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Prof. Amnon Shashua: From Mobileye to COVID-19

By Shlomo Maital

Prof. Amnon Shashua

    Many years ago, Hebrew University Computer Science Professor Amnon Shashua attended a computer vision conference in Europe. Automobile executives there asked him, how many cameras are needed on a car, to warn of danger? The prevailing wisdom: at least two, because we need two eyes for depth perception (through ‘triangulation’). Shashua said, no, we need just one camera. It can measure depth by comparing data at two points in time…   The executives scoffed. Shashua came home to Israel, and launched Mobileye, which saves lives through its little camera and sophisticated software. Mobileye was acquired by Intel for $15 b. Shashua continues to head it.  

     With the outbreak of COVID-19, Prof. Shashua has tackled the issue of strategy.   His claim: Mathematics has the answer. In the online magazine Medium, he and Shai Shalev-Shwartz have published their mathematical analysis of three different strategies, and they recommend one of them. The title asks the key question: “Can we contain COVID-19 without locking down?”.   Here is a summary. *

     “We present an analysis of a risk-based selective quarantine model where the population is divided into low and high-risk groups. The high-risk group is quarantined until the low-risk group achieves herd-immunity. We tackle the question of whether this model is safe, in the sense that the health system can contain the number of low-risk people that require severe ICU care (such as life support systems).

   “ One could consider three models for handling the spread of Covid-19.

*   Risk-based selective Quarantine: Divide the population into two groups, low-risk and high-risk. Quarantine the high-risk and gradually release the low-risk population to achieve a managed herd immunity of that population.

*   Containment-based selective quarantine: Find all the positive cases and put them in quarantine. This requires an estimation of the “contagious time interval” per age group, then given this time interval one could recursively isolate all the individuals at risk from a person that is carrying the virus using “contact tracing”. Another tool is predictive testing using contact-tracing to identify people with many contacts with other people and perform tests on them.

* Countrywide (or region-wide) lock-down until the spread of the virus is under control. The lock-down could take anywhere from weeks to months. This is the safest route but does not prevent a “second wave” from occurring.

     “In the event a risk-based quarantine approach would be contemplated by decision-makers, the purpose of this document is to provide decision-makers a formal and tight bounds to investigate whether the health system can cope with the number of severe cases that would reach ICU. Embedded in the reasoning is the idea of selective quarantine (based on age groups and existing pre-conditions, but could be any other criteria) where the ”high-risk” group (the one we suspect will have a high rate of severe cases) is quarantined and the other is allowed to spread the virus under certain distancing protocols. The underlying premise is that a full population-wide quarantine is not a solution in itself — it is merely a step to buy time followed by a more managed (non brute-force) approach. The managed phase underlying our thinking is to create herd immunity of the low-risk group in a controlled manner while keeping the economy going. It is all about keeping the health system in check and not overwhelming its capacity to handle severe cases. The question we ask in this document is whether we can estimate in advance, through sampling, that the number of severe cases arising from the low-risk group would not overwhelm the system?

   “…When the high-risk group is released from isolation they would be facing a largely immune population thus naturally facing a very slow spread of infection with a good chance to whither the storm until a cure or vaccine is available. 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 still the mortality of the high-risk group is likely to be higher than the risk-based model.”

     This model has been proposed before by Nobel Laureate Paul Krugman (see my blog on his proposal, April 2).   Shashua serves on an advisory board in Israel, advising Health Ministry officials. I believe his ideas are being implemented, though cautiously.

     Warning: the article whose URL is given below can be dangerous to your health; it is highly mathematical.

*   https://medium.com/amnon-shashua/can-we-contain-covid-19-without-locking-down-the-economy-2a134a71873f

 

Defeating COVID-19’s Attack on Our Lungs:

A Preemies’ Treatment Migrates to Adults

By Shlomo Maital

Prof. Josué Sznitman and Dr. Ostrovski, Technion

   In a previous blog, Dr. Richard Levitan explained how COVID-19 attacks the lungs: “The coronavirus attacks lung cells that make surfactant. This substance helps the air sacs in the lungs stay open between breaths and is critical to normal lung function. As the inflammation from Covid pneumonia starts, it causes the air sacs to collapse, and oxygen levels fall.”  

     Current treatment often involves use of ventilators. But the results are not impressive. Between 50% and 70% of those put on ventilators do not survive.

     Two Technion Biomedical Engineering Faculty researchers, Prof. Josué Sznitman and Dr. Ostrovski, have been working for years on a way to help babies born prematurely, who have ARDS (acute respiratory distress syndrome), to breathe better and recover. Their problem? Lack of surfactant, crucial for the lungs’ functioning.

     Sznitman notes that for 30 years now, we have known that injecting surfactant directly into neonates’ (preemies’) lungs “greatly helps their lungs function”. The success rate, he notes, is as high as 98%!

     So, Sznitman wondered, why not inject surfactant into the lungs of suffering COVID-19 patients? Not so simple. “Instillations in larger lungs quickly gather in pools, drowning some parts of the lungs and depriving others of the surfactant”, he explained to Haaretz reporter Asaf Ronel.

       Solution? Turn the liquid surfactant into foam. “Foam has more volume than liquid, and is less affected by gravity. So it can be spread in a uniform manner throughout the lungs and restore the ‘facelift’ to the epithelial cells that [lungs] need to function properly”, he explained. Tests with rats have been highly successful. Next month preclinical trials begin with pigs.

     I wish this treatment could be speeded up and fast-tracked. I think it could save many lives.

A Vaccine for Ordinary Flu?

By Shlomo Maital

Professor Ruth Arnon, Weizmann Institute

With the world’s attention singularly focused on COVID-19 (understandably), another threat waits in the wings – ordinary flu.

   Each fall, my wife and I take a number at our HMO and get a flu shot. The flu shot is different each year, because each year the flu virus is different, having mutated over the previous months. The flu vaccine itself is an educated guess, guessing at which flu will be most virulent several months later. Sometimes the guess works, sometimes it is quite wrong.  

   Every year it is estimated that 5 million people get the common flu, and kills up to 650,000 people, according to the World Health Organization.  This fall will be no different. People weakened by common flu may be more susceptible to COVID-19, which will doubtless linger. So we do need to worry about common flu, not just COVID-19.

     Weizmann Institute is a leading research university in Rehovot, Israel. Many years ago, Prof. Ruth Arnon discovered copaxone, a drug effective in treating those with multiple sclerosis (MS). The drug was developed and marketed by Teva, an Israeli pharma company.

       Ruth Arnon is 86 years old, and continues to work hard in her lab. A headline in the April 28 issue of The Marker, an Israeli business daily, features some startling news: Arnon’s flu vaccine, developed and tested by BiondVax, a startup, is going into Phase 3 clinical trials (the final phase).

       What is different about Arnon’s flu shot is this: It works (IF it works, and it seems that it does) against ALL flu viruses. So we will need just one shot, like mumps and measles vaccine, and not new shots every fall.

       How does Arnon’s vaccine work? Arnon: “We studied the proteins of the flu virus. We identified four places in flu viruses that are common to every type of flu”. The vaccine Arnon developed and patented, and which is under clinical trials through BiondVax, works to block the parts of the flu proteins common to all varieties.

       Arnon notes cautiously that so far it has given flu immunity to mice, genetically engineered to resemble human genes. And the vaccine is approaching the finish line of this long long marathon, Phase 3.   If it can be manufactured fast enough, and cheaply enough, perhaps it will save the world many deaths from flu and flu-weakened coronavirus patients.

     Now, let’s be clear. COVID-19 is NOT flu. Arnon’s vaccine will not affect coronavirus. But if it saves deaths from common flu, and flu-related COVID-19, it can save many many thousands of lives. So we will track the BiondVax vaccine carefully, as it completes Phase 3.

Getting Ahead of COVID-19: Dr. Levitan’s Wisdom

By Shlomo Maital

Dr. Richard Levitan, holding a pulse oximeter

    Dr. Richard Levitan is an emergency medicine doctor, specializing in respiration, and normally practices medicine at a small hospital in Littleton Regional Healthcare, Littleton, New Hampshire. When the coronavirus pandemic broke out, he volunteered to help doctors at Bellevue Hospital in New York City, where he once trained.

   He has many valuable insights on how we must change the way we treat this disease, based on his professional experience and knowledge, and on what he saw at Bellevue. His article appears on CNN’s website. Here is a short version. Again, I apologize for this 1,850 word blog… but I felt all Levitan’s words were important.

     The bottom line: Use a simple device, an oximeter, to detect when oxygen levels are low, indicating virus distress, and start THEN to treat the patient, long before a ventilator is needed. The body adjusts, and breathes more rapidly, so often people ill with coronavirus do not call for medical help until they are very far gone and their lungs have serious pneumonia.   Many do not recover even when ventilated, and those that do, often need dialysis or have blood clots.

   ….

   “I have been practicing emergency medicine for 30 years. In 1994 I invented an imaging system for teaching intubation, the procedure of inserting breathing tubes. This led me to perform research into this procedure, and subsequently teach airway procedure courses to physicians worldwide for the last two decades.

   “So at the end of March, as a crush of Covid-19 patients began overwhelming hospitals in New York City, I volunteered to spend 10 days at Bellevue, helping at the hospital where I trained. Over those days, I realized that we are not detecting the deadly pneumonia the virus causes early enough and that we could be doing more to keep patients off ventilators — and alive.

   “On the long drive to New York from my home in New Hampshire, I called my friend Nick Caputo, an emergency physician in the Bronx, who was already in the thick of it. I wanted to know what I was facing, how to stay safe and what his insights into airway management with this disease were. “Rich,” he said, “it’s like nothing I’ve ever seen before.”

     “He was right. Pneumonia caused by the coronavirus has had a stunning impact on the city’s hospital system. Normally an E.R. has a mix of patients with conditions ranging from the serious, such as heart attacks, strokes and traumatic injuries, to the non-life-threatening, such as minor lacerations, intoxication, orthopedic injuries and migraine headaches.

     “During my recent time at Bellevue, though, almost all the E.R. patients had Covid pneumonia. Within the first hour of my first shift I inserted breathing tubes into two patients.   Even patients without respiratory complaints had Covid pneumonia. The patient stabbed in the shoulder, whom we X-rayed because we worried he had a collapsed lung, actually had Covid pneumonia. In patients on whom we did CT scans because they were injured in falls, we coincidentally found Covid pneumonia. Elderly patients who had passed out for unknown reasons and a number of diabetic patients were found to have it.

   “And here is what really surprised us: These patients did not report any sensation of breathing problems, even though their chest X-rays showed diffuse pneumonia and their oxygen was below normal. How could this be?   We are just beginning to recognize that Covid pneumonia initially causes a form of oxygen deprivation we call “silent hypoxia” — “silent” because of its insidious, hard-to-detect nature.

   “Pneumonia is an infection of the lungs in which the air sacs fill with fluid or pus. Normally, patients develop chest discomfort, pain with breathing and other breathing problems. But when Covid pneumonia first strikes, patients don’t feel short of breath, even as their oxygen levels fall. And by the time they do, they have alarmingly low oxygen levels and moderate-to-severe pneumonia (as seen on chest X-rays). Normal oxygen saturation for most persons at sea level is 94 to 100 percent; Covid pneumonia patients I saw had oxygen saturations as low as 50 percent.

     “To my amazement, most patients I saw said they had been sick for a week or so with fever, cough, upset stomach and fatigue, but they only became short of breath the day they came to the hospital. Their pneumonia had clearly been going on for days, but by the time they felt they had to go to the hospital, they were often already in critical condition.

     “In emergency departments we insert breathing tubes in critically ill patients for a variety of reasons. In my 30 years of practice, however, most patients requiring emergency intubation are in shock, have altered mental status or are grunting to breathe. Patients requiring intubation because of acute hypoxia are often unconscious or using every muscle they can to take a breath. They are in extreme duress. Covid pneumonia cases are very different.

     “A vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage — seemingly incompatible with life — but they were using their cellphones as we put them on monitors. Although breathing fast, they had relatively minimal apparent distress, despite dangerously low oxygen levels and terrible pneumonia on chest X-rays.

     “We are only just beginning to understand why this is so. The coronavirus attacks lung cells that make surfactant. This substance helps the air sacs in the lungs stay open between breaths and is critical to normal lung function. As the inflammation from Covid pneumonia starts, it causes the air sacs to collapse, and oxygen levels fall. Yet the lungs initially remain “compliant,” not yet stiff or heavy with fluid. This means patients can still expel carbon dioxide — and without a buildup of carbon dioxide, patients do not feel short of breath.

   “Patients compensate for the low oxygen in their blood by breathing faster and deeper — and this happens without their realizing it. This silent hypoxia, and the patient’s physiological response to it, causes even more inflammation and more air sacs to collapse, and the pneumonia worsens until oxygen levels plummet. In effect, patients are injuring their own lungs by breathing harder and harder. Twenty percent of Covid pneumonia patients then go on to a second and deadlier phase of lung injury. Fluid builds up and the lungs become stiff, carbon dioxide rises, and patients develop acute respiratory failure.

     “By the time patients have noticeable trouble breathing and present to the hospital with dangerously low oxygen levels, many will ultimately require a ventilator. Silent hypoxia progressing rapidly to respiratory failure explains cases of Covid-19 patients dying suddenly after not feeling short of breath. (It appears that most Covid-19 patients experience relatively mild symptoms and get over the illness in a week or two without treatment.)

     “A major reason this pandemic is straining our health system is the alarming severity of lung injury patients have when they arrive in emergency rooms. Covid-19 overwhelmingly kills through the lungs. And because so many patients are not going to the hospital until their pneumonia is already well advanced, many wind up on ventilators, causing shortages of the machines. And once on ventilators, many die.

     “Avoiding the use of a ventilator is a huge win for both patient and the health care system. The resources needed for patients on ventilators are staggering. Vented patients require multiple sedatives so that they don’t buck the vent or accidentally remove their breathing tubes; they need intravenous and arterial lines, IV medicines and IV pumps. In addition to a tube in the trachea, they have tubes in their stomach and bladder. Teams of people are required to move each patient, turning them on their stomach and then their back, twice a day to improve lung function.

   “There is a way we could identify more patients who have Covid pneumonia sooner and treat them more effectively — and it would not require waiting for a coronavirus test at a hospital or doctor’s office. It requires detecting silent hypoxia early through a common medical device that can be purchased without a prescription at most pharmacies: a pulse oximeter.

   “Pulse oximetry is no more complicated than using a thermometer. These small devices turn on with one button and are placed on a fingertip. In a few seconds, two numbers are displayed: oxygen saturation and pulse rate. Pulse oximeters are extremely reliable in detecting oxygenation problems and elevated heart rates.

   “Pulse oximeters helped save the lives of two emergency physicians I know, alerting them early on to the need for treatment. When they noticed their oxygen levels declining, both went to the hospital and recovered (though one waited longer and required more treatment). Detection of hypoxia, early treatment and close monitoring apparently also worked for Boris Johnson, the British prime minister.

     “Widespread pulse oximetry screening for Covid pneumonia — whether people check themselves on home devices or go to clinics or doctors’ offices — could provide an early warning system for the kinds of breathing problems associated with Covid pneumonia. People using the devices at home would want to consult with their doctors to reduce the number of people who come to the E.R. unnecessarily because they misinterpret their device. There also may be some patients who have unrecognized chronic lung problems and have borderline or slightly low oxygen saturations unrelated to Covid-19.

     “All patients who have tested positive for the coronavirus should have pulse oximetry monitoring for two weeks, the period during which Covid pneumonia typically develops. All persons with cough, fatigue and fevers should also have pulse oximeter monitoring even if they have not had virus testing, or even if their swab test was negative, because those tests are only about 70 percent accurate. A vast majority of Americans who have been exposed to the virus don’t know it.

   “There are other things we can do as well to avoid immediately resorting to intubation and a ventilator. Patient positioning maneuvers (having patients lie on their stomach and sides) open up the lower and posterior lungs most affected in Covid pneumonia. Oxygenation and positioning helped patients breathe easier and seemed to prevent progression of the disease in many cases. In a preliminary study by Dr. Caputo, this strategy helped keep three out of four patients with advanced Covid pneumonia from needing a ventilator in the first 24 hours.

   “To date, Covid-19 has killed more than 40,600 people nationwide — more than 10,000 in New York State alone. Oximeters are not 100 percent accurate, and they are not a panacea. There will be deaths and bad outcomes that are not preventable. We don’t fully understand why certain patients get so sick, or why some go on to develop multi-organ failure. Many elderly people, already weak with chronic illness, and those with underlying lung disease do very poorly with Covid pneumonia, despite aggressive treatment.

   “But we can do better. Right now, many emergency rooms are either being crushed by this one disease or waiting for it to hit. We must direct resources to identifying and treating the initial phase of Covid pneumonia earlier by screening for silent hypoxia.

     “It’s time to get ahead of this virus instead of chasing it.”

 

Why New York Dropped the Ball – Part Two

By Shlomo Maital

In my previous blog, I quoted Charles Duhigg, The New Yorker, who explored why Seattle escaped the “valley of virus death”, largely, while New York City foundered in it. I focused on what Seattle did right. Now, I would like to share with you what New York City did wrong. You guessed it – it has to do with politicians, who feud.

[Special thanks to New Yorker for freely sharing all their great reporting on COVId-19].

And…once again, it is long – 2,500 words. But I think worth reading.

   “The initial coronavirus outbreaks in New York City emerged at roughly the same time as those in Seattle. But the cities’ experiences with the disease have markedly differed. By the second week of April, Washington State had roughly one recorded fatality per fourteen thousand residents. New York’s rate of death was nearly six times higher.

   “There are many explanations for this divergence. New York is denser than Seattle and relies more heavily on public transportation, which forces commuters into close contact. In Seattle, efforts at social distancing may have been aided by local attitudes—newcomers are warned of the Seattle Freeze, which one local columnist compared to the popular girl in high school who “always smiles and says hello” but “doesn’t know your name and doesn’t care to.” New Yorkers are in your face, whether you like it or not. (“Stand back at least six feet, playa,” a sign in the window of a Bronx bodega cautioned. “COVID-19 is some real shit!”) New York also has more poverty and inequality than Seattle, and more international travellers. Moreover, as Mike Famulare, a senior research scientist at the Institute for Disease Modeling, put it to me, “There’s always some element of good luck and bad luck in a pandemic.”

   “It’s also true, however, that the cities’ leaders acted and communicated very differently in the early stages of the pandemic. Seattle’s leaders moved fast to persuade people to stay home and follow the scientists’ advice; New York’s leaders, despite having a highly esteemed public-health department, moved more slowly, offered more muddied messages, and let politicians’ voices dominate.

     “New York’s mayor, Bill de Blasio, has long had a fraught relationship with the city’s Department of Health and Mental Hygiene, which, though technically under his control, seeks to function independently and avoid political fights. “There’s always a bit of a split between the political appointees, whose jobs are to make a mayor look good, and public-health professionals, who sometimes have to make unpopular recommendations,” a former head of the Department of Health told me. “But, with the de Blasio people, that antagonism is ten times worse. They are so much more impossible to work with than other administrations.” In 2015, when Legionnaires’ disease sickened at least a hundred and thirty New Yorkers and killed at least twelve, tensions between de Blasio and the Health Department came to a head. After de Blasio ordered health officials to force their way into buildings in the Bronx to test cooling towers for contamination, even though the outbreak’s source had already been identified, the officials complained that the Mayor was wasting their time in order to brag to reporters that he’d done everything possible to stamp out the disease. When the deputy commissioner for environmental health, Daniel Kass, refused City Hall’s demands, one of the city’s deputy mayors urged the commissioner of health, Mary Bassett, to fire Kass. She ignored the suggestion, but Kass eventually resigned. He later told colleagues he felt that his rebellion had made coöperation with City Hall impossible.

   “Dan Kass is one of the best environmental-health experts in the country,” Bassett, who now teaches at Harvard, said. “New York has one of the best health departments in the United States, possibly the world. We’d all be better off if we were listening really closely to them right now.”

   “In early March, as Dow Constantine was asking Microsoft to close its offices and putting scientists in front of news cameras, de Blasio and New York’s governor, Andrew Cuomo, were giving speeches that deëmphasized the risks of the pandemic, even as the city was announcing its first official cases. De Blasio initially voiced caution, saying that “no one should take the coronavirus situation lightly,” but soon told residents to keep helping the city’s economy. “Go on with your lives + get out on the town despite Coronavirus,” he tweeted on March 2nd—one day after the first COVID-19 diagnosis in New York. He urged people to see a movie at Lincoln Center. On the day that Seattle schools closed, de Blasio said at a press conference that “if you are not sick, if you are not in the vulnerable category, you should be going about your life.” Cuomo, meanwhile, had told reporters that “we should relax.” He said that most infected people would recover with few problems, adding, “We don’t even think it’s going to be as bad as it was in other countries.”

     “De Blasio’s and Cuomo’s instincts are understandable. A political leader’s job, in most situations, is to ease citizens’ fears and buoy the economy. During a pandemic, however, all those imperatives are reversed: a politician’s job is to inflame our paranoia, because waiting until we can see the danger means holding off until it’s too late. The city’s epidemiologists were horrified by the comforting messages that de Blasio and Cuomo kept giving. Jeffrey Shaman, a disease modeller at Columbia, said, “All you had to do was look at the West Coast, and you knew it was coming for us. That’s why Seattle and San Francisco and Portland were shutting things down.” But New York “dithered instead of telling people to stay home.”

   “By early March, the city’s Department of Health had sent the Mayor numerous proposals on fighting the virus’s spread. Since there weren’t enough diagnostic kits to conduct extensive testing, public-health officials proposed “sentinel surveillance”: asking local hospitals to provide the Department of Health with swabs collected from people who had flulike symptoms and had tested negative for influenza. By testing a selection of those swabs, the department could estimate how rapidly and widely the coronavirus was moving through the city. In previous outbreaks, such studies had been tremendously useful in guiding governmental responses—and this spring Los Angeles effectively deployed the strategy, as did Santa Clara County, in California, and the state of Hawaii.

“In New York City, the Health Department began collecting swabs, but the initiative met swift resistance. Under federal health laws, such swabs have to be anonymized for patients who haven’t consented to a coronavirus test. This meant that, even if city officials learned that many people were infected, officials wouldn’t be able to identify, let alone warn, any of them. The Mayor’s office refused to authorize testing the swabs. “They didn’t want to have to say, ‘There are hundreds, maybe thousands, of you who are positive for coronavirus, but we don’t know who,’ ” a Department of Health official told me, adding, “It was a real opportunity to communicate to New Yorkers that this is serious—you have to stay home.” The effort was blocked over fears that it might create a panic, but such alarm might have proved useful. After all, the official told me, panic is pretty effective at getting people to change their behavior. Instead, the Mayor’s office informed the Health Department that the city would sponsor a job fair to find a few new “disease detectives.” That event was held on March 12th, in Long Island City. The Department of Health official said, “We’re in the middle of a catastrophe, and their solution is to make us waste time interviewing and onboarding people!” (The Mayor’s office eventually relented on the sentinel-surveillance samples, and testing began on March 23rd—almost a month after samples were first collected. By then, the outbreak was well under way.)

     “As New York City schools, bars, and restaurants remained open, relations between the Department of Health and City Hall devolved. Health supervisors were “very, very angry,” one official told me. In particular, health officials were furious that de Blasio kept telling New Yorkers to go out and get a test if they suspected they were infected. On March 4th, he tweeted, “If you feel flu-like symptoms (fever, cough and shortness of breath), and recently traveled to an area affected by coronavirus . . . go to your doctor.” This was the opposite of what city health supervisors were advising: people needed to stay inside and call their doctor if they felt sick. Making trips to doctors’ offices or emergency rooms only increased the odds that the virus would spread, and the city’s limited supply of tests needed to be saved for people with life-threatening conditions. De Blasio’s staff, however, had started micromanaging the department’s communications, including on Twitter. Finally, on March 15th, the Department of Health was allowed to post a thread: “If you are sick, STAY HOME. If you do not feel better in 3 to 4 days, consult with your health care provider”; “Testing should only be used for people who need to be hospitalized”; “Everyone in NYC should act as if they have been exposed to coronavirus. . . . New Yorkers who are not sick should also stay home as much as possible.” One City Council member told me that health officials “had been trying to say that publicly for weeks, but this mayor refuses to trust the experts—it’s mind-boggling.”

   “As the city’s scientists offered plans for more aggressive action and provided data showing that time was running out, the Mayor’s staff responded that the health officials were politically naïve. At one point, Dr. Marcelle Layton, the city’s assistant commissioner of communicable diseases, and an E.I.S. alum who is revered by health officials across the nation for her inventiveness and dedication, was ordered to City Hall, in case she was needed to help the Mayor answer questions from the press. She sat on a bench in a hallway for three hours, away from her team, while politicians spoke to the media. (Layton declined interview requests.) At press conferences, Layton and other physicians played minimal roles while de Blasio and Cuomo, longtime rivals, each attempted to take center stage. The two men even began publicly feuding—arguing in the press, and through aides, about who had authority over schools and workplace closures.

   “Eventually, three of the top leaders of the city’s Department of Health met with de Blasio and demanded that he quickly instate social-distancing rules and begin sending clear messages to the public to stay indoors. Layton and a deputy health commissioner, Dr. Demetre Daskalakis, indicated to de Blasio’s staff that if the Mayor didn’t act promptly they would resign. (The next day, Layton’s staff greeted her with applause, and at least one employee offered to give her some money if she had to make good on the ultimatum.) De Blasio was in a corner: he had long positioned himself as a champion of the underclass, and closing schools would disproportionately hurt the poor and vulnerable. What’s more, unions representing health-care workers had threatened that nurses, orderlies, and others might stay home unless there was a plan to provide child care.

     “Nevertheless, de Blasio finally acceded to the health officials’ demands. On March 16th, after a compromise was reached with the health-care unions, city schools were closed, and Cuomo ordered all gyms and similar facilities to shut down. The messaging remained jumbled, however. Right before the gym closure was set to take effect, de Blasio asked his driver to take him to the Y.M.C.A. in Park Slope, near his old home, for a final workout. Even de Blasio’s allies were outraged. A former adviser tweeted, “The mayor’s actions today are inexcusable and reckless.” Another former consultant tweeted that the gym visit was “Pathetic. Self-involved. Inexcusable.”

     “De Blasio and Cuomo kept bickering. On March 17th, de Blasio told residents to “be prepared right now for the possibility of a shelter-in-place order.” The same day, Cuomo told a reporter, “There’s not going to be any ‘you must stay in your house’ rule.” Cuomo’s staff quietly told reporters that de Blasio was acting “psychotic.” Three days later, though, Cuomo announced an executive order putting the state on “pause”—which was essentially indistinguishable from stay-at-home orders issued by cities in Washington State, California, and elsewhere. (A spokesperson for de Blasio said that City Hall’s “messaging changed as the situation and the science changed” and that there was “no dithering.” A spokesperson for Cuomo said that “the Governor communicated clearly the seriousness of this pandemic” and that “the Governor has been laser focused on communicating his actions in a way that doesn’t scare people.”)

   “To a certain extent, de Blasio’s and Cuomo’s tortured delays make sense. Good politicians should worry about poor children missing school just as much as they worry about the threat of an emerging disease. “That’s why E.I.S. training is so important,” Sonja Rasmussen, a former C.D.C. official, told me. In a pandemic, “the old ways of thinking get flipped around.” She added, “You have to make the kinds of choices that, if you aren’t trained for them, are really hard to make. And there’s no time to learn from your mistakes.”

   “Today, New York City has the same social-distancing policies and business-closure rules as Seattle. But because New York’s recommendations came later than Seattle’s—and because communication was less consistent—it took longer to influence how people behaved. According to data collected by Google from cell phones, nearly a quarter of Seattleites were avoiding their workplaces by March 6th. In New York City, another week passed until an equivalent percentage did the same. Tom Frieden, the former C.D.C. director, has estimated that, if New York had started implementing stay-at-home orders ten days earlier than it did, it might have reduced COVID-19 deaths by fifty to eighty per cent. Another former New York City health commissioner told me that “de Blasio was just horrible,” adding, “Maybe it was unintentional, maybe it was his arrogance. But, if you tell people to stay home and then you go to the gym, you can’t really be surprised when people keep going outside.”

   “More than fifteen thousand people in New York are believed to have died from COVID-19. Last week in Washington State, the estimate was fewer than seven hundred people. New Yorkers now hear constant ambulance sirens, which remind them of the invisible viral threat; residents are currently staying home at even higher rates than in Seattle. And de Blasio and Cuomo—even as they continue to squabble over, say, who gets to reopen schools—have become more forceful in their warnings. Rasmussen said, “It seems silly, but all these rules and SOHCOs and telling people again and again to wash their hands—they make a huge difference. That’s why we study it and teach it.” She continued, “It’s really easy, with the best of intentions, to say the wrong thing or send the wrong message. And then more people die.”

 

Why Seattle Saved Lives – and New York City Did Not!

By Shlomo Maital

   In “The Pandemic Protocol”, The New Yorker, By Charles Duhigg, April 26, 2020, the question is asked: Why has Seattle largely escaped the ravages of COVID-19, while New York City has been ravaged?

   The short answer by Duhigg: A bit of luck (a flu test study whose swabs later revealed the widespread presence of COVID-19, and city leadership which listened closely to scientists (Seattle, by the way, is the world capital of epidemiologists).

   Here are the numbers. As of April 27, Seattle (King County) had 5,863 cases of COVID-19, and 408 deaths. As a % of Seattle’s population, 744,955,   that comes to: 0.8 % of the population contracted the virus, and 0.05% of the population died from it.

     For New York City, 160,000 cases have been identified, or over 2% of the population, 8.4 million; there have been 12,287 deaths, or 0.15% of the population.

   Basically, Seattle proportionally has had a third of the COVID-19 cases that New York City has. True – Seattle is less dense than NYC, and has fewer homeless and poor…

   But why? Why did Seattle largely escape? In short: Seattle did its lock down a week or 10 days before New York City did. And those few days were enough to save many many lives. But why did Seattle get this head start?

   Here is the story. Warning: It’s long, 2,300 words. The heroes? Seattle-based scientists – and a little-known King County executive named Dow Constantine. His wisdom and prompt action saved many many lives.   The story by Duhigg is rather long, but worth reading:

   “The first diagnosis of the coronavirus in the United States occurred in mid-January, in a Seattle suburb not far from the hospital where Dr. Francis Riedo, an infectious-disease specialist, works. When he heard the patient’s details—a thirty-five-year-old man had walked into an urgent-care clinic with a cough and a slight fever, and told doctors that he’d just returned from Wuhan, China—Riedo said to himself, “It’s begun.”

   “For more than a week, Riedo had been e-mailing with a group of colleagues who included Seattle’s top doctor for public health and Washington State’s senior health officer, as well as hundreds of epidemiologists from around the country; many of them, like Riedo, had trained at the Centers for Disease Control and Prevention, in Atlanta, in a program known as the Epidemic Intelligence Service. Alumni of the E.I.S. are considered America’s shock troops in combatting disease outbreaks. The program has more than three thousand graduates, and many now work in state and local governments across the country. “It’s kind of like a secret society, but for saving people,” Riedo told me. “If you have a question, or need to understand the local politics somewhere, or need a hand during an outbreak—if you reach out to the E.I.S. network, they’ll drop everything to help.”

   “Riedo is the medical director for infectious disease at EvergreenHealth, a hospital in Kirkland, just east of Seattle. Upon learning of the first domestic diagnosis, he told his staff—from emergency-room nurses to receptionists—that, from then on, everything they said was just as important as what they did. One of the E.I.S.’s core principles is that a pandemic is a communications emergency as much as a medical crisis. Members of the public entering the hospital, Riedo told his staff, must be asked if they had travelled out of the country; if someone had respiratory trouble, staff needed to collect as much information as possible about the patient’s recent interactions with other people, including where they had taken place. You never know, Riedo explained, which chance encounter will shape a catastrophe. There are so many terrifying possibilities in a pandemic; information brings relief.

     “A national shortage of diagnostic kits for the new coronavirus meant that only people who had recently visited China were eligible for testing. Even as EvergreenHealth’s beds began filling with cases of flulike symptoms—including a patient from Life Care, a nursing home two miles away—the hospital’s doctors were unable to test them for the new disease, because none of the sufferers had been to China or been in contact with anyone who had. For nearly a month, as the hospital’s patients complained of aches, fevers, and breathing problems—and exhibited symptoms associated with covid-19, such as “glassy” patches in X-rays of their lungs—none of them were evaluated for the disease. Riedo wanted to start warning people that evidence of an outbreak was growing, but he had only suspicions, not facts.

   “At the end of February, the C.D.C. began allowing the testing of patients with unexplained respiratory-tract infections or “fever and/or symptoms of acute respiratory illness.” Riedo called a friend—an E.I.S. alum at the local department of health. If he sent her swabs from two patients who had needed ventilators but had tested negative for influenza and other common respiratory diseases, would she test them for covid-19? At that point, there had been only sixteen detections of the coronavirus in the U.S., and only the one in Washington State. “I can’t remember why we picked those two patients,” Riedo told me. “I was sure they’d be negative. But we thought it would be good to start collecting data, and it was a way to make sure the testing lab was working.” The health official told him to send the samples to her lab.

   “Riedo remembered that other local researchers had been conducting a project called the Seattle Flu Study. For months, they had collected nasal swabs from volunteers, to better understand how influenza spread through the community. During the previous few weeks, the researchers, in quiet violation of C.D.C. guidance, had jury-rigged a coronavirus test in their lab and had started using it on their samples. They had just found a positive hit: a high-school student in a suburb twenty-eight miles from Seattle, with no recent history of foreign travel and no known interactions with anyone from China. The boy wasn’t seriously ill; if the researchers hadn’t done the test, the infection probably never would have been detected. The genetic sequence of the boy’s virus was unnervingly similar to that of the man with the first known case, even though the researchers couldn’t find any connections between them. The frightening implication was that the coronavirus was already so widespread that contagion was passing invisibly among community members.

   “On February 28th, around the time that Riedo learned of the covid-19 cluster at the Life Care nursing home, the news was also relayed to another E.I.S. alum, Dr. Jeff Duchin, the top public-health physician for Seattle and surrounding King County. To Duchin, the cluster suggested that there was already an area-wide outbreak. He told Dow Constantine, the King County Executive, that it was time to start considering restrictions on public gatherings and telling residents to stay home. This advice struck Constantine as possibly crazy. There were only two dozen covid-19 diagnoses in the entire nation. Life looked normal. How could people be persuaded to stop going to bars, much less to work, just because a handful of old people were sick?

“At that moment, there were no known U.S. coronavirus fatalities. Schools, restaurants, and workplaces were open. Stock markets were near all-time highs. But when Riedo stopped to calculate how many of his hospital employees had been exposed to the coronavirus he had to quit when his list surpassed two hundred people. “If we sent all of those workers home for two weeks, which is what the C.D.C. was recommending, we’d have to shut down the entire hospital,” he told me. He felt like a man who, having casually swatted at a buzzing insect, suddenly realized that he was beneath a beehive.”

   Constantine told me, “Jeff recognized what he was asking for was impractical. He said if we advised social distancing right away there would be zero acceptance. And so the question was: What can we say today so that people will be ready to hear what we need to say tomorrow?” In e-mails and phone calls, the men began playing a game: What was the most extreme advice they could give that people wouldn’t scoff at? Considering what would likely be happening four days from then, what would they regret not having said?

   “Even for public-health professionals, the trade-offs were painful to contemplate. At a meeting of public-health supervisors and E.I.S. officials in Seattle, an analyst became emotional when describing the likely consequences of shutting Seattle’s schools. Thousands of kids relied on schools for breakfast and lunch, or received medicine like insulin from school nurses. If schools closed, some of those students would likely go hungry; others might get sick, or even die. Everyone also knew that, if the city shut down, domestic-violence incidents would rise. And what about the medical providers who would have to stop working, because they had to stay home with young kids? “It was overwhelming,” one E.I.S. official told me. “Every single decision had a million ripples.”

   “Yet the burdens caused by closing the schools could make an enormous difference in curtailing the spread of the virus: all kinds of parents would have to stay home. In 2019, Seattle had closed schools for five days after a series of snowstorms. Afterward, the Seattle Flu Study discovered that traffic in some areas had nearly disappeared, public-transit use had tumbled, and the transmission of influenza had dropped.

   “Constantine thought that announcing school closings was a potent communication strategy for reaching even people who weren’t parents, because it forced the community to see the coronavirus crisis in a different light. “We’re accustomed to schools closing when something really serious happens,” Constantine told me. “It was a way to speed up people’s perceptions—to send a message they could understand.”

     “While the logistics of classroom closures were being worked out, Constantine contacted Brad Smith, the president of Microsoft—which is headquartered in Redmond, east of Seattle—and asked him to consider ordering employees to work from home. “Microsoft is a big deal here,” Constantine told me. “I thought if they told everyone to stay home it could shift how the state was thinking—make the pandemic real.” Microsoft, as a tech company, was poised to switch quickly to remote work, and could demonstrate to other businesses that the transition could occur smoothly. On March 4th, with only twelve known covid-19 fatalities across the nation and no diagnoses among Microsoft workers, the company told employees to stay home if they could. Smith told me, “King County has a strong reputation for excellent public-health experts, and the worst thing we could have done is substitute our judgment for the expertise of people who have devoted their lives to serving the public.” Amazon, which is also headquartered in the area, told many of its local employees to work from home as well. “That’s a hundred thousand people suddenly staying home,” one Seattle resident told me. “From commute traffic alone, you knew something big had happened.”

   “On February 29th, Constantine held a press conference. He had asked Riedo, Duchin, and Kathy Lofy—another E.I.S. alum and the state’s top health officer—to play prominent roles. Duchin spoke first, and it was as if he had prepared his remarks with the Field Epidemiology Manual in hand. “I want to just start by expressing our deep and sincere condolences to the family members and loved ones of the person who died,” he said. He explained what scientists knew and did not know about the coronavirus, and noted, “We’re in the beginning stages of our investigation, and new details and information will emerge over the next days and weeks.” He predicted that “telecommuting” was likely to become mandatory for many residents, and repeated several times an easy-to-remember sohco: “more hand washing, less face touching.” Duchin told me that his words had been chosen carefully: “You have to think about managing the public’s emotions, perceptions, trust. You have to bring them along the path with you.” Since then, Washington State politicians have largely ceded health communications to the scientists, making them unlikely celebrities. “Hey people!! Jeff Duchin is the real deal,” one fan tweeted. A newspaper hailed him as “a bespectacled, calming presence.”

   “Constantine told me that he understands why politicians “want to be front and center and take the credit.” And he noted that Seattle has many of “the same problems here you see in Congress, with the partisanship and toxicity.” But, he said, “everyone, Republicans and Democrats, came together behind one message and agreed to let the scientists take the lead.”

   “By the time Seattle’s schools were formally closed, on March 11th, students and teachers were already abandoning their classrooms. The messaging had worked: parents were voluntarily keeping their kids home. Cell-phone tracking data showed that, in the preceding week, the number of people going to work had dropped by a quarter. Within days, even before Washington’s governor, Jay Inslee, issued official work-from-home orders, almost half of Seattle’s workers were voluntarily staying away from their offices. When bars and restaurants were officially closed, on March 15th, many of them were already empty. Constantine himself had been working from home for a week. He was giving interviews all day, and always underscored to reporters that he was speaking from his bedroom, and that the noises in the background were coming from his children, who were home from school. After he heard that the county’s basketball courts were still being heavily used, he ordered them closed.”

     In Seattle, mainly the scientists spoke, not the politicians. And the politicians listened.

     Seattle should be carefully studied; our understanding has already been illuminated thanks to Duhigg’s fine reporting.  Well done, Duhigg.

     I urge everyone to read the full article in The New Yorker, online.

Understanding Vaccine Science: A Primer

By Shlomo Maital

Here is my effort to understand where we stand, with regard to a COVID-19 vaccine.

There are several different types of vaccines, each with its own strategy.

  1. Live attenuated vaccines. These use the virus itself, weaken it, and inject it; the body’s immune system is alerted and springs into action, developing antibodies that can defeat the virus if and when it invades the human body.   This is how vaccines against measles and mumps work. Measles vaccine has existed since 1950 and still is effective; measles has not mutated to defeat it.
  2. Inactivated vaccines. These use ‘dead’ viruses. Even though ‘dead’ the presence of the virus in the body activates the immune system.   Vaccines based on this approach are effective against hepatitis and polio. Polio vaccine has been effective since the early 1950’s.
  3. Subunit vaccines. These vaccines use specific pieces of the virus, key pieces, to activate immunity and neutralize the virus if and when it invades the human body. Examples: vaccines against whooping cough and shingles.
  4. Toxoid vaccines. These use toxins produced by the germs, to trigger the immunity of the body that attacks the harmful toxins. E.g. vaccines against diphtheria and tetatnus.
  5. DNA/ RNA vaccines. These are the newest types of vaccine.  

   At Emory University, in Atlanta Georgia, for example, a new type of mRNA vaccine against COVID-19 is now being tested in humans (an Emory medical student). Here is how it works: “messenger RNA” is the protein made by the virus, found on those spikes you see in cartoon illustrations, these spikes poke through the cell walls to invade the cell and use its DNA to reproduce. mRNA vaccines teach the body to produce, identify and attack those key proteins, neutralize them and hence prevent the virus from poking through cell walls.

     All over the world, desperate races are underway to develop a COVID-19 vaccine. All these different approaches are being used. Many labs are trying to use existing vaccines against related illnesses and adapt them.

   A major problem: There has not yet been a vaccine effective against coronavirus (e.g. the common cold, which is a variant of corona). And the DNA/RNA approach is relatively new and untried.

     With so many bright hard-working scientists at work day and night, there will be a breakthrough. And I believe it will come sooner rather than later. One of the key sparkplugs of creativity is desperation, and the world today is desperate for a vaccine. Add to that the profit motive – many billions of doses will be needed.

 

University Labs – to the Rescue! Paul Romer’s Plan

By Shlomo Maital

Nobel Laureate Paul Romer, NYU

   I am collecting material on “emergence strategies” – how nations will release citizens from lockdown and isolation, and my sense of doom is growing. In the 1918 influenza pandemic, the second wave killed far far more people than the first, after the first wave subsided and everyone went back to business as usual.

   Muddying the picture further are politicians, who pander to the ignorant and think doing so will get them re-elected. If they are, they will mount the victory podium by stepping on the bodies of hapless victims – a lot of them.

   This is why I believe we should all listen carefully to Nobel Laureate in Economics Paul Romer, NYU, and his plan. (See “Roadmap to Responsibly Reopen America” available at https://roadmap.paulromer.net). )  The bottom line: Employ university labs to produce COVID-19 tests, at scale — millions of them. It IS do-able!

    Romer writes, in the introduction to his Roadmap: “America is confronting two crises: an economic crisis laying waste to our livelihoods and a health crisis threatening our lives. The twin crises are deeply intertwined: our economy cannot be re-opened without credibly addressing fears of infection and resurgence.   The immediate reaction, a national lockdown, was successful in slowing the virus. We must now shift to a plan that balances the need to protect our health and reopen our economy by locking down only those who are infectious. This paper presents a simple, scalable, and credible solution: introduce a comprehensive “test and isolate” policy, making it safe for Americans to return to work and keeping the infection rate below 5% of the population. Until a vaccine is developed and deployed, the simplest and safest path to this outcome is a national testing strategy that marshals our existing resources to test everyone in the U.S. once every two weeks and isolates all those who test positive. It does not rely on any new technologies, is far less disruptive and costly than our current policy, and will work even in a worst-case scenario. Below is a roadmap to a future in which the American people are confident that their health and our economy’s future are protected against this virus.”

   Here are the main elements of his plan:   1. Expand the pool of testing capacity, mainly by establishing a network of university labs, which DO have the capacity to scale up and test effectively; 2. Find a revenue stream that can be used to find those who are spreading the disease; 3. Starting testing essential workers (e.g. healthcare), and expand to, e.g. grocery clerks; 4. Expand to those who need urgently to return to work. 5. Finally, offer tests to everyone…EVERYone!

    The plan calls for testing every person in the U.S., with essential workers taking priority. Anyone who tested positive would be isolated. Tests would be administered “regularly,” with every two weeks the recommendation. That would mean 25 million tests per day.

In order to get testing to those levels, Romer advocates for removing regulatory barriers and establishing a network of university and national labs.   It would also require substantial funding – about $100 billion altogether, including the costs of infrastructure and training.  Those funds would be issued in block grants to the states. $100 b. is a lot – but a drop in the bucket, compared to the trillions the US is spending now on emergency bailouts.

   Romer notes there are hidden costs in NOT testing widely. Under lockdown, Romer says,”the U.S. economy loses $500 billion per month. Lifting the lockdown without mass testing to ease that fear may only reduce losses by about $100 billion.”

   The US has many Nobel Laureates in Economics. Why not bring them to Washington, put their heads together, and work out a well-considered strategic long-range plan for emergence? Including Romer’s?   The economists now serving in the Trump administration are either Wall St. rapacious capitalists (Mnuchin) or low-level cranks (Kudlow). This does not bode well for the US.

In the Eye of the Corona Storm: A Drug That Works

By Shlomo Maital

   

Yaky Yanay

    My good friend Dr. G. N. Rao, founder of the L V Prasad Eye Institute in Hyderabad, India, drew my attention to this:   A coronavirus drug that works.

     According to Maayan Jaffe-Hoffman, writing in the Jerusalem Post:

   “Israeli-based Pluristem has treated its first American patient suffering from COVID-19 complications under the country’s compassionate use program.

 The news comes days after a report by the company showed that six critically ill coronavirus patients in Israel who are considered high-risk for mortality were treated with Pluristem’s placenta-based cell-therapy product and survived, according to preliminary data provided by the Haifa-based company.

Let me provide some background.

Researchers report: “When it comes to COVID-19, recent research has suggested about 20% of people get the severe form of the disease. Many in this group become critically ill because of their advanced age or underlying health conditions. But those who were previously healthy and are in their 30s, 40s, 50s are very likely experiencing a cytokine storm.”

A small but significant fraction of COVID-19 patients, mainly younger ones, die not from the ravages of the virus on their lungs, but because their body over-reacts, as their immune system kicks in violently and creates this “cytokine storm”. It turns out that an overly strong immune reaction is just as bad, or worse, than a weak reaction.

How does Pluristem’s drug work? Here is how CEO Yaky Yanay explains it:

“Patients who are in severe condition and dying are actually dying from a severe respiratory condition. What is actually happening is there is a very high level of inflammation and at a certain point the immune system of the patient will attack [the patient], mostly in the lungs.   Until now, Pluristem’s technology has been largely used to treat people suffering from poor blood flow to the legs, but the company’s scientists were able to quickly repurpose the cells to treat coronavirus patients.   “We take cells from the placenta after full-term delivery and we have developed technology to expand the cells to very large numbers, in an environment that mimics the human body,” Yanay said. “The technology allows us to treat more than 20,000 people from a single placenta.”

       His team “programs” the cells, which then have a wide range of proteins they can secrete. The cells don’t just deliver the proteins but also “adjust the level of secretion based on signals they receive from the body.”

       The US FDA allows using the drug on compassionate grounds for very seriously ill patients. But for widespread use, full-scale three-phase clinical trials are necessary, and are already well underway.

How Israel Is Handling the Nursing Home Crisis

By Shlomo Maital

In the novel coronavirus pandemic, nursing homes have been a disaster, with many tragedies. This is just one terrible example, in New Jersey:

           “29 Dead at One Nursing Home From the Virus. Or More. No One Will Say.] By Monday, the police in a small New Jersey town had gotten an anonymous tip about a body being stored in a shed outside one of the state’s largest nursing homes. When the police arrived, the corpse had been removed from the shed, but they discovered 17 bodies piled inside the nursing home in a small morgue intended to hold no more than four people.   “They were just overwhelmed by the amount of people who were expiring,” said Eric C. Danielson, the police chief in Andover, a small township in Sussex County, the state’s northernmost county.

  In Israel, too there have been nursing home tragedies. Family are banned from visits; and caregivers bring in the virus and the elderly are afflicted.

     After several such scandals, Israel has taken action. A former Director-General of the Ministry of Health, Dr. Ronnie Gamzu, now head of a large Israeli hospital, was asked by the Ministry of Health to shape a comprehensive plan for protecting Israel’s nursing home residents. His 100 page document is revealing.

     It calls for 600 Home Front soldiers to monitor entry to the homes. Notice that a former Health Ministry senior official does not trust the Ministry itself to handle the problem, but instead appeals to the Army. And those 600 can be increased to 1,000, if needed. Many in Israel believe that the overall management of the pandemic should have been placed in the hands of an interdisciplinary team led and run by the Israel Defense Forces.

     Nursing homes are vulnerable. The elderly in them need caregivers. And the caregivers need the work, because they are poorly paid. So, you cannot quarantine or exclude the caregivers, despite the risk. Testing every single one is a possible answer, but you would need to do this very often – Caregiver A could be ‘clean’ today, but infected tomorrow.

   Better late than never? Hard to say that, when it comes to the elderly, many of whom survived the Holocaust. Let us protect and care for them properly, and not make excuses.

    

Blog entries written by Prof. Shlomo Maital

Shlomo Maital
April 2020
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