a coin” model – they look for it under the corner streetlight, instead of in dark corners, where it fell, because…. “that’s where the light is”. Alzheimer’s? Gooey proteins gumming up the brain and causing death? Look for cures that eliminate or prevent the protein directly, in the brain. Under the light.
But Schwarz? Let’s help the body’s own anti-immune system, outside the brain, fight those plaque accumulations that damage the brain. Last year the Daily Telegraph quoted Dr. Doug Brown, a leading Alzheimer’s researcher: “Repurposing drugs that already work for other conditions could provide us with a shortcut to new dementia treatments, and is a key aspect of our Drug Discovery programme.”
Here ‘s how the Daily Telegraph described Schwarz’s paradigm shift, in 2016: “The drugs, known as PD-1 blockers, effectively prevent the immune system from switching off, allowing a continuous cascade of soldier cells to fight disease and clear out damage in the body. In the case of Alzheimer’s disease sticky amyloid plaques build up which stop brain cells communicating with each other. But when mice, engineered to have Alzheimer’s symptoms, were given injections of the drug the amount of amyloid in their brains halved, and the animals were able to complete a maze task in the same time as control mice. Last year the first PD-1 blocker drug Keytruda was approved for use on the NHS by the National Institute for Health and Care Excellence so it is already known to be a safe treatment.
“Lead author Prof Michal Schwartz of the Weizmann Institute of Science, Rehovot, Israel, said that in Alzheimer’s a weakened immune system could be preventing the body from repairing itself. “We are extremely excited about our new study, we believe it is a game changer both conceptually and therapeutically,” she said.
Her research was published in the leading journal Nature Medicine.
Prof. Schwarz added: (in Hebrew): “In contrast to veteran old-time researchers, students have no history of believing dogma (existing paradigms)…they are fresh ears and eyes, without preconceptions. They were especially excited, with me, at our results, and joined my research and contributed to moving it forward, and some of them are continuing in my wake.”
As a (very) senior citizen, I have deep interest in breakthrough research on Alzheimer’s – half of those over 85 have it, at least early versions. Congratulations to Prof. Schwarz for becoming a woman scientist and for leading a paradigm shift that may help millions – including those in countries that despise Israel.
National Happiness – 2013 Rankings
By Shlomo Maital
Three eminent economists – Richard Layard, John Helliwell and Jeffrey Sachs – combine to prepare an annual World Happiness Report. Their measure is based on self-assessed happiness, interpreted as “satisfaction with life” together with the perceived emotion of wellbeing. In their latest report, for the years 2010-12, (see above), Scandinavian and Northern European countries rank highest, along with Canada, Austria, and surprisingly, my country Israel (11th), despite the Mideast conflict, and Costa Rica, a relatively poor but serene and beautiful country. Note that Mexico, at 16th, ranks above the United States, despite the latter’s $50,000 GDP per capita.
Why? The answer is simple. Happiness, note the authors, is driven in part by the standard of living (per capita GDP), but also by life expectancy, social support, freedom to make life choices, and generosity. This is why Qatar, the wealthiest country in the world by far, with per capita GDP of nearly $100,000, ranks only 27th, because it is a rigid autocracy.
I am amazed at how poorly individuals and whole nations practice the simple art of best-practice benchmarking. If you are a political leader, and if your avowed goal is to improve the wellbeing of your citizens, the ones who elected you, would you not explore the world and visit the places in which people are the happiest, and try to find out why? And would you not try to bring home some of the “recipes” they use – income equality, social support, generosity, social cohesion?
I get this response very often when I make this argument: Israel is not Denmark. Followed by all the excuses. And my response is: Well – why isn’t it? Can we make it so?
There is a lesson for individuals in this Report, not just for countries. True, you do need a basic level of income to be happy. But you also need the love and support of family, the generosity of others, and good health (supplied, as a public good “health care”, by good governments, or at least they should). Even if you have high income, if you lack the other ingredients, the income may not help much. Keep this in mind.
TIMnovate 