A 30-second Corona test: India-Israel collaboration

October 11, 2020 in Uncategorized | Leave a comment

by Shlomo Maital

Today’s Jerusalem Post reports on a fascinating Israel-India collaboration, to develop something the world has needed for a very long time, since the start of the pandemic: a quick (instant) test!

One of the key implications of a 30-second test is that air travellers will be able to confirm they are virus-free instantly — and board without hassle. This could save civil aviation, which is in a desperate crisis — in the US alone, some 130,000 civil aviation employees face permanent layoffs.

Here is the report by Maayan Jaffee-Hoffman:

“A 30-second coronavirus detection test being developed by India and Israel should be ready in “a matter of days,” Israeli Ambassador to India Ron Malka told the Indian news agency PTI on Friday. “All the thresholds have been passed.”

The operation has been dubbed “Open Skies,” and Malka said he believes the testing kit will enable the world to begin opening the skies, since the technology simply requires a person to blow into a tube and the results become available in less than a minute. It is also very cheap to carry out, as the results are delivered locally without the logistics and cost of sending the sample to a lab. ”

If You Measure The Wrong Thing: You DO the Wrong Thing – Let’s Cluster-Bust!

October 3, 2020 in Uncategorized | Leave a comment

by Shlomo Maital

    Policy begins with measurement.  If you measure wrongly, you act wrongly.  Result: Fiasco.

    My country Israel is deep in a COVID-19 second wave, far worse than the first, with 7,000 and more new cases daily, for a small country of some 9 million people.  There are nearly 900 people in intensive care – stretching ICU capacity to the limit.  Medical staff, working non-stop since February, are crushed under the burden. And now, a country-wide severe lockdown, closing businesses and schools, closing everything.

    So why is this a fiasco?  It is explained clearly in this article:  “This Overlooked Variable Is the Key to the Pandemic. It’s not R0.”  ZEYNEP TUFEKCI.   SEPTEMBER 30, 2020    The Atlantic. 

    This is a very long blog.  So here is a brief summary.  Political leaders, guided by public health experts, are focused on R0 – this is the AVERAGE number of people infected by one person already infected.  R0 bigger than one:  exponential spread.  R0 less than one:  negative exponential decline.  So the goal is: Get R0 down.

    Here is the problem. R0 is an average.  Misleading.  Why?  Consider a group of two. One is a millionaire.  One is a pauper.  There average income is $500,000.  So – all is well?

    Most people infected with COVID-19 do not spread it.  A few spread it as super-spreaders.  Why not focus on the super-spreaders?  Why shut down everything, just to catch that handful of super-spreaders?   “K” is a statistical measure of “dispersion” or “scatter” – do many people infect many others, or do a very few infect many others?  Because, if it is the latter – then if we can find the super-spreaders, we can halt the spread, without disastrously shutting down the whole world!

   And – how do you find the super-spreaders?   Backward tracing.  Conventionally, we trace forward.  You have COVID-19?  OK – with whom did you associate? And with whom did each of those associate?

    Backward tracing means:  Take a thousand persons infected in a given place.  Work backward, to see who was it and where was it and when was it that they were infected?  With the goal of finding that COVID-19 Mary – that super-spreader!   

     For example:  At the Rose Garden ceremony introducing Judge Amy Barrett – who in the front row infected so many people, including the President, Hope Hicks, the campaign manager, and so many others?   And most important – shut down mass events – like bars, weddings, and Trump rallies – that super-spread virus.

    And now, the whole story.

= = = = =

     The R mentioned in the daily press briefings represents an average of the whole country or region, involving millions of people. But its single value hides many differences between individuals and their impact on virus transmission.

      Rather than assuming that every infected person and every contact they make follows the same pattern (as with the R number), scientists working on epidemic models allow for the number of new cases caused by each infected person to vary randomly.  Some people might have high viral loads or might simply cough more and hence spread the virus more effectively.   Many people, although ill and highly infectious, don’t show any symptoms. They might make many contacts without realising they pose a danger to others. An example from history is the infamous Mary Mallon (“Typhoid Mary”), a cook in New York City in the early 1900s. Although she carried typhoid bacteria, she didn’t show any symptoms and is believed to have infected more than 50 people over seven years.

   Here is what Zeynep Tufekci writes:

  “…. averages aren’t always useful for understanding the distribution of a phenomenon, especially if it has widely varying behavior. If Amazon’s CEO, Jeff Bezos, walks into a bar with 100 regular people in it, the average wealth in that bar suddenly exceeds $1 billion. If I also walk into that bar, not much will change. Clearly, the average is not that useful a number to understand the distribution of wealth in that bar, or how to change it. Sometimes, the mean is not the message. Meanwhile, if the bar has a person infected with COVID-19, and if it is also poorly ventilated and loud, causing people to speak loudly at close range, almost everyone in the room could potentially be infected—a pattern that’s been observed many times since the pandemic begin, and that is similarly not captured by R. That’s where the dispersion comes in.    There are COVID-19 incidents in which a single person likely infected 80 percent or more of the people in the room in just a few hours. But, at other times, COVID-19 can be surprisingly much less contagious. Overdispersion and super-spreading of this virus are found in research across the globe. A growing number of studies estimate that a majority of infected people may not infect a single other person. A recent paper found that in Hong Kong, which had extensive testing and contact tracing, about 19 percent of cases were responsible for 80 percent of transmission, while 69 percent of cases did not infect another person. This finding is not rare: Multiple studies from the beginning have suggested that as few as 10 to 20 percent of infected people may be responsible for as much as 80 to 90 percent of transmission, and that many people barely transmit it.”

     Notice this:  It is the 80/20 rules so well known in management.  20% of the people do 80% of the work.  19% of the cases cause 80% of the transmission.  So the goal has to be not R0  but K:  FIND THOSE 19%!!!  STOP THOSE MASS EVENT WHERE THE 19% ARE SPREADING VIRUS!.

    OK.  Prove it.    So here is Japan’s approach based on “K”.

“Hitoshi Oshitani, a member of the National COVID-19 Cluster Taskforce at Japan’s Ministry of Health, Labour and Welfare and a professor at Tohoku University who told me that Japan focused on the overdispersion impact from early on, likens his country’s approach to looking at a forest and trying to find the clusters, not the trees. Meanwhile, he believes, the Western world was getting distracted by the trees, and got lost among them. To fight a super-spreading disease effectively, policy makers need to figure out why super-spreading happens, and they need to understand how it affects everything, including our contact-tracing methods and our testing regimes.

“In study after study, we see that super-spreading clusters of COVID-19 almost overwhelmingly occur in poorly ventilated, indoor environments where many people congregate over time—weddings, churches, choirs, gyms, funerals, restaurants, and such—especially when there is loud talking or singing without masks.”

   And now – my country Israel.  28% of Ultra-Orthodox tested for coronavirus proved positive.  Their lifestyle focuses on community prayer and celebration.  Some 40% of all new cases come from this community, which is only a small fraction of the population.

    Yet the whole country is locked down by the Prime Minister and cabinet. Why?  To focus on the Ultra-Orthodox would be discriminatory,  racist, anti-Semitic – and worst of all, politically damaging to the Prime Minister, who needs their votes and support, in his coalition.

     So Israel’s “K” is small.  We have superspreaders. But because of politics, we manage our policies based on R0.     When Israel’s Project Manager for COVID-19 control, Dr. Roni Gamzu, mentioned the Ultra-Orthodox as super-spreaders, based on medical evidence, he was violently attacked and forced to apologize.

      Sad.

   So let us give  Tufekci the last word – a word of hope.  “Could we get back to a much more normal life by focusing on limiting the conditions for super-spreading events, aggressively engaging in cluster-busting, and deploying cheap, rapid mass tests—that is, once we get our case numbers down to low enough numbers to carry out such a strategy? (Many places with low community transmission could start immediately.) Once we look for and see the forest, it becomes easier to find our way out.”

Why Rwanda Is Far Smarter Than the US –Dealing with COVID-19

September 29, 2020 in Global Crisis Blog, Innovation Blog | Tags: , , | Leave a comment

Why Rwanda Is Far Smarter Than the US –

Dealing with COVID-19

By Shlomo Maital

   Consider Rwanda. This small African country in south-central Africa, landlocked, has about 12 million people, with GDP per capita of about $2,600. This is only 4% of America’s per capita GDP. So Americans are 25 times wealthier than Rwandans…. But – is the US leader as smart as Rwanda’s, Paul Kagame?   4% as smart?

   Rwanda has struggled to move beyond the terrible massacre/genocide that occurred between April and July 1994, which killed between half a million and a million Tutsi – 70% of the total Tutsi population in Rwanda.

   Here is how Jason Beaubien, National Public Radio, described Rwanda’s success in controlling COVID-19. First the numbers:

Cases

4,789

 Recovered

3,080

 Deaths

29

Now Beaubien:

   “A robot introduces itself to patients in Kigali, Rwanda. The robots, used in Rwanda’s treatment centers, can screen people for COVID-19 and deliver food and medication, among other tasks. The robots were donated by the United Nations Development Program and the Rwanda Ministry of ICT and Innovation.

     “In some places in the world right now, getting tested for COVID-19 remains difficult or nearly impossible. In Rwanda, you might just get tested randomly as you’re going down the street.

     “So whenever someone is driving a vehicle, bicycle, motorcycle or even walking, everyone is asked if you wish to get tested,” says Sabin Nsanzimana, director general of the Rwanda Biomedical Center, which is the arm of the ministry of health that’s in charge of tackling COVID-19. Health officials in personal protective equipment administer the test. Nsanzimana says the testing is voluntary, although some others say refusal is frowned upon.

“The sample collection — from a swab up the nose — and filling out the contact information paperwork takes about five minutes.

“All these samples are sent that day to the lab,” Nsanzimana says. “We have a big lab here in Kigali. We have also six other labs in the other provinces.”

   “Despite being classified by the World Bank as a low-income country, and despite its limited resources, Rwanda has vowed to identify every coronavirus case. Anyone who tests positive is immediately quarantined at a dedicated COVID-19 clinic. Any contacts of that case who are deemed at high risk are also quarantined, either at a clinic or at home, until they can be tested.

     Kagame is controversial; he is accused of being dictatorial and anti-democratic. That may be.   But he and his country have done much much better than the wealthy United States, in protecting its citizens.

     Remember what President Trump called some African countries?   In 2018?   S???hole countries? Hmmm.  

SARS-COV-2 Has One Big Trick – Have We Just Discovered It?

September 26, 2020 in Global Crisis Blog, Innovation Blog | Tags: , , | Leave a comment

SARS-COV-2 Has One Big Trick – Have We Just Discovered It?

By Shlomo Maital

   According to the India Times’ Economic Times:   SARS-COV-2 virus has one big trick – and it may be that scientists have just figured out what it is.

   “It looks like this virus has one big trick,” said Shane Crotty, a professor in the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology in California. “That big trick is to avoid the initial innate immune response for a significant period of time and, in particular, avoid an early type-1 interferon response.”

   According to the India Times: The work highlights the potential for interferon-based therapies to enlarge a slowly accumulating range of Covid-19 treatments. These include Gilead Sciences’ remdesivir and convalescent plasma, a component of the blood of recovered patients that may contain beneficial immune factors.  These treatments provide limited benefit and are typically used in very sick, hospitalized patients. The possibility that interferon may help some people is enticing because it appears most efficacious in the early stages of infection when life-threatening respiratory failure could still be averted. Dozens of studies of interferon treatment are now recruiting Covid-19 patients.

   How did the scientists figure this out? Here is the story:

      When two brothers fell critically ill with Covid-19 around the same time in March, their doctors were baffled. Both were young — 29 and 31 years old — and healthy. Yet within days they couldn’t breathe on their own and, tragically, one of them died. Two weeks later, when a second pair of Covid-stricken brothers, both in their 20s, also appeared in the Netherlands, geneticists were called in to investigate. What they uncovered was a path leading from severe cases, genetic variations and gender differences to a loss of immune function that may ultimately yield a new approach to treating thousands of coronavirus patients.   The common thread in the research is the lack of a substance called interferon that helps orchestrate the body’s defence against viral pathogens and can be infused to treat conditions such as infectious hepatitis. Now, increasing evidence suggests that some Covid-19 patients get very ill because of an impaired interferon response. Landmark studies published on Thursday in the journal Science showed that insufficient interferon may lurk at a dangerous turning point in SARS-CoV-2 infections.

See also:

“Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients”   Science 07 Aug 2020: Vol. 369, Issue 6504, pp. 718-724

 

COVID-19 Vaccines: What We Know

September 24, 2020 in Global Crisis Blog, Innovation Blog | Tags: , | Leave a comment

COVID-19 Vaccines: What We Know

By Shlomo Maital

   In my country Israel, there are more new daily cases per million population than anywhere in the world. Europe too is undergoing a second wave; and many states in the United States are also seeing increasing morbidity. So – everywhere, we await a vaccine.

   Over a hundred different efforts are underway to create, produce and administer COVID-19 vaccines.   Here is what we know so far, based on a very clear, lucid website sponsored by the Children’s Hospital of Philadelphia. This vaccine effort is an amazing global effort, led by the top scientific minds, trying a wide variety of creative approaches, some tried and true, some radical and innovative. One or more of them will save humanity!

     What types of vaccine are being tested?

    Several.

   * Inactivated vaccine — The whole virus is killed with a chemical and used to make the vaccine. This is the same approach that is used to make the inactivated polio (shot), hepatitis A and rabies vaccines;

 *Subunit vaccine — A piece of the virus that is important for immunity, like the spike protein of COVID-19, is used to make the vaccine. This is the same approach that is used to make the hepatitis and human papillomavirus vaccines.

* Weakened, live viral vaccine — The virus is grown in the lab in cells different from those it infects in people. As the virus gets better at growing in the lab, it becomes less capable of reproducing in people. The weakened virus is then used to make the vaccine. When the weakened virus is given to people, it can reproduce enough to generate an immune response, but not enough to make the person sick. This is the same approach that is used to make the measles, mumps, rubella, chickenpox and one of the rotavirus vaccines.

   * Replicating viral vector vaccine — In this case, scientists take a virus that doesn’t cause disease in people (called a vector virus) and add a gene that codes for, in this case, the coronavirus spike protein. Genes are blueprints that tell cells how to make proteins. The spike protein of COVID-19 is important because it attaches the virus to cells. When the vaccine is given, the vector virus reproduces in cells and the immune system makes antibodies against its proteins, which now includes the COVID-19 spike protein. As a result, the antibodies directed against the spike protein will prevent COVID-19 from binding to cells, and, therefore, prevent infection. This is the same approach that was used to make the Ebola virus vaccine.

   * Non-replicating viral vector vaccine — Similar to replicating viral vector vaccines, a gene is inserted into a vector virus, but the vector virus does not reproduce in the vaccine recipient. Although the virus can’t make all of the proteins it needs to reproduce itself, it can make some proteins, including the COVID-19 spike protein. No currently licensed vaccines use this approach.

   * DNA vaccine — The gene that codes for the COVID-19 spike protein is inserted into a small, circular piece of DNA, called a plasmid. The plasmids are then injected as the vaccine. No currently licensed vaccines use this approach.

* mRNA vaccine — In this approach, the vaccine contains messenger RNA, called mRNA. mRNA is processed in cells to make proteins. Once the proteins are produced, the immune system will make a response against them to create immunity. In this case, the protein produced is the COVID-19 spike protein. No currently licensed vaccines use this approach.

Which type of COVID-19 vaccine is most likely to work?

       It is likely that more than one of these approaches will work, but until large clinical trials are completed, we won’t know for sure. Likewise, the different approaches may have different strengths and weaknesses. For example, mRNA or DNA vaccines are much faster to produce, but neither has been used to successfully make a vaccine that has been used in people.  On the other hand, killed viral vaccines and live, weakened viral vaccines have been used in people safely and effectively for many years, but they take longer to produce.

   In addition to differences in how long it takes to make different types of vaccines, each type may also cause the immune system to respond differently. Understanding the immune responses that are generated will be important for determining whether additional (booster) doses will be needed, how long vaccine recipients will be protected, and if one type offers benefits over another.

Is one of the COVID-19 vaccines expected be more effective for the elderly population?

     It is likely that COVID-19 vaccines could have different levels of effectiveness in various subgroups of people. Because the elderly generally do not respond as well to vaccines, one or more COVID-19 vaccines may not work well for them, which is concerning given their higher risk of severe disease. The large phase III studies may not include people over a certain age. But, the manufacturers have been encouraged to include older people, so that we have this type of information earlier in the process than may usually occur. We will have to wait and see what the data show to know which vaccine(s) work best in the older population.

How many doses of a COVID-19 vaccine will be needed? Will a booster dose be needed?

     The number of doses of a COVID-19 vaccine that will be needed has not yet been determined. The coronavirus vaccines being studied are evaluating one or two doses. When giving two doses, they are usually given one or two months apart. We will need to wait for the results of the clinical trials to have more information about how many doses will be needed.

How long will vaccine immunity last?

Since we do not yet know how long immunity after infection lasts, immunity following vaccination will also have to be determined. Likewise, immunity following vaccination will depend in part on which types of vaccines are licensed, what part of the immune system responds to the vaccine, and the level of immunity that is generated by the vaccine.

If more than one vaccine becomes available, could taking two different vaccines boost the effectiveness?

While it is likely that more than one COVID-19 vaccine will become available, we probably won’t have a good answer to this question until vaccines are actually licensed and we know more about them. Three scenarios can occur if a person is vaccinated with two versions of vaccines against the same disease, particularly close in time:

— They get a stronger immune response. An example of this was when children got inactivated polio vaccine and later got oral polio vaccine.

—- The second vaccine causes immunity that would be similar to receiving a second dose of the original vaccine. Using a different brand of hepatitis B vaccine for one or more doses would be an example of this.

— The immune response generated by the first vaccine interferes with components of the response to the second vaccine, in some cases causing lower immunity. For example, when people got a pneumococcal polysaccharide vaccine (PPSV) followed by a pneumococcal polysaccharide vaccine with a harmless helper protein attached to it, called pneumococcal conjugate vaccine (PCV), they had lower antibody responses to one part of the PCV vaccine than people who got the two vaccines in the opposite order (PCV followed by PPSV).

For these reasons, studies will need to be done to determine the effects of getting a second type of COVID-19 vaccine shortly after receiving a different one. If, however, we find that COVID-19 vaccines are like influenza vaccines and we need to get vaccinated annually, concerns about switching types from one year to the next are less likely to be an issue.

Will a coronavirus vaccine need to be given annually?

   When a vaccine is licensed, we will only have information about length of immunity for as long as we are from the trials. For example, if the first people in the study were vaccinated in July 2020 and the vaccine is licensed in December 2020, we will only have information about the immune response up to 5 months after vaccination. The vaccine manufacturer will likely continue to monitor vaccine recipients for several months or more, so that over time, we will continue to get a better picture of the durability of immunity. With this information, we will be better able to understand whether vaccines against COVID-19 will require annual dosing like influenza.

Is a coronavirus vaccine necessary?

   SARS-CoV-2 infections can be a minor hindrance or lead to severe disease or even death. While hygiene measures such as social distancing, handwashing, and wearing masks offer some help, the best way to stop this virus is to generate SARS-CoV-2-specific immunity. This specific immunity can be achieved in one of two ways — through illness or vaccination. Since illness could lead to severe disease or death, vaccination is a better alternative as long as safe and effective vaccines can be developed.

How long before a coronavirus vaccine takes effect?

   Generally speaking, it takes a week or two for immunity to develop following vaccination, but the specific timeline for any coronavirus vaccine will depend to some extent on which type of vaccine is licensed. For example, a live, weakened vaccine requires time to reproduce in the body, whereas an inactivated vaccine is given at a dose that will generate immunity. On the other hand, because the live, weakened vaccine reproduces to generate immunity, it might provide a more robust immune response than an inactivated vaccine

Bad Weather Brings Flu – Makes Sense

September 21, 2020 in Global Crisis Blog, Innovation Blog | Tags: , , , , | Leave a comment

Bad Weather Brings Flu – Makes Sense

By Shlomo Maital

 

The conflation of COVID-19 and the fall/winter influenza season worries public health officials. In Israel, hospitals are already over-stretched – and doctors and nurses dread the onslaught of flu patients, on top of several thousand new COVID-19 cases daily. This is why Israel is now in partial lockdown, during the High Holydays.

     A new study by a group of Israeli and Mideast scholars shows, for the Eastern Mediterranean, a close correlation between climate and flu. *

     The orange line above shows temperature. The red line: % of the population with flu. And the blue line: barometric pressure (inverted – high scale means low pressure). All three variables have been converted to a standardized zero to one normalized scale.

     So – what is the connection between weather and flu?

   It is pretty simple. Flu spreads through contact from one person to another. Outdoors, winds, even light breezes, disperse flu particles from sneezes and coughs and breathing. Indoors, this is far less true. In bad weather, people spend more time indoors.   Hence, more flu.

       This finding seems relevant for COVID-19 too. A friend of mine, a veteran pulmonary medical specialist, observes:

“With each cough and sneeze, there are very small particles under 10 microns in diameter, especially those under 2.5 microns, that tend to remain suspended in the air for a long time. This aerosol is scattered all over. While the volume of these particles is low, their surface area is large and lots of virus particles can stick to the surface of these small particles. It is now fully accepted that the virus’ transmission by aerosols is an important vector. The relatively large area of the eyes’ surface makes them vulnerable to the landing and culture of viruses. Protection against sprays and eye protection are crucial to creating barriers against contracting COVID-19.”

     “Cough is the dominant mode of spread and as such should be monitored in areas where people congregate to assess risk in an objective mode and to identify possible spreaders. Cough monitoring is feasible with devices being available and used in pulmonary and occupational contexts.”

        “The dilution in open air is immense. Consider the following example: A soft wind is blowing at 3.6 km/hour (2.2 miles per hour). If we consider a 4-meter- long test volume of air, the flow of air in the wind will sweep the test volume in four seconds, or nearly a thousand times per hour. This is significant and should be sufficient to prevent infection if very sporadic individuals are present. But if a distance of two meters cannot be observed at all times, the risk level is such that the use of a mask, at least surgical or cloth, is still required in the open.”

So, the message here is clear. We MUST get this second wave of COVID-19 under control before the flu season. If we don’t we will have two problems:

  • Bad weather will bring influenza, and some flu sufferers will need hospitalization
  • Bad weather will send people indoors, and COVID-19 spreads more easily there.

 

Hochman, A., Alpert, P., Negev, M., Abdeen, Z., Abdeen, A. M., Pinto, J. G., & Levine, H. (2020). The relationship between cyclonic weather regimes and seasonal influenza over the Eastern Mediterranean. Science of The Total Environment, 141686.

Ruth Bader Ginsburg – Words Matter

September 21, 2020 in Global Crisis Blog, Innovation Blog | Tags: , , , | Leave a comment

Ruth Bader Ginsburg – Words Matter

By Shlomo Maital

Ruth Bader Ginsburg in Israel

   Do words really matter?

   They do indeed. Especially when written by a diminutive Jewish woman, a Justice of the US Supreme Court for an entire generation.

   Ruth Bader Ginsburg said this, about her class with famous Russian novelist Vladimir Nabokov, at Cornell University: (from a blog by Frances Katz):

   “[Vladimir] Nabokov, changed the way I read and the way I write,” Ginsburg said. “Words could paint pictures, I learned from him. Choosing the right word, and the right word order, he illustrated, could make an enormous difference in conveying an image or an idea.”

   She also says she always employs several of the lessons she learned in his class: “I seek the right word and word order,” she explained. “ And I use the ‘read aloud’ test to check whether I have succeeded.”

   Rulings and dissenting opinions are first read aloud in court before being distributed to the public, so the ‘read aloud test’ helps her be certain the language be clear enough to articulate legal arguments but still be understood by ordinary citizens.

     Her use of language is clear and direct. She redefines the issue and makes her argument. She calls on those who agree with her to push for change. She did not call on Congress directly, use inflammatory language or rhetorical flourishes. She chose her words carefully to make sure there was no misunderstanding her call for action.

     One of her law clerks said yesterday on National Public Radio, that he worked hard on a legal opinion, and wrote 10 pithy pages. RBG complimented him, then took his draft and boiled it down to 3 and one half even more pithy pages, focused clear and powerful.

     Words to matter. RBG’s words changed America and the world. She used the phrase “gender discrimination”, not “sex discrimination”, because the latter phrase, she knew, would not speak to the male Justices.

     You CAN change the world, with the right words. And with stubborn persistence, and with, as she put it, the ability to “disagree without being disagreeable”.

Is COVID-19 Mutating? Yes – But Not Harmfully!

September 14, 2020 in Global Crisis Blog, Innovation Blog | Tags: , , , | Leave a comment

Is COVID-19 Mutating? Yes – But Not Harmfully!

By Shlomo Maital

   I’ve been worrying about whether the SARS-CoV-2 virus (the piece of RNA that gives people COVID-19) is mutating. Evolution is everywhere and inexorable, and it creates animals, insects and even viruses that are well adapted to survive and meet threats. So, I wondered, is the novel coronavirus mutating, to defeat our best efforts?

     The answer is no. Here are answers from Dr. Edward Holmes, an evolutionary virologist at University of Sydney, in today’s New York Times.*   I present his findings as Q&A:

  • “The coronavirus is mutating, and that’s fine (so far).” NYT Sept. 14, p. 11.

     Do viruses really mutate?

   “Viruses routinely mutate — and most of these changes are bad for the virus or even fatal, according to some studies. (A minority of mutations are neutral, and only a tiny minority beneficial.) The word “mutation” may sound ominous, but it is a humdrum fact of viral life and its implications most often aren’t nefarious for humans.”

   Has COVID-19 become more virulent, more dangerous?

   “ The real question is this: Has it become more virulent or more infectious than it was when it was first detected in Wuhan, central China, in December? The evidence suggests that it has not.   Like the viruses that give us influenza or measles, SARS-CoV-2 has a genetic code made up of RNA, or ribonucleic acid. But RNA is highly mutable, and since SARS-CoV-2 infects us by using our body’s cells to replicate itself again and again, every time its genome is copied, an error might creep in.   Most mutations are quickly lost, either by chance or because they damage some part of the virus’s main functions. Only a small proportion end up spreading widely or lasting. Mutation may be the fuel of evolution but, especially for an RNA virus, it also is just business as usual.”

 How fast is COVID-19 mutating?

     “RNA viruses tend to evolve rapidly — about a million times faster than human genes. Yet if SARS-CoV-2 stands out among them, it is for evolving more slowly than many: about five times less rapidly than the influenza viruses, for example.   According to Nextstrain, an open-source project that tracks the evolution of pathogens in real time, and other sources, SARS-CoV-2 is accumulating an average of about two mutations per month — which means that the forms of the virus circulating today are only about 15 mutations or so different from the first version traced to the outbreak in Wuhan.   To my knowledge, there is to date no evidence that SARS-CoV-2 has become more virulent or more lethal — nor, for that matter, that it has become less so.”

     Even if COVID-19 has not mutated to a more dangerous form, that kills more people – has it perhaps mutated to become more infectious – in a way Nature often does, to reproduce better? Is THIS perhaps why the coronavirus has created strong second waves in many countries?

   “I do not believe that the evolution of SARS-CoV-2 is what’s driving the virus’s continued spread. The coronavirus remains good at propagating itself because most of us still are susceptible to it; we are not immune, and it can still find new hosts to infect relatively easily.”

Are you sure?

“There has been much discussion over whether the D614G mutation — which affects the so-called spike protein of the virus — has made SARS-CoV-2 more infectious. The spike protein sits on the surface of the coronavirus, and it matters because it’s the part of the virus that attaches to the host’s cells. “D614G” is shorthand for a change at position 614 of the spike protein, from an aspartic acid (D) to a glycine amino acid (G). (The technical literature refers to “D614” as the earlier configuration and “G614” as the later one.)   The D614G mutation, which probably initially arose in China, first appeared to become more and more frequent in the outbreak in northern Italy in February. The G614 form of the virus has since spread all over the world and has become the dominant variant.   The D614G mutation does seem to have increased the infectivity of the coronavirus — at least in cells grown in laboratories, according to a recent paper by the computational biologist Bette Korber and others published in the journal Cell.”

“Apparently based partly on this and other studies, health authorities in various countries have claimed that the G614 form of the coronavirus may be 10 times more infectious than the version first detected in Wuhan.   But as some epidemiologists have warned, it is difficult, not to mention unwise, to extrapolate from lab results to explain how the virus actually spreads in a real population.   In the issue of Cell …. the viral epidemiologist Nathan Grubaugh and colleagues argued that the “increase in the frequency of G614 could be explained by chance and the epidemiology of the pandemic.”

Bottom line?

         “For now, though, SARS-CoV-2 essentially is the same virus that emerged in December. Sure, it has mutated, but not, so far, in ways that should change how scientists think about how to tackle it — and not in ways that should worry you.”

 

 

How Warsaw Ghetto Jews Controlled a Typhus Epidemic: Lessons for Today

September 12, 2020 in Global Crisis Blog, Innovation Blog | Tags: , , , , , | Leave a comment

How Warsaw Ghetto Jews Controlled a Typhus Epidemic:

Lessons for Today

By Shlomo Maital  

 

   

                                                                                 Typhus bacteria

   This is the story of how 450,000 Warsaw Jews, crammed by the Nazis into a tiny ghetto 3.2 km. sq. (about 2 miles square, roughly Central Park) – starting in Nov. 1940 — and saw a typhus epidemic spread, with several thousand cases.. and then, by July 1942, totally flattened the curve and eradicated the epidemic. Right at that time, late 1942, the Nazis assaulted the ghetto, and despite valiant but futile resistance, destroyed the ghetto and transported its residents to Treblinka extermination camp, where more than  280,000 were killed.

So – what exactly is typhus, and how did the Warsaw Ghetto Jews flatten the curve?

   Typhus is a group of infectious diseases —   Common symptoms include fever, headache, and a rash. Typically these begin one to two weeks after exposure. The diseases are caused by specific types of bacterial infection. Epidemic typhus is due to Rickettsia prowazekii spread by body lice.

   In a just-published article in Science Advances, theoretical biologist Lewi Stone and colleagues describe the Warsaw ghetto typhus epidemic, and how it was flattened (see graph above).

In brief: Among the Jewish doctors imprisoned by the Nazis in the ghetto were several distinguished epidemiologists, including one nominated for a Nobel Prize. The doctors told inhabitants to keep apart, and as far as possible practice body hygiene (the human body louse spreads the disease).

The ghetto inhabitants respected and trusted the doctors and did what they said. Authors of the study conclude: “Strangely, the epidemic was curtailed and was brought to a sudden halt before winter, when typhus normally accelerates. A far more massive epidemic outbreak was prevented through the antiepidemic efforts by the often considered incompetent and corrupt ghetto leadership and the Herculean efforts of ghetto doctors.

So – the starving inhabitants, weakened by hunger, lacking water, packed into housing like sardines — did manage to ‘flatten the curve’, almost to zero, at a time when typhus epidemics had ravaged and killed many, in other locations.

The question arises: If they could, if they did – why in the world can’t we? Why aren’t we?

  • Extraordinary curtailment of massive typhus epidemic in the Warsaw Ghetto Lewi Stone, Daihai He, Stephan Lehnstaedt and Yael Artzy-Randrup. Science Advances, ci Adv 6 (30), eabc0927. DOI: 10.1126/sciadv.abc0927   Feb 2020

 

2,000-year-old dates: Delicious! Yum!

September 9, 2020 in Global Crisis Blog, Innovation Blog | Tags: , , , , | Leave a comment

2,000-year-old dates: Delicious! Yum!

By Shlomo Maital

  

Credit: Dan Ballity, The New York Times

  My story today begins nearly 2,000 years ago – around 73 CE — as Roman legions put a small group of die-hard 960 Jewish rebels under siege, in Masada, a mountaintop near the Dead Sea. The rebels commit suicide, every single one, rather than be taken prisoner by the Romans.

   Archaeologist Prof. Ehud Netzer, excavating at Masada, is reported (according to the San Francisco Chronicle, in 2005) to discover data palm seeds, genus Phoenix dactylifera, discarded in a corner.

     The ancient 2,000-year-old seeds are given to a botanist, Dr. Elaine Solowey, at the Arava Institute, located at Kibbutz Ketura, founded in 1973, in the Arava Valley north of Eilat.  Solowey is the author of Supping at God’s Table: A Handbook for the Domestication of Wild Trees for Food and Fodder. Solowey and her colleagues embark on a Don Quixote mission: To germinate the seeds, grow them into a date palm tree – and harvest the fruit.

     Really??? After two millenia?

     Solowey treats the seeds with a growth hormone, gibberellic acid, researched at Yale in the 1960’s. The seeds are planted on Jan. 26, 2005. Amazingly, within five weeks, a seed sprouts to form a small tree! It is given a name: Methuselah Palm, after Methuselah, the son of Enoch, the father of Lamech, and the grandfather of Noah, in the Bible. Methuselah lived 969 years, the longest-lived person in the Bible. A good name!

     Fast forward: New York Times correspondent Isabel Kershner reports in the Times, Sept. 8, p. 3, this:

“The plump golden-brown dates hanging in a bunch just above the sandy soil were ready to pick…..’They are beautiful!’ exclaimed Dr. Sarah Sallon [a medical doctor, from Hadassah Hospital, genetics expert, natural medicine researcher and part of the team], with the elation of a new mother, as each date, its skin slightly wrinkled, was plucked gently off its stem at a sunbaked kibbutz in southern Israel. ..They were tasty, too, with a fresh flavor that gave no hint of their two-millenium incubation period. The honey-blond, semi-dry flesh had a fibrous, chewy texture and a subtle sweetness.     …These were the much-extolled, but long-lost Judean dates, and the harvest this month was hailed as a modern miracle of science.”

For Jews, it is possible one day to eat the same dates that the Masada rebels ate. For Christians, perhaps one day they will eat the same dates, the same flavor, texture, color, appearance, Judean dates, that Jesus ate.

And for the world — when the pandemic has made human civilization seem fragile, bumbling, and in great danger, we learn from the 2,000 year old dates how durable, adaptable and resilient Nature is, in its quest to endure and to prevail.   And, as a footnote, how scientists can also prevail in quixotic quests that literally bear fruit.

For those who want to learn about the science see this article:

Sallon, S., Cherif, E., Chabrillange, N., Solowey, E., Gros-Balthazard, M., Ivorra, S., … & Aberlenc, F. (2020). Origins and insights into the historic Judean date palm based on genetic analysis of germinated ancient seeds and morphometric studies. Science advances, 6(6), eaax0384.

     

Blog entries written by Prof. Shlomo Maital

Shlomo Maital

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