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Sunday, May 31, 2020

Amazon, Apple, Walmart, Others Shut Stores, Cut Operations In Protest-Hit Areas

A number of companies in the United States have decided to shutter their retail outlets and scale back on business in cities most disrupted by the protests organized in the wake of George Floyd’s death.


Apple Inc. AAPL 0.1% said it was keeping a number of its stores in the country closed on Sunday in light of the protests, without specifying how many stores, CNBC reported. It didn’t say whether the closures would be extended beyond Sunday if the protests continued.
The company has only been operating about half of its 271 U.S. stores due to the novel coronavirus (COVID-19) pandemic.
The move follows the looting of a number of Apple retail outlets across the country, including in Minneapolis, Washington D.C., and Brooklyn.
Amazon Inc. AMZN 1.72% sent out a notice to its part-time delivery executives across a dozen cities, including Minneapolis, Chicago, and Los Angeles, working under the Flex program, to stop making deliveries “immediately” and return home, as reported by CNBC.
The company adjusted the Flex schedule, under which drivers can deliver Amazon products using their own vehicles as an independent contractor and get paid, to match curfew timings across cities, CNBC noted.
Amazon’s subsidiary supermarket chain Whole Foods also said it was temporarily closing or reducing operating hours at a number of outlets across the country.


Walmart Inc. WMT 0.21% had closed some of its stores in Minneapolis and Atlanta on Friday, after a few of them became a target of looting.
The retailer on Sunday said it was further closing several hundred stores across the country, according to CNBC.
Walmart said it would access the situation on an everyday basis, and some of the outlets could be reopened as soon as Monday if there’s no physical damage.


Target Corporation TGT 3.36%, in a statement late Saturday, said it was shuttering 175 stores and reducing hours at a few others until further notice.
Chief Executive Officer Brian Cornell said the company was working to ensure that workers displaced as a result of the protests, including more than 200 from its Minneapolis Lake Street store, are supported, including “receiving full pay and benefits in the coming weeks.”
Among other retailers, Nike Inc. NKE 0.07% said it has temporarily shut some of its stores, and Adidas AG ADDYY 1.66% closed all its outlets, the Wall Street Journal reported.

South Korea’s Celltrion: COVID-19 drug shows drop in viral load in animal testing

South Korea’s Celltrion Inc said on Monday its experimental treatment of COVID-19 demonstrated a 100-fold reduction in viral load of the disease in animal testing.
Drugmakers worldwide are rushing to develop treatments and vaccines for the illness that has caused more than 371,000 deaths globally.

The pre-clinical study of the drug showed improved recovery in runny nose, cough and body aches after the first day of treatment, and clearing of lung inflammation within six days, the company said in a statement.
Celltrion has research experience with other types of coronavirus conditions such as Middle East Respiratory Syndrome (MERS). It hopes to commence first in-human clinical trials for the COVID-19 treatment in July, said Kwon Ki-Sung, head of the firm’s research and development unit.

“(Celltrion) has the capability to roll out mass production of the therapeutic antibody treatment once it is ready,” Kwon said.

Plastic’s Back! Covid Contamination Concerns Crush California ‘Green’ New Deal

Disposable plates, silverware, and straws are making a comeback in California. New guidelines issued by the CDC recommend restaurants use plasticware by default as a way to limit the spread of the virus upon reopening.
Environmental groups have become infuriated with the new recommendation, as it now means all their hard work to ban plastic straws and push a “Green” New Deal could come to an abrupt end (maybe temporarily) because according to the CDC, throwaway dishes, utensils, napkins, and tablecloths could reduce virus spread.
California recycling and clean water groups recently delivered a letter to Gov. Gavin Newsom, questioning how exactly plasticware diminishes the probabilities of contracting the virus and also accused petrochemical companies of “trying to influence CDC guidelines for reopening food establishments in their favor.”
“The idea that the CDC recommends that single-use disposable items should be preferred seems a little illogical to me,” Chris Slafter, interim coordinator of Clean Water Action’s ReThink Disposable program, which provides grants to restaurants and advises them on how to transition and replace plasticware to more sustainable products, told Politico. “Someone still has to handle that item before it goes into a customer’s hand.”
In pre-corona times, California and its green activists led the way in eliminating plastic straws and other petroleum‐based plastics from the restaurant industry as they have long criticized the items eventually end up in the oceans, polluting and killing wildlife.
We recently noted that microplastics have also ended up in human stool.
Now, in post-corona times, with California’s restaurant industry crashed (according to OpenTable data from late May), eateries that have been opened with carryout only and ones that have just fully reopened, have turned to plasticware over the CDC’s new sanitary guidelines.
OpenTable restaurant data through the end of May
Restaurants in other states have also followed the new guidelines with the switch to disposable menus, plates, silverware, etc.
However, Stanford University epidemiologist Steven Goodman does not see a difference in plasticware from regular plating, in terms of reducing virus spread, as he notes, there’s still human staff behind the scenes making the food.
“It doesn’t sound like there should be a big difference if they’re handled carefully,” Goodman said. “Washing the plates well should get rid of [the virus], and so the only difference could be how they’re handled between the time when they are on the table and in the sink or in the washing machine.”
Sharokina Shams, the California Restaurant Association’s vice president of public affairs, told Politico in an email response that “many of the current local public health orders (which are a response to the coronavirus pandemic) do put an emphasis on single-use products, and cities have been moving to suspend the ban on plastic bags.”
“It’s also interesting to note that the number of delivery and takeout orders went up during stay-at-home/shelter-in-place orders. If that becomes a long-term pattern, you may see the demand for single-use products rise,” said Shams. 
And just like that, who would’ve ever thought California’s green movement would get derailed by a virus.

NY state suspends liquor licenses over social distancing infractions

The state has suspended the liquor licenses of 18 establishments since late March because of social-distancing violations — including one in Queens that allegedly claims local racists are behind the move.
The Hangar 11 Bar & Grill in Kew Gardens landed in hot water after a flood of 311 calls complaining of such things as crowds milling around inside and out.
The State Liquor Authority says on its Web site that the Metropolitan Avenue bar had patrons buy a bag of chips just so the establishment could say it was selling them “food’’ to go along with their booze as required by law — and enough of a crowd was created that a flood of local residents called authorities to complain.
But a tweet apparently posted by the bar Friday, the day its license was temporarily suspended, said, “Due to the efforts of a tiny percentage of racist neighbors in our beautiful Kew Gardens neighborhood, we will be shut down for a few days.’’
The alleged tweet included the hash tags #staysafe, #icantbreathe and #racism sucks. It has since been taken down, but not before someone took a screenshot and sent it to The Post.
The bar tweeted the next day, “NYC is a melting pot. We have always welcomed everyone. Most of our 23,000 community members too. Just a handful of hateful and bored members flooding 311 with calls yet we’ve had zero fights.’’
The neighborhood around the bar is predominantly white, while the business attracts customers of all races.
There were 80 complaints lodged against the bar over social-distancing rules between March 20 and May 9, the liquor authority said. It is still closed and will face a hearing before the SLA over its license.
“The people who filed legitimate complaints received justice,” wrote a member of a Kew Gardens Facebook page.
Another resident was incensed over the bar’s tweets.
“The fact that they played the race card is so outrageous,’’ the person wrote on the closed page. “All I can say, this establishment seems to not understand the community they serve.’’
The bar did not respond to a request for comment from The Post.
Hangar was one of seven New York City establishments to have its liquor license temporarily suspended because of social-distancing issues amid the coronavirus pandemic.
Another Hangar, on Steinway Street in Astoria, Queens, also had its license yanked.
Other bars whose licenses were temporarily suspended included the Atlantic Boat Club in Brooklyn, Sam Ceccilio in Queens and St. Bee’s bar in The Bronx.

To keep the streets safe, New York City needs its crowds back

Anarchists are throwing bombs at cops, officers are driving into crowds and looters are smashing stores. That’s the good news. New York could survive a one-off riot. But the city has lost equilibrium — and has no leader.
It’s a fundamental test of Gotham’s ability to govern itself.
The only proper political response to street protests in a pandemic is: “Don’t protest.” Stay home. Corey Johnson, Scott Stringer, Eric Adams should go out together, unguarded, to say: “Go home, now. We will do one-on-one video calls with you. It does no good to George Floyd’s memory for more people to die of COVID.” Problem is, constructive advocates for change are staying home, without being told. Crowds, thus, are self-selected people, who are, by definition, heedless of personal safety.
So there aren’t enough responsible protesters to balance anarchists and looters. On a normal Saturday night, violent “protesters” wouldn’t get far — it would be hard to smash windows amid throngs of restaurant-goers and club kids, out for a good time.
Put aside sensationalist scenes, and this has been the city’s dilemma for months. Looting? We’ve had slow-motion looting since the lockdown started.
For the 28 days ’til Memorial Day, burglary, including theft of defenseless pets, soared 35 percent; auto theft rose by 63 percent.
These aren’t crimes of poverty, sending a message. They are crimes of opportunity. There are no — rational — eyes on the street.
Pointless violence? Murder is up — to 24 from 19 over the month until Memorial Day, plus four stabbing deaths in one day last week.
It isn’t that New York has suddenly become more violent. It’s urban disequilibrium. Mamadou Diallo, an essential Uber Eats worker, was shot and killed waiting for a bus — because subways were closed.
Empty streets provide opportunity for retaliation. Over the month, shooting victims have doubled, to 97 from 47. In mid-May, 16-year-old Tyquan Howard died on a Crown Heights sidewalk, his murder likely revenge for group-beating a teen girl.
It is really hard, perhaps impossible, to police your way out of lost equilibrium, though bail “reform” that looses violent suspects on streets hardly helps.
So Mayor Bill de Blasio’s riot strategy is wrong: He thinks the NYPD can get us out of this. It can’t. Policing is one tool to keep balance in a well-balanced city.
The NYPD is deploying the crowd-control tactics that it would for a parade. This is not that. These are anarchists who want to provoke police into bad action. The police are their props.
Police SUVs and guns are useless — and liabilities — unless police are going to drive or shoot into crowds. Let’s pray they will not, because de Blasio, in throwing crowds of police to face off with crowds of literal bomb-throwers for days on end, is counting on prayer.
All it takes is one loud noise.
A healthy community mostly polices itself. It has trusted leaders — elected, business, community — who can speak credibly to different groups, including unsavory ones.
It has elected officials who aren’t afraid to say: “It is wrong to throw IEDs at police officers, and doing so makes the police vulnerable to fear, anger and panicked actions.” But we don’t even have leaders who say that burgling pandemic-shuttered stores is unacceptable — and will be met with stronger charges for aggravating circumstances.
Paying criminals the compliment of demanding they act with self-restraint in a crisis would anger some anonymous scold on Twitter — so the political, business and community-organizer classes stay quiet.
We face months of this — and risk driving away our tax base, scared to come back and reopen in a city re-shuttered by wildcat unrest. That will solve poverty.
What we need, oddly, is a John Lindsay. Lindsay was flawed. But he didn’t hide behind his police. He went out — alone — in 1968 to face angry crowds and prevent rioting that killed other cities. De Blasio is no John Lindsay.
Who is?
Nicole Gelinas is a Manhattan Institute senior fellow.

Retailers, Restaurants Hit in Floyd Protests, Add to Coronavirus Damage

Many retailers and restaurants, already crippled by the coronavirus pandemic, are grappling with damage to their properties and new closures following protests sparked by the death of George Floyd that have sometimes turned violent.
From Minneapolis, where Mr. Floyd died while handcuffed and in police custody, to California and Georgia, big and small retailers and restaurants have shut locations in anticipation of violence or are working to rebuild after destruction over the past week.
Target Corp., Walmart Inc., Nike Inc. and small family businesses have collectively closed hundreds of locations or are recovering from looting and physical damage related to protests. Adidas said it was temporarily closing all its U.S. stores.
Many executives and business owners expressed solidarity with protesters, who object to broader issues of racism and social justice.
Around a dozen Walmart stores have been damaged, with more closed pre-emptively. That has included looting and other property damage, but no employees have been hurt, a Walmart spokesman said Sunday.
“What’s disturbing over the last 24 hours is it isn’t just at night,” the spokesman said. “We’ve even had issues this morning in broad daylight. We want to make sure our associates are safe.”
Walmart Chief Executive Doug McMillon said in a statement Friday that “this week is further proof we must remain vigilant in standing together against racism and discrimination.”
Target Corp., which is based in Minneapolis, over the weekend closed more than 200 U.S. stores, boarding up many of them pre-emptively, said a spokesman. The situation is fast-moving and some stores have reopened, in some cases with more limited hours, the spokesman said.
Last week, a Target store in south Minneapolis on Lake Street was one of the first U.S. businesses to be looted and badly damaged. Around seven Target stores have been damaged around the country, according to the company’s website.
“Most of those stores have damage where we anticipate we can open in the coming weeks, with the exception of the Lake Street store,” which Target aims to open by the end of the year, said the spokesman. Store workers will be paid for up to 14 days during store closures and can work at other locations, the company said.
“We are a community in pain,” Target Chief Executive Brian Cornell said in a statement Friday. “The murder of George Floyd has unleashed the pent-up pain of years,” he said.
Walmart and Target stores were open during the coronavirus pandemic that forced thousands of retailers and restaurants to shut in March and April, leading to millions of job losses.
Some of those businesses were just starting to reopen this month as protests kicked off following Mr. Floyd’s death during an arrest. Authorities have charged one of the arresting Minneapolis officers, Derek Chauvin, with third-degree murder and manslaughter. Mr. Chauvin was seen on video pressing his knee on Mr. Floyd’s neck while Mr. Floyd begged for help.
In some cities, smaller businesses bore the brunt of the damage. In Minneapolis, a family-owned liquor store, an Indian restaurant, a chiropractor and other businesses were left in rubble near the closed Lake Street Target.
Cynthia Gerdes, co-founder of Hell’s Kitchen in downtown Minneapolis, shut down her 18-year-old restaurant due to the coronavirus in March. She had drawn up plans to start offering takeout in July, but is now weighing how Mr. Floyd’s death and the resulting unrest will impact the city’s business and reputation going forward.
“It’s a double whammy. It’s a gut punch,” said Ms. Gerdes, whose business depends on conventions and office workers downtown.
Ms. Gerdes said her building near one of the city’s main police stations is now boarded up, with some windows smashed. She put up a sign in her restaurant’s windows supporting the protesters, but wonders about how long the impact will last.
“It’s just so surreal at this point,” said Ms. Gerdes, who said she was exploring options for her establishment and 138 employees.
Bob Grewal, a Subway franchisee and development agent for the sandwich company in the Los Angeles and Washington, D.C., areas, said one of the chain’s stores in downtown Washington was looted and had its windows smashed Saturday night. The store had just begun to reopen with limited hours after being closed for the coronavirus.
“They were just starting back up. It’s just horrible,” he said.
Police arrested looters that had targeted another Subway location in the hard-hit Fairfax District in Los Angeles on Saturday night, Mr. Grewal said. That store had just invested in food to get running again. Owners are contacting insurance companies and assessing the damage now, he said.
“It’s crazy. I was hoping to start opening back up. And then this happens,” he said.
“These business owners have nothing to do with this,” Mr. Grewal said. “They are suffering. The communities are suffering.”
A Starbucks Corp. spokeswoman said that it closed some of its stores Saturday for the safety of its workers after people damaged a handful of locations.
McDonald’s Corp. said Sunday that the burger company and its franchisees closed a small number of restaurants temporarily and are beginning to reopen them where safe.
“We are working closely with our franchisees to understand the impact,” the company said.
Joe Erlinger, the president of the U.S. division, said that he was personally shaken by the unrest and planned to hold discussions across the company about how to allow for diversity and inclusion.
“Quite simply, I am appalled by recent events in Louisville, Georgia, New York and Minneapolis,” Mr. Erlinger said in a letter over the weekend. “I feel shaken and I know many of you do, too. I share your concerns, sadness, and anger.
Some Nike and Adidas stores in major U.S. cities were looted and damaged in the protests. A Nike spokesman said employees weren’t harmed. The company, which previously made NFL quarterback-turned-activist Colin Kaepernick the face of an advertising campaign, launched a “Don’t Do It” ad, offering a spin on its popular catchphrase.
“For once, Don’t Do It…Don’t pretend there’s not a problem in America, ” the company said in a film shared on Twitter on Friday.
Adidas retweeted its competitor’s ad, along with the message: “Together is how we move forward. Together is how we make a change.”

Futures down more than 1% after rough weekend

Following a weekend of escalating violence across U.S. cities that’s knocked the coronavirus off the front page, S&P 500 futures are lower by 1.25% in Sunday evening action.

BioMarin gene therapy shows sustained benefit in hemophilia A study

BioMarin Pharmaceutical (NASDAQ:BMRN) announces updated data from an open-label Phase 1/2 clinical trial evaluating a single administration of gene therapy valoctocogene roxaparvovec in adults with severe hemophilia A. The results will be virtually presented at the World Federation of Hemophilia Summit June 14-19.
The mean annualized bleed rate (ABR) at year 4 in the 6e13 vg/kg cohort was 1.3. Six of seven participants experienced no spontaneous bleeds over the past year.
Mean ABR at year 3 in the 4e13 vg/kg cohort was 0.5. Five of six participants experienced no spontaneous bleeds over the past year.
Factor VIII activity levels remain in a range for efficacy in stopping/preventing bleeding.
No new safety signals have been reported and no patient has developed inhibitors to Factor VIII, experienced blood clotting events or withdrawn from the study.
The company’s U.S. marketing application is currently under FDA review with an action date of August 21 under Breakthrough Therapy and Orphan Drug status. Its application in Europe is under EMA review under accelerated assessment and Orphan Drug status.

65% of small Israeli start-ups could succumb to COVID-19: survey

Around 65 percent of small Israeli start-ups expect to cease operations in the next six months due to the economic impact of the coronavirus crisis, a poll released Sunday said.
The survey, conducted by the Israeli Innovation Authority (IIA)—a state agency that finances —and a consortium of tech industries, paints a gloomy picture of future in the self-styled “start-up nation”.
“The results of the survey show that many early-stage technology companies are facing bankruptcy, and the industry is not receiving sufficient assistance from the Israeli government,” said Karin Mayer Rubinstein, CEO and President of Israel Advanced Technology Industries (IATI).
The high-tech sector accounts for 10 percent of jobs in Israel.
The country’s economy was in full swing with unemployment at 3.4 percent in February, before the coronavirus pandemic struck a devastating blow to the global economy.
Joblessness has since surged to a peak of 27 percent, a trend that has not spared Israel’s technology sector.
According to the survey of the heads of 414 high-tech healthcare, software, hardware and communications companies, more than a third have put staff on leave of absence during the pandemic.
Israel has recorded more than 17,000 COVID-19 infections and more than 280 deaths out of a population of nine million.
Despite an initial easing of measures put in place to contain the contagion, the morale of some start-ups remains low.
Some 65 percent of high-tech companies with one to 10 employees believe they do not have sufficient resources “to continue beyond six months”, according to IIA chief Aharon Aharon.
Rubenstein said that an already approved emergency package of 1.2 billion shekels ($346 million) for the sector “is not sufficient”.
Without new public investment, “we are gravely concerned for a potential collapse of the high-tech industry as we know it, which would lead to an undermining of the entire economy”, she added.

Cancer cells greedy for glucose

To fuel their rapid proliferation, tumor cells rely on glycolysis, a primordial metabolic pathway that is easily exploited by cancers to gain energy to grow—and spread.
Glycolysis is the oldest form of energy production in living cells. It has been around for billions of years, having emerged before oxygen accumulated on Earth, and was the type of energy production for the planet’s first primitive forms of life.
The process involves the breakdown of glucose to yield energy for cellular metabolic activities. Bacteria use glycolysis, as do more complex organisms such as plants and animals. The latter, however, have developed more sophisticated forms of energy production, despite still having glycolysis with its lower energy yield. For example, the electron transport chain produces substantially more ATP—energy molecules—than does glycolysis. Still, many types of tumor cells use glycolysis preferentially to provide sufficient energy for growth and proliferation.
High rates of glycolysis in cells remain a well-established characteristic of many human tumors, report Drs. Jeremy Blaydes and Charles N. Birts of the Cancer Sciences Unit, Faculty of Medicine, at Southampton University in England. The energy-producing process provides cancer cells with metabolites that can be used as precursors for anabolic pathways.
Writing in the journal Science Signaling, Blaydes and Birts, along with a team of cancer researchers, found that in an in vitro breast cancer model, they were able to identify something startling new—they call it a glycolytic stress response, involving p53. The p53 gene carries the DNA blueprint for a protein called tumor protein p53. The protein plays a critical role policing cellular activities, such as and cell death. Mutations in p53, studies have long shown, allow cancer cells to grow and spread.
“Constitutive aerobic glycolysis—the Warburg effect—is a hallmark of cancer cells that is commonly caused by mutations in oncogenes and tumor-suppressor genes,” Blaydes and Birst wrote in Science Signaling.
“It has multiple consequences for tumor cells, including the ability to generate adenosine 5′-triphosphate (ATP), which decreases reliance on oxygen for ATP generation, thus reducing the generation of potentially damaging reactive oxygen species (ROS) by the mitochondrial electron transport chain,” the cancer researchers concluded.
In the 1920s, Otto Warburg demonstrated that cultured cancer cells have high rates of glucose uptake and secretion of lactate, even without a need for oxygen. Those three properties—glucose uptake, lactate secretion and creating energy without oxygen, are hallmarks of the Warburg effect.
Warburg was a German scientist in the early 20th century who first studied sea urchin eggs, but turned his attention to rat tumors in 1923. That switch had a lasting impact on the discipline of cancer biology, particularly in the understanding of energy production and use in . Warburg noticed that cancer cells fueled their own growth by sucking in huge amounts of glucose from the host’s blood. Today, positron emission scans can help identify cancers by pinpointing areas of the body where enormous amounts of glucose are being consumed by cells. Those cells are easily identified as cancerous because of their unmitigated greed for glucose.
Moreover, cancer cells invariably choose the ancient metabolic pathway—glycolysis—to produce energy. Cancer cells, Warburg realized, had figured out a way to ensure their survival by exploiting the oldest form of energy production on the planet. The Warburg effect is estimated to occur in 80 percent of cancers.
Now, the University of Southampton team is shedding new light on the energy production in cancer by zeroing in on p53. The protein, the researchers found, is regulated by “aerobic glycolysis” in . This is further mediated by the CtBP family of NADH-dependent transcriptional regulators, something Warburg never would have expected. “Through the provision of glucose-6 phosphate for the oxidative pentose phosphate pathway, glycolysis also facilitates the generation of a reduced form of nicotinamide adenine dinucleotide phosphate, which provides reducing equivalents for -protective pathways,” the team wrote.

Explore further
PGK1 protein promotes brain tumor formation and cancer metabolism

More information: Charles N. Birts et al. p53 is regulated by aerobic glycolysis in cancer cells by the CtBP family of NADH-dependent transcriptional regulators, Science Signaling (2020). DOI: 10.1126/scisignal.aau9529

COVID-19 Effect: Prescription Fills Mostly Down for Leading Drugs

Prescription fills for hydroxychloroquine/chloroquine spiked right after COVID-19 was declared a national emergency in March, but use of the drugs still remains well above 2019 levels, based on data from more than 58,000 U.S. pharmacies.
Hydroxychloroquine/chloroquine are also doing better than any of the prescription drugs in the top 10 based on total claims in 2019, Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital, Boston, and associates reported May 28 in a research letter in JAMA.
Prescription fills for hydroxychloroquine/chloroquine have been above 2019 levels every week since the national emergency was declared on March 13, with the high occurring during the week of March 15-21, when fills were 214% higher than the corresponding week in 2019. The lowest level in that time came during the week of April 12-18, with growth of 14.6% over 2019, the investigators said.
The drugs occupying the top 10 — amlodipine, amoxicillin, atorvastatin, gabapentin, hydrocodone-acetaminophen, levothyroxine, lisinopril, losartan, omeprazole, and sertraline — have not done as well. Losartan, the only one that hasn’t lost ground in any week since March 13, rose by almost 49% during March 15-21, but was down to a 1.7% rise by the end of the study period, they reported.
Meanwhile, the other drug touted as a treatment for COVID-19, azithromycin, has fallen farther than most of the top 10. By April 19-25, the last week of the study period, fills for the antibiotic were down 62.7%, compared with last year, the analysis showed. Only amoxicillin had dropped more (64.4%).
The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling, Dr. Vaduganathan and associates wrote.
The investigators used all-payer U.S. pharmacy data from 58,332 chain, independent, and mail-order pharmacies across 14,421 zip codes in 50 states, reflecting approximately 17 million deidentified claims, to estimate national prescription fills, they explained.

New coronavirus losing potency, top Italian doctor says

The new coronavirus is losing its potency and has become much less lethal, a senior Italian doctor said on Sunday.
“In reality, the virus clinically no longer exists in Italy,” said Alberto Zangrillo, the head of the San Raffaele Hospital in Milan in the northern region of Lombardy, which has borne the brunt of Italy’s coronavirus contagion.
“The swabs that were performed over the last 10 days showed a viral load in quantitative terms that was absolutely infinitesimal compared to the ones carried out a month or two months ago,” he told RAI television.
Italy has the third highest death toll in the world from COVID-19, with 33,415 people dying since the outbreak came to light on Feb. 21. It has the sixth highest global tally of cases at 233,019.
However new infections and fatalities have fallen steadily in May and the country is unwinding some of the most rigid lockdown restrictions introduced anywhere on the continent.

Zangrillo said some experts were too alarmist about the prospect of a second wave of infections and politicians needed to take into account the new reality.
“We’ve got to get back to being a normal country,” he said. “Someone has to take responsibility for terrorizing the country.”
The government urged caution, saying it was far too soon to claim victory.
“Pending scientific evidence to support the thesis that the virus has disappeared … I would invite those who say they are sure of it not to confuse Italians,” Sandra Zampa, an undersecretary at the health ministry, said in a statement.
“We should instead invite Italians to maintain the maximum caution, maintain physical distancing, avoid large groups, to frequently wash their hands and to wear masks.”

A second doctor from northern Italy told the national ANSA news agency that he was also seeing the coronavirus weaken.
“The strength the virus had two months ago is not the same strength it has today,” said Matteo Bassetti, head of the infectious diseases clinic at the San Martino hospital in the city of Genoa.
“It is clear that today the COVID-19 disease is different.”

Retailers already hit by coronavirus board up as U.S. protests rage

Retail giant Target Corp said on Sunday it shuttered stores across the United States as retailers already reeling from closures because of the coronavirus pandemic shut outlets amid protests that included looting in many U.S. cities.
Protests turned violent in places including New York and Chicago following the death in Minneapolis of a black man, George Floyd, seen on video gasping for breath as a white police officer knelt on his neck.
In Los Angeles, protests led to the looting of the Alexander McQueen clothing store on Rodeo Drive, and a Gucci store on the vaunted strip was marked with the graffiti slogan: “Eat the rich,” according to local media reports.

In the nearby Grove Shopping Center, which houses 51 upscale stores, Nordstrom, Ray Ban and Apple were broken into. Nordstrom Inc temporarily closed all its stores on Sunday, it told Reuters in an emailed statement.
“We hope to reopen our doors as soon as possible,” the statement said. “We had impacts at some of them and are in the process of assessing any damage so we can resume serving customers.”
The violence was widespread, and Target said it was closing or limiting hours at more than 200 stores. It did not specify how long the closures would last.

The company told Reuters it was beginning to board up its Lake Street store in Minneapolis, near where Floyd was killed, for safety and to begin recovery efforts. The company said in a statement that it would plan to reopen the store late this year.
“There is certainly potential for the resulting social unrest to hurt certain businesses like retailers and restaurants, and for it to further dent consumer and business sentiment,” said Robert Phipps, director at Per Stirling. “It is even possible, particularly if the unrest continues and spreads, that it would, all other things being equal, have a significant impact on investor psychology and the markets.”
U.S. retail sales have posted record declines as the novel coronavirus pandemic kept Americans at home, putting the economy on track for its biggest contraction in the second quarter since the Great Depression in the 1930s.

U.S. sends Brazil 2 million doses of hydroxychloroquine

The United States has supplied Brazil with 2 million doses of hydroxychloroquine for use against the coronavirus, the two governments said on Sunday, despite medical warnings about risks associated with the anti-malaria drug.
The White House released a joint announcement on the drug, whose use has been touted both by U.S. President Donald Trump and Brazilian President Jair Bolsonaro, just days after the World Health Organization suspended testing it in COVID-19 patients because of safety concerns.
Trump himself said in mid-May that he was on a regimen of hydroxychloroquine as a preventive measure, even though the U.S. Food and Drug Administration had issued a warning about its use for the coronavirus.

Bolsonaro, a right-wing leader who has forged personal ties with Trump, said recently he kept a box of the drug in case his 93-year-old mother needed it.
“The American and Brazilian people stand in solidarity in the fight against the coronavirus,” the statement said. “We are announcing the United States Government has delivered two million doses of hydroxychloroquine (HCQ) to the people of Brazil.”
“HCQ will be used as a prophylactic to help defend Brazil’s nurses, doctors and healthcare professionals against the virus. It will also be used as a therapeutic to treat Brazilians who become infected,” it said.

The two countries will also conduct a joint research effort that will include “randomized controlled clinical trials,” the statement said, adding that the United States would soon send 1,000 ventilators to Brazil.
Brazil reported a record 33,274 new cases of the novel coronavirus on Saturday, its Health Ministry said, and the death toll surpassed that of France and now ranks only below the United States, Britain and Italy.
Demand for the decades-old hydroxychloroquine has surged as Trump repeatedly promoted its use against the coronavirus despite a lack of scientific evidence.

Texas issues disaster declaration over George Floyd protests

Texas Gov. Greg Abbott issued a disaster declaration for the entire state Sunday in response to violent protests over the death of George Floyd.
The governor’s announcement came after violent clashes between police and demonstrators on Saturday in some of the Lone Star State’s largest cities, including Austin, Dallas, Houston and San Antonio, the Texas Tribune reported.
“Every Texan and every American has the right to protest and I encourage all Texans to exercise their First Amendment rights,” Abbott said in a statement. “However, violence against others and the destruction of property is unacceptable and counterproductive.”
The declaration, which allows the governor to designate federal law enforcement officials as Texas peace officers, comes one day after Abbott activated the Texas National Guard to help quell the protests.
The Texas Department of Public Safety has also dispatched more than 1,500 officers to help besieged local police departments deal with the demonstrations, the Tribune said.
More than a dozen cities throughout the US have been besieged by massive protests in response to the Memorial Day police custody death of George Floyd in Minneapolis.
Floyd, 46, was suspected of passing a counterfeit $20 bill when police pinned him to the ground for nearly four minutes despite his pleas that he couldn’t breathe.
Demonstrators from Los Angeles to New York, Chicago to Miami have seen widespread looting, vandalism and arson fires.

ASCO 2020: Looking Back on COVID-19 in Order to Move Forward

At the virtual ASCO 2020 annual meeting, Giuseppe Curigliano, MD, PhD summarized and reviewed the previous two presentations in this session, on the TERAVOLT and COVID-19 Cancer Consortium (CCC-19) initiatives.
The CCC19 study included 928 patients with various types of cancers. In contrast, the TERAVOLT study included 400 patients with thoracic malignancies only. Another important difference was that in the CCC19, all patients had confirmed Real-time PCR COVID-19 infection, while in the TERAVOLT study, patients had either confirmed COVID-19 infection or had clinically suspected or radiologically suspected infection.
Dr. Curigliano also assessed the mortality rate in the CCC19 study. With a median of 21 days of follow up, 121 patients — representing 13% of the entire cohort — had died. In the TERAVOLT study, the median follow-up was 33 days, and 35.5% had died. There are many hypotheses for why patients with thoracic malignancies have a higher death rate, but one of these hypothesis states that these patients are prone to develop microvascular obstruction of lung vessels with the formation of microclots, manifesting as the thrombo-inflammatory syndrome (Figure 1).
Figure 1 – Thrombo-inflammatory syndrome:

Table 1 compares the morbidity and mortality in the TERAVOLT and CCC19 studies and demontrates a higher mortality and hospitalization rate in the TERAVOLT study, but a lower ICU admission rate, and rate of mechanical ventilation. Table 2 demonstrates the independent factors for mortality in both studies, showing very similar risk factors. Table 3 shows important data as it presents the main differences between the two studies, including smoking status, gender, previous steroid use, cancer stage, and the region of patient residence. The data shown in Table 4 attempts to explain some of the presented differenced between these studies, which include the different accrual timeframe, the type of national and local government response to the COVID-19 pandemic, and the rate of critical care bed per capita, which was different in a staggering manner.
Table 1 – Morbidity and mortality in the TERAVOLT and CCC19 studies:
Table 2 – independent factors for mortality in the TERAVOLT and CCC19 studies:
Table 3 – CCC19 and TERAVOLT main differences:
Table 4 – CCC19 and TERAVOLT possible explanations for the major differences between the studies:
Dr. Curigliano moved on to discuss the mortality rates of COIVD-19 in cancer patients in areas that were hit with COVID-19 quite substantially. The mortality rate of patients with cancer and COVID-19 in New York City was markedly increased compared to non-cancer patients, and compared to all New York City COVID-19 patients. The mortality rate in cancer patients with COVID-19 was significantly higher when compared to all patients with COVID-19 in New York City (25% vs. 14%). Specifically, there was a 50% mortality rate among lung cancer patients, 40% mortality rate for breast cancer patients, 50% mortality rate for genitourinary cancer patients, and 38% mortality rate for gastrointestinal cancer patients.
When assessing the case fatality rate in cancer patients in Milan, Italy, cancer patients demonstrated markedly increased COVID-19 mortality rate compared to non-cancer patients admitted to the ICU. The case fatality rates in cancer patients with COVID-19 was 19% in elderly patients )>75 years old), while the overall mortality rate in cancer patients was 8%.
Dr. Curigliano moved on to discuss the major limitations of both the TERAVOLT and CCC19 studies. These included:
  • COVID-19 case definition in the TERAVOLT trial that was not standardized.
  • In the European centers the pandemic scenario resulted in very difficult triage decisions (TERAVOLT study).
  • The patient selection in the TERAVOLT study was problematic as well.
  • There was a high proportion of stage four non-small cell lung carcinoma in the TERAVOLT study.
  • In contrast, there was a high proportion of patients in remission in the CCC19 study.
  • There was no data presented on the occurrence of deep vein thrombosis or pulmonary embolism in both studies
  • There was no clear definition for eligibility to ICU.
  • Both studies were cross-sectional studies with no real-time data capture, no auditing, and no standardized outcome definitions.
  • In both studies, there are multiple biases, including selection bias, recall bias, confounding by indication, and changes in practice and or disease evolution.
  • Lastly, there was no propensity score adjustment, no control with non-cancer patients, and there was no stratification for the stage and lines of previous therapies.
  • In both studies, serious confounding may remain due to the impact of unmeasured confounders and unmeasured risks on treatment decisions.
The strengths of the studies include the fact that that these studies represent a real-world data set which investigates the risks for hospitalization and death in cancer patients. Importantly, these studies represent an unprecedented global effort to collect data of patients with cancer affected by COVID-19. Lastly, in both studies, similar independent factors were associated with increased mortality after adjustment, which included older age, increased number of comorbidities, worse performance status, active cancer, and chemotherapy alone or in combination with other treatments.
There are still many questions that remain regarding cancer care prioritization and care intensity optimization. It is not clear if cancer patients should be prioritized for the ICU triage for admission based on the disease stage. It is also unclear whether immunotherapy provides any kind of protective effect from COVID-19 infection and outcome.
In conclusion, older age, increased number of comorbidities, worse performance status, active cancer, and chemotherapy alone or in combination with other treatments, have been shown to increase the risk of mortality in cancer patients with COVID-19. It is important for centers to prepare for the treatment not only of suspected and confirmed cases of COVID-19, but also to consider the treatment of cancer patients with COVID-19 and prepare accordingly. Lastly, cancer treatment prioritization should balance interventions based on the magnitude of benefit in the clinical setting.
Before ending his talk, Dr. Curigliano discussed some research priorities in cancer patients. According to him, it is important to understand the utility of PCR testing in these patients. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to COVID-19. It is critical that we develop an epidemiological model to estimate the cumulative incidence of COVID-19 within a specific timeframe and pandemic scenario. We need to identify viral, environmental, and immunological factors that, in combination, will determine the dynamics of COVID-19. It is also critical to determine the morbidity and mortality associated with COVID-19 according to the specific treatment that is given to cancer patients (chemotherapy, targeted therapy, and immune checkpoint blockade).
To conclude his talk, Dr. Curigliano reiterated three important principles that continue to guide us through this pandemic:
  1. Transparency is the best policy.
  2. During this pandemic, there was an unprecedented collaboration among clinicians and scientists globally to work together and generate data for patients with cancer.
  3. Surprisingly, 21st-century science played a relatively small role in dealing and controlling the COVID-19 pandemic, while 19th-century methodology continued to prove it’s value, with early implementation of social distancing, personal protective equipment, and handwashing.
Presented by: Giuseppe Curigliano, MD, PhD, Associate Professor of Medical Oncology at the University of Milano, Head of the Division of Early Drug Development at European Institute of Oncology, Italy

ASCO 2020 virtual annual meeting – day 3

Our live coverage from this year’s slimmed down, virtual version of the American Society of Clinical Oncology (ASCO) annual meeting continues at 8am (ET) as we move into the third and final day of the oncology event.
It follows our live coverage of ASCO 2020 day 1 and day 2, during which we’ve already featured Amgen’s Kyprolis, AstraZeneca’s Tagrisso, rare cancers and genomics, BCMA therapy, COVID-19’s impact on cancer patients and much more.

View all the live coverage of the virtual ASCO 2020, and day three live blog is below (please allow the blog a few moments to load):
Last Updated: 38 minutes ago
38 minutes ago
J&J highlights data from lung cancer bispecific antibody
Johnson & Johnson’s Janssen unit also has some interesting data from a bispecific antibody aimed at lung cancers with a mutation that renders approved targeted drugs useless.
Amivantamab was created in collaboration with its development partner Genmab and the latest data from Janssen came from a small study in non-small cell lung cancer with EGFR exon20 insertion mutations.
Data came from the study of 50 patients, of whom 39 were evaluable at data cut-off in October.
This showed an overall response rate of 36%, and 41% in patients who had already received platinum-based chemotherapy.
The clinical benefit rate was 67% overall and 72% for patients who had already received platinum chemo.
In the 14 responders, median duration of response was 10 months, with ongoing responses in nine patients at data cutoff.
Median progression-free survival was 8.3 months for response evaluable patients, and 8,6 months in those previously treated with platinum chemo.
In a briefing ahead of ASCO J&J pointed out that PFS is typically around 3.7 months in this patient group.
As there are no approved targeted therapies for this kind of lung cancer, the FDA has granted Breakthrough Therapy status to amivantamab in this form of lung cancer earlier this year.

an hour ago
Seeking novel therapies from the patient’s perspective
Seeing a lot of positive comments about the Lost in the Woods? presentation on seeking novel therapies from the patient’s perspective from Dr Mark Lewis, director of gastrointestinal oncology at Intermountain Healthcare.
His take home points:
–       Don’t underestimate tech-savvy, self-advocating patients
–       Physicians – teach patients to use
–       Driver mutations are breaking down traditional histopathologic boundaries
–       The past was ‘shotgun’ toxicity, the future is ‘sniper’ aim
–       Patients are our partners in progress
2 hours ago
ASCO verdict on BMS’ first line lung cancer combination
ASCO is saving its analysis of the ADAURA trial, the latest lung cancer data from AstraZeneca’s lung cancer drug Tagrisso (osimertinib) for its big plenary session in the afternoon.
But Benjamin Levy, clinical director of oncology at the Johns Hopkins Sidney Kimmel Cancer Center took us through the latest data from Bristol-Myers Squibb’s immunotherapy combination in first line lung cancer.
In the past few weeks BMS scored two FDA wins with the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) in first line lung cancer.
An approval in first-line non-small cell lung cancer offered patients with the PD-L1 biomarker present in at least 1% of tumour cells the option of a chemotherapy-free regimen.
The other approval gave the option of Opdivo and Yervoy plus doublet chemotherapy regardless of the presence of PD-L1.
Levy’s conclusion is that these do offer two new options, although he cited concerns about the toxicity profile of the combination without chemotherapy, which caused 12% of patients to quit.
He wants to see five year data to select the best regimen in what is becoming a quite crowded field, with Merck & Co’s Keytruda (pembrolizumab) still the main contender.
He concluded with a lesson learned from AstraZeneca’s Imfinzi (durvalumab), which failed in the MYSTIC trial in first line lung cancer in 2017,.
Levy noted a 2018 exploratory analysis of the data showed “competitive outcomes” based on the plasma tumour mutation burden biomarker.
According to Levy this shows the “need to move beyond PD-L1 and find better biomarkers.”

Thinking about thinking: lessons from the coronavirus

It’s been a rough few months for all of us—everyone, all over the whole world. I want to share a few thoughts on the coronavirus epidemic, politics, and what this reveals about human thinking.
For future reference, this is being written in late May 2020, and the U.S. is just now beginning to tentatively reopen after large sections of the country have been effectively quarantined. I’ve worked hard to be a relatively dispassionate observer of the developing dialog in the US, and, frankly, I’ve seen much that raises cause for concern. I’ll share some of these observations in a short series of blogs this week, and hopefully tie up with some ideas for how we can strengthen our rational abilities.
Though there’s always a lot going on, I see two critical influences in recent history:
  • Over the past 10-15 years, the rise of social media
  • Over the past 4-6 years, increasing political division, at least in the US and Europe
Let’s look at social media today, and we’ll consider the impact of politics in another post soon.

Social media

Social media is truly a mixed blessing. On one hand, we have easy interaction and some access to top experts in many fields. Of course, there are a host of people “hacking expertise” and pretending to be experts, but there’s at least the potential to access a richness and depth of thought that has never existed before.
However, from a practical perspective, this does not often happen, and the negatives often most strongly outweigh the positives.

Attention spans are cratering

For one thing, carefully engineered interfaces have changed human attention spans. We now click through stories and videos, sometime giving only a few seconds to snippets of information. This, of course, encourages the shallowest possible thinking, but the damage to our ability to focus may be catastrophic.
The best work humans can do is deep work, but how many people feel disconnected and disjointed today? How many people can sit down and focus on a task for hours? Is this different than it was just a decade ago? Where will we be ten years from now if this doesn’t change?
(As an aside, if you’re looking for hard research on this subject, the jury is still out. You can find studies that support what I’m saying, but other studies raise questions about methodology. Short answer is we don’t know, but I have a strong conviction, based on admittedly anecdotal evidence, that something is going on here.)

Find your echo chamber

One of the other issues in social media communities is that people tend to congregate in like-minded groups. Of course this makes sense, but is there a downside to being surrounded by people who think like you do?
You betcha. In reinforcing each other, these groups tend to defend their thinking. Good thinking means thinking about thinking—not an easy task. Confirmation bias works hard to “keep us in our lane” and blinds us to important pieces of information. In these small communities, the problem is often overwhelming.
Whether we realize it or not, our actions are the end result of evolution and tens of thousands of years of civilizations. Communities have existed to protect us from outsiders, from the proverbial barbarians coming over the hills. I worry this is misfiring in the social media environment, where communities so often insulate us from opinions and perspectives other than our own.
It might feel good to be in a group of people who agree with you, but being our best selves is often about being at least a little bit uncomfortable.

Constant emotional manipulation

It’s not about how we feel. Or is it?
Actually, social media engages in the war for our attention through primarily emotional means. Stories, pictures, and clickbait headlines are designed to grab attention and manipulate passions. Interactions on social media tend to go to “full on road rage” in seconds, perhaps because it’s easy to forget we are interacting with an actual human behind those glowing words on a screen.
How often have you seen an apparently rational person go off the deep end in just a few social media interchanges? It’s not unusual to see physical violence threatened, just because someone disagrees with an opinion. We could never get away with this in actual society, but social media is a great unknown, and that great unknown is a land of dialed up emotions and, often, dialed back reason.
That’s a good place to leave this today. In my next post, we’ll dig a little bit deeper into reason and emotion, and think about the part political beliefs play in this.


Thinking about thinking: lessons from the coronavirus

State-Based Contact Tracing Apps Could Be a Mess

While governments around the world have launched nationwide Covid-19 contact-tracing smartphone apps over the last months, the US pointedly has not. Instead, it seems like the apps designed to detect coronavirus exposure stateside will launch on a state-by-state basis—and they may be anything but united.
When Google and Apple officially launched their exposure notification API for Android and iOS last week, their announcement included statements from three states—Alabama, North Dakota, and South Carolina—that are already building apps that will integrate the company’s Bluetooth-based system.
But it increasingly seems that neither the Centers for Disease Control and Prevention, nor the Department of Health and Human Services, nor any other US federal agency will release a nationwide coronavirus contact tracing app. “There is no effort I know of at the national level to build anything” like a contact tracing app, says someone familiar with the White House Covid-19 task force deliberations led by President Donald Trump’s son-in-law Jared Kushner, speaking to WIRED under the condition of anonymity. “Just like you’ve seen with the plan on testing and reopening, it’s being pushed to the states.”
Another adviser to that task force, Andy Slavitt, who led Medicare and Medicaid policy in the Obama administration and reportedly offered recommendations to Kushner, tells WIRED that any contact-tracing smartphone apps are almost certain to be left to the states alone. “I don’t think the federal government wants the responsibility to figure out the best and most efficient way to execute a contact tracing app,” says Slavitt. “If it’s like everything else they’re doing, they’re going to want to make sure the states have the responsibility.” Neither the CDC nor the HHS responded to WIRED’s request for comment about any plans to launch a national Covid-19 tracking or notification app.
“If this is getting done on a state-by-state level or even a confederacy of states, like the Western Pact, the question is then around security and interoperability,” says Ashkan Soltani, the former lead technologist for the Federal Trade Commission, who has been analyzing Covid-19 tracing and notification apps. “If each state is trying to put this together, you run the risk of commercial entities building this, the systems’ backends not being secure, and reliability issues.”
The potential for privacy disasters from contact tracing apps already have been well demonstrated. North Dakota’s app was found to be sharing data with Foursquare and Google’s advertising system. India’s contact tracing app made it possible to locate some Covid-19-infected users by spoofing GPS locations. And a flaw in Qatar’s contact tracing system leaked hundreds of thousands of users’ personal data, including health status and locations.
Rather than auditing one national app for security and privacy issues, Soltani says, every state-level contact tracing or exposure notification system will have to be individually vetted for those sorts of issues. And for each one, the devil will be in the details of its implementation.
Google and Apple’s Bluetooth-based system, for instance, offers app makers a relatively privacy-preserving approach: It doesn’t collect any location information from phones, and doesn’t even collect any information at all from the phones of users who don’t voluntarily mark themselves as having been diagnosed as Covid-19 positive. For the vast majority of users, no information is ever uploaded to the server of the organization running the app.
But when a Covid-19 patient self-reports as positive through the system, their apps upload a set of rotating codes that their phones have transmitted to other users via Bluetooth for the previous two weeks. While those codes aren’t identifying in themselves, every app maker will have to take care not to collect the IP addresses of those Covid-19 patients’ smartphones, which could be used to identify infected individuals. Or if they do collect those IP addresses—say, to prevent denial of service attacks on their servers—they’ll have to be careful not to keep the data for too long or allow it to leak.
Those sorts of implementation issues only become more critical if some states choose to use other systems that, unlike the one designed by Google and Apple, instead collect location information—as the contact tracing app launched in the state of Utah does. That could potentially leave state agencies responsible for protecting sensitive information about the movements of millions of people. “I definitely don’t trust 50 different state health departments to do this as reliably as one federal agency,” says Matthew Green, a cryptographer at Johns Hopkins who has analyzed the security of contact tracing and exposure notification apps.
More fundamentally, Green argues, a state-by-state approach raises the potential for states to use different, incompatible systems, so that Covid-19 exposure events might be missed if a user crosses state lines. “If I’m in New York and a lot of people are coming in from New Jersey, it seems like it’s going to be a big problem,” he adds. “It’s the opposite of a network effect.”
Green notes that if two states’ apps are both using Google and Apple’s protocol, that interoperability problem becomes more manageable. The two states simply share the unique codes that have been uploaded by Covid-19 positive users, so that people who have come into Bluetooth proximity with them in either state can be warned. Apple and Google have even suggested that multiple states’ apps could be designed to run on the same backend server infrastructure.
But that interoperability falls apart if one state, like Utah, opts for a location-based system, while others are using a Bluetooth-based one—or even if one state is using a decentralized Bluetooth-based system like the Google and Apple system, while another deploys a centralized model implemented by countries like Australia and Singapore. “It’s very easy to make decentralized apps interoperable,” says Cristina White, a Stanford professor and executive director of the decentralized exposure notification system CovidWatch. “If everyone is doing different things, with some decentralized and some centralized, and everyone’s using different protocols, that’s harder.”
Another contact-tracing app project, the MIT spinoff nonprofit Pathcheck, says it’s currently in talks with a dozen states or “jurisdictions”—multistate regions—about rolling out contact tracing or exposure notification apps for those areas. But MIT professor Ramesh Rashkar, one of the group’s founders, says that most of the agencies he’s talked to have expressed more interest in location-based contact tracing apps than in the Bluetooth-based system developed by by Google and Apple. And he concedes that could create interoperability issues until a standard is established. “My expectation is that in the immediate version, there’ll be a mess with the respect to interoperability, but that it will get fixed as we deploy more solutions,” adds Rashkar.
Contact tracing and exposure notification apps, regardless, represent at best one tool that can help Americans return to normal life. Slavitt, the Obama-era health care czar, says that, for instance, he sees the apps as “between 10 and 20 percent” of a larger picture depending far more on manual contact tracing and widespread testing.
But now, with no nationwide app in the US, fragmentation threatens to become another hurdle to even such a relatively modest role for Covid-19 alert and tracking apps. Until states can agree on a standard or build interoperability between their systems, every line on the US map could represent another constraint on a technology that might otherwise help chip away at the global pandemic’s effects.

Protesters increase the risk of getting, spreading coronavirus: officials

Protesters flooding streets across America are putting themselves at risk of catching the coronavirus — and likely exacerbating its ongoing spread, officials have warned.
“If you were out protesting last night, you probably need to go get a COVID test this week,” Atlanta Mayor Keisha Lance Bottoms warned those taking to the streets in her city.
Bottoms was one of many to note the dangers of thousands suddenly ignoring any form of lockdown or social distancing to protest George Floyd’s caught-on-camera death in police custody.
She stressed that “there is still a pandemic in America that’s killing black and brown people at higher numbers.”
Health experts fear that silent carriers of the virus who have no symptoms could unwittingly infect others at protests where people are packed cheek to jowl, many without masks.
Even those with masks are not guaranteed protection, with the Centers for Disease Control and Prevention (CDC) saying cloth masks are more for stopping infected people spreading the virus than protecting the wearer.
“Whether they’re fired up or not, that doesn’t prevent them from getting the virus,” warned Bradley Pollock, chairman of the Department of Public Health Sciences at the University of California, Davis.
The protests are almost certainly going to fuel infections and damage efforts to contain the pandemic through lockdowns and tightly organized social distancing, Minnesota’s health commissioner warned.
“We have two crises that are sandwiched on top of one other,” said Jacob Frey, the mayor of Minneapolis where Floyd died during the Memorial Day arrest.
The ongoing protests come as the US has seen more than 1.7 million confirmed coronavirus cases with 103,781 deaths, according to a tally by Johns Hopkins University.

Russia OKs flu drug for COVID-19

Russia’s Ministry of Health has approved an off-patent pill, originally sold under the brand name Avigan for influenza by a unit of Fujifilm Holdings (OTCPK:FUJIF), for the treatment of hospitalized COVID-19 patients.
Early tests showed that the antiviral, favipiravir, shortened recovery time. In the first randomized trial, 65% (n=26/40) of treated patients tested negative for the virus within five days, about half the time it took untreated patients to recover. It works by interfering with the ability of RNA viruses to replicate.
Western scientists say they want to review the data before judging whether other countries should add the med to their COVID-19 armamentaria.
Investigators in Japan and China are currently testing favipiravir’s effect on the coronavirus. The former’s trial sites include three locations in Massachusetts. The White House has indicated a keen interest in pushing its use in the U.S.
Gilead Sciences’ (NASDAQ:GILD) remdesivir, OK’d by the FDA for emergency use on May 1, is an injectable and remains the only drug approved thus far in America for for the respiratory disease.

Amazon scales back deliveries near protests

As the death of George Floyd sparks demonstrations across the country, Amazon (NASDAQ:AMZN) is scaling back deliveries and adjusting routes in a number of cities including Chicago, Los Angeles and Portland.
The e-commerce giant is “in close contact with local officials” and will only reopen delivery stations when it can “ensure the safety of our teams.”

Coronavirus May Be a Blood Vessel Disease, Which Explains Everything

In April, blood clots emerged as one of the many mysterious symptoms attributed to Covid-19, a disease that had initially been thought to largely affect the lungs in the form of pneumonia. Quickly after came reports of young people dying due to coronavirus-related strokes. Next it was Covid toes — painful red or purple digits.
What do all of these symptoms have in common? An impairment in blood circulation. Add in the fact that 40% of deaths from Covid-19 are related to cardiovascular complications, and the disease starts to look like a vascular infection instead of a purely respiratory one.
Months into the pandemic, there is now a growing body of evidence to support the theory that the novel coronavirus can infect blood vessels, which could explain not only the high prevalence of blood clots, strokes, and heart attacks, but also provide an answer for the diverse set of head-to-toe symptoms that have emerged.
“All these Covid-associated complications were a mystery. We see blood clotting, we see kidney damage, we see inflammation of the heart, we see stroke, we see encephalitis [swelling of the brain],” says William Li, MD, president of the Angiogenesis Foundation. “A whole myriad of seemingly unconnected phenomena that you do not normally see with SARS or H1N1 or, frankly, most infectious diseases.”
“If you start to put all of the data together that’s emerging, it turns out that this virus is probably a vasculotropic virus, meaning that it affects the [blood vessels],” says Mandeep Mehra, MD, medical director of the Brigham and Women’s Hospital Heart and Vascular Center.
In a paper published in April in the scientific journal The Lancet, Mehra and a team of scientists discovered that the SARS-CoV-2 virus can infect the endothelial cells that line the inside of blood vessels. Endothelial cells protect the cardiovascular system, and they release proteins that influence everything from blood clotting to the immune response. In the paper, the scientists showed damage to endothelial cells in the lungs, heart, kidneys, liver, and intestines in people with Covid-19.
“The concept that’s emerging is that this is not a respiratory illness alone, this is a respiratory illness to start with, but it is actually a vascular illness that kills people through its involvement of the vasculature,” says Mehra.
A respiratory virus infecting blood cells and circulating through the body is virtually unheard of.

A one-of-a-kind respiratory virus

SARS-CoV-2 is thought to enter the body through ACE2 receptors present on the surface of cells that line the respiratory tract in the nose and throat. Once in the lungs, the virus appears to move from the alveoli, the air sacs in the lung, into the blood vessels, which are also rich in ACE2 receptors.
“[The virus] enters the lung, it destroys the lung tissue, and people start coughing. The destruction of the lung tissue breaks open some blood vessels,” Mehra explains. “Then it starts to infect endothelial cell after endothelial cell, creates a local immune response, and inflames the endothelium.”
A respiratory virus infecting blood cells and circulating through the body is virtually unheard of. Influenza viruses like H1N1 are not known to do this, and the original SARS virus, a sister coronavirus to the current infection, did not spread past the lung. Other types of viruses, such as Ebola or Dengue, can damage endothelial cells, but they are very different from viruses that typically infect the lungs.
Benhur Lee, MD, a professor of microbiology at the Icahn School of Medicine at Mount Sinai, says the difference between SARS and SARS-CoV-2 likely stems from an extra protein each of the viruses requires to activate and spread. Although both viruses dock onto cells through ACE2 receptors, another protein is needed to crack open the virus so its genetic material can get into the infected cell. The additional protein the original SARS virus requires is only present in lung tissue, but the protein for SARS-CoV-2 to activate is present in all cells, especially endothelial cells.
“In SARS1, the protein that’s required to cleave it is likely present only in the lung environment, so that’s where it can replicate. To my knowledge, it doesn’t really go systemic,” Lee says. “[SARS-CoV-2] is cleaved by a protein called furin, and that’s a big danger because furin is present in all our cells, it’s ubiquitous.”

Endothelial damage could explain the virus’ weird symptoms

An infection of the blood vessels would explain many of the weird tendencies of the novel coronavirus, like the high rates of blood clots. Endothelial cells help regulate clot formation by sending out proteins that turn the coagulation system on or off. The cells also help ensure that blood flows smoothly and doesn’t get caught on any rough edges on the blood vessel walls.
“The endothelial cell layer is in part responsible for [clot] regulation, it inhibits clot formation through a variety of ways,” says Sanjum Sethi, MD, MPH, an interventional cardiologist at Columbia University Irving Medical Center. “If that’s disrupted, you could see why that may potentially promote clot formation.”
Endothelial damage might account for the high rates of cardiovascular damage and seemingly spontaneous heart attacks in people with Covid-19, too. Damage to endothelial cells causes inflammation in the blood vessels, and that can cause any plaque that’s accumulated to rupture, causing a heart attack. This means anyone who has plaque in their blood vessels that might normally have remained stable or been controlled with medication is suddenly at a much higher risk for a heart attack.
“Inflammation and endothelial dysfunction promote plaque rupture,” Sethi says. “Endothelial dysfunction is linked towards worse heart outcomes, in particular myocardial infarction or heart attack.”
Blood vessel damage could also explain why people with pre-existing conditions like high blood pressure, high cholesterol, diabetes, and heart disease are at a higher risk for severe complications from a virus that’s supposed to just infect the lungs. All of those diseases cause endothelial cell dysfunction, and the additional damage and inflammation in the blood vessels caused by the infection could push them over the edge and cause serious problems.
The theory could even solve the mystery of why ventilation often isn’t enough to help many Covid-19 patients breathe better. Moving air into the lungs, which ventilators help with, is only one part of the equation. The exchange of oxygen and carbon dioxide in the blood is just as important to provide the rest of the body with oxygen, and that process relies on functioning blood vessels in the lungs.
“If you have blood clots within the blood vessels that are required for complete oxygen exchange, even if you’re moving air in and out of the airways, [if] the circulation is blocked, the full benefits of mechanical ventilatory support are somewhat thwarted,” says Li.
A new paper published last week in the New England Journal of Medicine, on which Li is a co-author, found widespread evidence of blood clots and infection in the endothelial cells in the lungs of people who died from Covid-19. This was in stark contrast to people who died from H1N1, who had nine times fewer blood clots in the lungs. Even the structure of the blood vessels was different in the Covid-19 lungs, with many more new branches that likely formed after the original blood vessels were damaged.
“We saw blood clots everywhere,” Li says. “We were observing virus particles filling up the endothelial cell like filling up a gumball machine. The endothelial cell swells and the cell membrane starts to break down, and now you have a layer of injured endothelium.”
Finally, infection of the blood vessels may be how the virus travels through the body and infects other organs — something that’s atypical of respiratory infections.
“Endothelial cells connect the entire circulation [system], 60,000 miles worth of blood vessels throughout our body,” says Li. “Is this one way that Covid-19 can impact the brain, the heart, the Covid toe? Does SARS-CoV-2 traffic itself through the endothelial cells or get into the bloodstream this way? We don’t know the answer to that.”
In another paper that looked at nearly 9,000 people with Covid-19, Mehra showed that the use of statins and ACE inhibitors were linked to higher rates of survival.

If Covid-19 is a vascular disease, the best antiviral therapy might not be antiviral therapy

An alternative theory is that the blood clotting and symptoms in other organs are caused by inflammation in the body due to an over-reactive immune response — the so-called cytokine storm. This inflammatory reaction can occur in other respiratory illnesses and severe cases of pneumonia, which is why the initial reports of blood clots, heart complications, and neurological symptoms didn’t sound the alarm bells. However, the magnitude of the problems seen with Covid-19 appear to go beyond the inflammation experienced in other respiratory infections.
“There is some increased propensity, we think, of clotting happening with these [other] viruses. I think inflammation in general promotes that,” Sethi says. “Is this over and above or unique for SARS-CoV-2, or is that just because [the infection] is just that much more severe? I think those are all really good questions that unfortunately we don’t have the answer to yet.”
Anecdotally, Sethi says the number of requests he received as the director of the pulmonary embolism response team, which deals with blood clots in the lungs, in April 2020 was two to three times the number in April 2019. The question he’s now trying to answer is whether that’s because there were simply more patients at the hospital during that month, the peak of the pandemic, or if Covid-19 patients really do have a higher risk for blood clots.
“I suspect from what we see and what our preliminary data show is that this virus has an additional risk factor for blood clots, but I can’t prove that yet,” Sethi says.
The good news is that if Covid-19 is a vascular disease, there are existing drugs that can help protect against endothelial cell damage. In another New England Journal of Medicine paper that looked at nearly 9,000 people with Covid-19, Mehra showed that the use of statins and ACE inhibitors were linked to higher rates of survival. Statins reduce the risk of heart attacks not only by lowering cholesterol or preventing plaque, they also stabilize existing plaque, meaning they’re less likely to rupture if someone is on the drugs.
“It turns out that both statins and ACE inhibitors are extremely protective on vascular dysfunction,” Mehra says. “Most of their benefit in the continuum of cardiovascular illness — be it high blood pressure, be it stroke, be it heart attack, be it arrhythmia, be it heart failure — in any situation the mechanism by which they protect the cardiovascular system starts with their ability to stabilize the endothelial cells.”
Mehra continues, “What we’re saying is that maybe the best antiviral therapy is not actually an antiviral therapy. The best therapy might actually be a drug that stabilizes the vascular endothelial. We’re building a drastically different concept.”