New Decoy Protein Treatment Fools Coronavirus, Rendering It Impotent

 A novel decoy protein designed by Northwestern Medicine scientists fools SARS-Cov-2  by intercepting the spike of the coronavirus and rendering it impotent.

The novel protein significantly reduced lung damage and resulted in only mild symptoms in mice infected with SARS-Cov-2, while untreated animals in this model all succumbed to the infection.

“We envision this soluble ACE2 protein will attenuate the entry of coronavirus into cells in the body mainly in the respiratory system and, consequently, the serious symptoms seen in severe COVID 19,” said lead investigator Dr. Daniel Batlle, a professor of medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “We have converted a lethal disease to a milder lung disease that is fully reversible. The protein could be complimentary to other potential treatments or effective alone.”

The protein is a variant of ACE2 (angiotensin converting enzyme-2), the receptor the coronavirus uses to enter and infect human cells. The modified protein intercepts the S spike of the coronavirus and fools it into binding to it rather than the real ACE2 receptor in cell membranes.

The study is the first proof of concept that a soluble human ACE2 protein is effective in vivo in a preclinical study using an appropriate animal model. The soluble ACE2 protein variant developed by Batlle and colleagues binds well to the coronavirus and has been enhanced so it’s effective for days. 

“While widespread vaccination is the best way to combat the COVID-19 pandemic, there will always be a need for treatment of people who were not vaccinated or for whom the vaccine was not fully effective,” Batlle said.

The study is a pre-print, which means the findings should be considered preliminary until it is published in a peer-reviewed journal. 

Investigators tested the protein in a genetically modified mouse model, because normal rodents are resistant to infection by the coronavirus causing COVID-19. Mouse ACE2 does not bind the coronavirus. But the transgenic mouse can be infected by the coronavirus, because in addition to its own mouse ACE2 it also has human ACE2 in its tissue.

Batlle’s lab has studied ACE2 for many years as part of a potential treatment for kidney disease. Batlle and study co-author Dr. Jan Wysocki, research assistant professor of medicine at Feinberg, have bioengineered novel ACE2 variants licensed to Northwestern University. They believe the variants can be adapted for COVID-19 therapy by intercepting the coronavirus and preventing it from attaching to the natural ACE2 receptor in the membrane of the cell.

The next steps involve the planning of safety studies needed before applying for Investigational New Drug approval for future studies in patients with COVID-19.

The study was supported in part by the Joseph and Bessie Feinberg Foundation, a gift from the state of Dr. Frank Krumlowsky and the George M. O’Brien Kidney Research Core Center (NU GoKidney) supported by the award P30 DK114857 (National Institute of Diabetes and Digestive and Kidney Diseases). Dr. Batlle received unrelated support from grant RO1DK104785 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

https://scitechdaily.com/new-decoy-protein-treatment-fools-coronavirus-rendering-it-impotent/

340B Drug Discount Program Should Be on GAO’s High-Risk-for-Abuse List

 When a new Congress begins, the Government Accountability Office (GAO) releases its updated “High-Risk List” of programs and operations that are ‘high risk’ due to their vulnerabilities to fraud, waste, abuse, and mismanagement, or that need transformation. The 2021 version has 36 risk areas, including Department of Defense (DOD) Weapons Systems Acquisition, Medicare and Medicaid, and the National Flood Insurance Program.

While improvements were seen in seven areas, the only program removed was the DOD Support on Infrastructure Management, which had been on the list since 1997. Overall, the ratings for 20 of the 36 areas remained unchanged, with five areas that regressed. The GAO added Small Business Administration Emergency Loans and the Federal Response to Illegal Drug Use to the list. However, the 340B Drug Discount Program, which has been the subject of several critical GAO reports, should also have been added to the list. 

GAO reports on 340B include “Medicare Part B Drugs: Action Needed to Reduce Financial Incentives to Prescribe 340B Drugs at Participating Hospitals,” which was published in 2015 and found that on average Part B spending at 340B disproportionate share hospitals (DSH) was higher than non-340B hospitals, likely because more drugs were prescribed or more expensive drugs were dispensed. A 2018 report found insufficient oversight by the Health Resources and Services Administration (HRSA) with regard to contract pharmacies’ accountability to ensure compliance with the program, like verifying prohibited duplicate discounts were not being provided for Medicaid beneficiaries. The House Energy and Commerce Committee issued a report in January 2018 that laid out several recommendations to improve the program, like clarifying its intent, promoting more transparency for all stakeholders, requiring independent audits of program compliance, and establishing a mechanism to monitor levels of charity care.

Congress created 340B under the 1992 Veterans Health Care Act to fix a problem it had created when the Medicaid Drug Rebate program was established in 1990. The rebates were based on the average manufacturer price (AMP) or the difference between the AMP and the lowest price charged to any entity in the U.S. Although members of Congress were made aware of a problem related to discounts in hearings on the legislation, the bill that was enacted into law did not factor in the substantial voluntary discounts many pharmaceutical companies had given the VA and non-profit entities that were serving indigent and uninsured patients. As a result, their generous discounts disappeared. The 1992 law created two new price control programs, the VA Federal Ceiling Price program and the 340B Drug Discount Program and excluded their prices from the Medicaid rebate calculus.

The Patient Protection and Affordable Care Act (PPACA) expanded eligibility to more hospitals, like sole community and critical access hospitals, along with expanded Medicaid eligibility.

This was one of several reasons why the 340B has grown wildly out of control with an increase of 464 percent since 2010. It has also been subject to significant waste, abuse, and mismanagement. In addition to the PPACA expansion, HRSA allowed covered entities to have unlimited for-profit contract pharmacies, including chain drug stores, to participate in the program even though the law is silent on the use of contract pharmacies. Because there is no requirement to pass along the savings to the patient, hospitals and their contract pharmacies can pocket the difference between the 340B discounted price and what insurance pays.

In 2018, the New England Journal of Medicine found that there are no direct incentives for 340B DSH hospitals to follow the intent of the program and use the savings to improve care for low-income patients who need it most. The 340B program has been associated with “hospital-physician consolidation in hematology-oncology” that has led to more “hospital-based administration of parenteral drugs” like cancer drugs, but the financial gains for hospitals “have not been associated with clear evidence of expanded care or lower mortality among low-income patients.”

Despite these findings and recommendations, nothing has been done to reform 340B and stop hospitals and for-profit pharmacies from enriching themselves. Establishing a clear definition for a 340B patient by focusing on indigent individuals with no health insurance would go a long way in solving many of the problems in the program. It is long past due to be put on the 340B program on the GAO High Risk List and for Congress to return it to its original mission.

Elizabeth Wright is the Health and Science Director at Citizens Against Government Waste

https://www.realclearhealth.com/articles/2021/04/02/340b_drug_discount_program_should_be_on_gaos_high-risk_list_111186.html

Mass General team uncovers 13 new Alzheimer's gene variants

 Massachusetts General Hospital’s Rudolph Tanzi, Ph.D., is well known in the Alzheimer’s field for co-discovering genes that, when mutated, cause early-onset disease. Now, his lab is announcing the discovery of 13 additional gene variants that are associated with the brain disorder—and that may inspire new therapies.

A team led by Mass General used whole-genome sequencing to uncover rare genetic variants associated with Alzheimer’s. The 13 newly discovered mutations affected synapses that transmit signals between neurons as well as neuroplasticity, which is the ability of neurons to organize a network. The researchers reported their findings in the journal Alzheimer's & Dementia.

Alzheimer’s genes have typically been identified through genomewide association studies, which scan the genomes of patients to find variants that occur more frequently in them than they do in the general population. But this method rarely turns up uncommon variants.

So Tanzi’s team decided to perform whole-genome sequencing on 2,247 people from 605 families that had multiple members with Alzheimer’s. They also studied genomic data from an additional 1,669 people.

Tanzi and his colleagues had previously found gene mutations related to the buildup of amyloid in the brain—a hallmark of Alzheimer’s. They also discovered 30 variants related to brain inflammation. Tanzi even co-founded a company, Prana Biotechnology, that sought to reduce amyloid in the brain by balancing zinc and copper, but the drug failed in phase 2 trials. (Prana since changed its name to Alterity Therapeutics.)

Tanzi believes the 13 newly discovered variants could be vital, because they provide the first genetic links between Alzheimer’s and the loss of synapses and neuroplasticity.  

"With this study, we believe we have created a new template for going beyond standard [genome-wide association studies] and association of disease with common genome variants, in which you miss much of the genetic landscape of the disease," said Tanzi, vice chair of neurology and director of Mass General’s genetics and aging research unit, in a statement.

Tanzi and his co-researchers have developed 3D cell cultures and brain organoids that mimic Alzheimer’s. They are now planning to use those tools to study how neurons that have any of the 13 newly discovered mutations behave. They believe their discoveries could point the way to novel drugs to treat the disease.

https://www.fiercebiotech.com/research/mass-general-team-uncovers-13-new-alzheimer-s-gene-variants

UK To Roll Out 'Covid Passports' For Sporting And Music Events

 As we have reported numerous times, the reality of COVID-19 passports will become an individual's 'passport to life' seems like a foregone conclusion. The UK intends to roll out "Covid passports" within weeks for high-profile sporting and music events. 

Those who are wealthy and/or fortunate enough to get their hands on the vaccine may be able to attend FA Cup semi-finals and final as well as the League Cup final in football and the World Snooker Championship, along with numerous music events, according to FT. 

Pilot tests for "coronavirus-free" mass events will require anyone entering the event to provide digital Covid certificates, including vaccination history or a recent test. The first trial run of the digital Covid passport for the mass gathering will begin this summer. 

The "digital certification app" will be found inside the National Health Service's existing app used by patients to book doctor appointments and order prescriptions. COVID passports for mass gatherings may be announced as soon as this week, or early next week. 

Prime Minister Boris Johnson has already suggested health passports may be required for entry to pubs and restaurants. This means that citizens will have to produce "papers for the pub" — which could be included as part of recommendations in a report for combatting the spread of Covid, which is due out in May. 

Cabinet Office minister Michael Gove examined the legal and ethical issues around COVID passports for pubs, restaurants, and other mass gathering areas. 

COVID passport plans have already been met with fierce opposition from more than 70 members of Parliament across various political parties. 41 Tory backbenchers warned such requirements would erode civil liberties.

One Tory MP said the possible requirements for health passports are "disgusting." 

None of this should be surprising to readers who have understood from our writings vaccination passports will be the new "golden ticket" for global travel, along with the travel and tourism industries and now other forms of mass gatherings such as sporting and music events. 

It's not just European countries that are rolling out COVID passports. The US is already in the process of leveraging apps and smartphones to allow travelers to offer proof that they have been vaccinated or recently tested negative for COVID-19.

MSNBC's Joe Scarborough, a frequent and early GOP critic of former President Trump, called any American who didn't support vaccine passports "an idiot." 

The thought is health passports could stimulate an economic recovery as countries prepare to relax public health measures. Still, the trade-off is that people must hand over more and more of their health credentials to governments and corporations. 

https://www.zerohedge.com/covid-19/uk-roll-out-covid-passports-sporting-and-music-events

Big U.S. Companies Added Jobs in 2020 -- Thanks to Amazon

 While Covid-19 ravaged the broader American economy, the largest U.S. employers added more jobs than they cut.

Overall, global employment rose by about 370,000 people among the 286 members of the S&P 500 that filed annual reports between July 1 and March 31, a Wall Street Journal analysis of securities filings shows.

Those gains masked wrenching changes and job losses for workers in many companies and industries. And the net gain in jobs for 2020 wouldn't have happened without a single company: Amazon.com Inc.

The giant internet retailer added 500,000 workers around the world during the year -- more than 400,000 of them in the U.S. Amazon created nearly as many jobs last year as the 136 other companies in the Journal analysis that added workers.

"By hiring that many people, we were not only able to deliver essential items for our customers during a critical time, but also provide an opportunity to those who lost their jobs or saw their hours cut because of Covid," said Beth Galetti, Amazon's senior vice president for human resources. "Amazon became an 'employment beacon' for hundreds of American communities." Workers at an Amazon warehouse in Alabama are voting on whether to unionize.

The overall U.S. labor market is healing from the pandemic's shocks. Employers added 916,000 jobs in March, the biggest gain since August. The unemployment rate fell to 6.0%.

The figures in the Journal analysis reflect global employment. Most firms don't disclose U.S. employment. Companies don't always disclose whether staffing changes stem from layoffs, attrition, deal making or other factors.

For example, PepsiCo Inc.'s addition of 24,000 jobs last year -- a 9% increase over 2019 -- was largely driven by acquisitions, including SodaStream International Ltd. About 1,300 of Costco Wholesale Corp.'s 19,000 new jobs came from the acquisition last year of what is now Costco Logistics, Chief Financial Officer Richard Galanti said.

Among companies adding workers, the median increase was 6.6%. Facebook Inc.'s workforce grew by 30%, or almost 14,000 jobs. Biotech giant Biogen Inc. added 1,700 workers, about 23%.

FedEx Corp.'s staffing increase of 50,000, or 11% -- which reflects the fiscal year that ended last May -- was driven in large part by sharply higher demand for e-commerce, a spokesman said.

In all, 133 companies in the Journal analysis shrank their workforces. Among them, the median decline was 5.1%, and a dozen companies lost a quarter or more of their workers. Eighteen reduced their head count by at least 10,000 people.

Deal making resulted in shrinking some workforces. Raytheon Technologies Corp. and United Technologies Corp. employed 313,200 in 2019, before merging last year and spinning off Otis Worldwide Corp. and Carrier Global Corp. The spinoffs ended 2020 with a combined 125,000 workers; Raytheon employed 181,000 on Dec. 31.

About a fifth of the 31,000 workers that General Electric Co. shed last year went with the sale of its lighting and biotechnology-supply divisions. Aluminum maker Arconic Inc. employed 41,700 in 2019, before splitting into two companies in April 2020: Howmet Aerospace Inc., employing 19,700, and Arconic Corp., employing 13,400, as of Dec. 31.

The pandemic also took its toll. Marriott International Inc. staff plummeted with the decrease in hotel stays. After sailings were suspended, Carnival Corp. shed 34,000 cruise-ship workers, more than a third of its total, while onshore staff declined by 2,000, or about 14%. Most of Comcast Corp.'s declines came at its NBCUniversal unit, which curtailed its theme-park operations for most of the year and underwent a reorganization in the fall. United Airlines Holdings Inc. early this year hired back about 13,000 of the 21,600 workers idled in 2020, but the company said that relief would likely end once federal aid runs out this spring.

More broadly, job losses fell unevenly across sectors. Most tech and healthcare companies added workers; no energy company in the Journal analysis did.

Longer-term trends continued to play out as well. Electric-car maker Tesla Inc. added about 22,700 workers during the year -- handily exceeding the loss of workers reported by larger Detroit rivals Ford Motor Co. and General Motors Co.

A GM spokesman said the company is investing heavily in electric vehicles and plans to add about 2,200 jobs in Michigan and 1,400 to 1,700 in Ontario as it reopens and retools plants, including some that will produce electric vehicles.

A Ford spokesman said the company is in the process of refocusing and streamlining its business to modernize and simplify operations, including for electric-vehicle production.

Even within an industry, employment moves varied. Casino chain Las Vegas Sands Corp. reported an 8% decline in its workforce. At MGM Resorts International, which employed significantly more people in 2019, head count fell by 36%.

With more than 20 casinos in the U.S., including a dozen on the Las Vegas Strip, MGM is more exposed to the hard-hit American economy, as well as to tourist travel in the U.S. By contrast, Las Vegas Sands has increasingly focused on foreign markets, generating nearly half its 2020 revenue in Macau and a third in Singapore -- and in early March said it would sell off its remaining U.S. properties.

In MGM's proxy statement filed March 26, Chief Executive Bill Hornbuckle called the company's widespread layoffs and furloughs painful but necessary as the Las Vegas Strip shut down and international gambling travel slowed. "We're optimistic that business will continue picking up and allowing for us to call back and hire a significant number of employees," an MGM spokesman said.

Companies hit hard by the pandemic tended to cut more jobs, but workforce changes and company results didn't always move together.

Fastenal Co., which distributes bolts and supplies for construction and industry, reduced its workforce by nearly 1,600 people during the year, or 7.2%. Profit rose 8.6% and shareholders booked a 36.6% total return, including share-price appreciation and dividends.

Much of that staffing decline involved part-time workers, with full-time employment falling just 2.5% as health restrictions and reduced demand idled distribution hubs and other operations, said Holden Lewis, Fastenal's chief financial officer. Many of the part-timers were out-of-town students who went home when their colleges closed, he added. And managers didn't fill jobs as employees left.

"We leave decisions in the field around head count -- what happens in any downturn is they wind up letting attrition work for them," Mr. Lewis said. He said headquarters urged managers to retain workers where possible.

At the same time, Fastenal's financial results benefited as it supplied face masks, gloves and other protective gear to existing and new customers, bypassing its usual distribution network to ship directly to customers in the interest of speed, he said.

Last spring, "we had no idea what our financials would look like, but we thought they were going to be a lot worse than they were," Mr. Lewis said. "We believe we operated with the integrity of spirit that I think companies in our position should have."

https://www.marketscreener.com/quote/commodity/LME-ALUMINIUM-CASH-16159/news/Big-U-S-Companies-Added-Jobs-in-2020-Thanks-to-Amazon-32883613/

J&J Covid-19 Vaccine Emerges as Preferred Shot for Homeless

 Johnson & Johnson's Covid-19 vaccine has found a niche among organizations that work with the homeless, who say the one-dose shot is better-suited for a population that can be difficult to reach twice.

The U.S. homeless population has soared during the pandemic. Shelters have become a source of spread as experts puzzle over how to stem stubbornly high infection rates despite an aggressive national vaccine rollout.

In Chicago, the Night Ministry, a group that serves the homeless, has increasingly used the J&J vaccine since it was approved by U.S. regulators in late February. Before that the group had only the Moderna Inc. vaccine, which requires two shots. But the often-transient population can be tough to find a second time, said Stephan Koruba, a nurse practitioner with the Night Ministry, especially those sleeping on the Chicago Transit Authority train system. Now, the group offers both.

"When we're out on the CTA, we're never going to see these people again, " Mr. Koruba said. "We've specifically held to J&J doses for them."

Many of the group's beneficiaries are living on the streets. Others in tent encampments. Or, for those able to pay a few hundred dollars a month to escape Chicago's frigid winter, in transient hotels.

Outside one such hotel, word spread recently that the Night Ministry had arrived, and people trickled out. As he prepared to administer the J&J vaccine, Nathan Lin, a medical resident working with the group, asked William Bryant, 67 years old, if he had a phone number. He responded that he didn't, pointing to his temporary residence above.

"Just right up there," Mr. Bryant said.

President Biden has set a goal of 200 million vaccines by April 30. About 162 million doses have been administered so far, data show, with the J&J vaccine representing about 3.8 million. The company faced a setback last week when one batch of the main ingredient for its vaccine didn't meet quality standards at a contract manufacturer, and the doses weren't distributed. J&J still plans to deliver a total of 100 million doses by the end of May.

Aside from Chicago, groups in California, Maryland and Tennessee are among those nationwide administering the J&J vaccines in encampments, shelters, and even on subways.

The number of people facing unstable housing and food scarcity has skyrocketed during the pandemic, said Salvation Army Commissioner Kenneth Hodder. The Salvation Army says it provided 1.8 million nights of shelter to people who said they needed it as a direct result of the pandemic.

Shelters and transient hotels became a source of spread around the country, according to city officials nationwide. The Salvation Army converted many of its thrift stores and administrative buildings into makeshift shelters to spread out the population. Those people were already dealing with other difficulties such as substance abuse, mental illness and comorbidities associated with poorer outcomes for Covid-19 infection.

"With respect to homelessness, we have seen a pandemic laid on top of an epidemic," Mr. Hodder said.

In the Chattanooga, Tenn., area, Christina Butler, a registered nurse and Covid-19 vaccine coordinator for the Hamilton County Health Department's Homeless Health Care Center, said the hardest part by far about getting people vaccinated is getting them the second shot. Ms. Butler said her group has been able to give a second dose to about 60% of recipients after extensive efforts to locate them on the street, at the community kitchen and at camps. Many people are now requesting the J&J shots, she added.

Some community workers have found pockets of resistance to the J&J vaccine among religious groups because it required the use of fetal cell cultures to produce and manufacture the vaccine. Some people said they were concerned that it was a less-effective, "poor person's shot."

Even so, healthcare workers say they have been surprised to find many homeless people specifically requesting the J&J vaccine, which is branded as Janssen, a unit of J&J. Some of them point out that the shot was still effective even though it was tested after Covid-19 variants entered the mix. Others say they are worried about getting a vaccine once, let alone twice, given the potential side effects.

"If you're in a shelter, or don't have a home, those side effects are different than if you can stay at home," said Bobby Watts, chief executive of the National Health Care for the Homeless Council, which supports hundreds of providers that cater to the homeless.

Nurse practitioner Mary Tornabene of Heartland Alliance Health in Chicago said that when her group received its first shipment of J&J shots, it offered both the J&J and Moderna doses at a meal program for people who mostly live on the street. Within 40 minutes, the J&J supply was used up while few had chosen the Moderna vaccine.

"They all wanted that," she said. "The thought for some people to get this shot once is hard enough, let alone twice."

The Night Ministry recently showed up where a Chicago encampment had been in place just days before to find that the people in it had been moved out by the city. The group had created a spreadsheet they had printed out and brought with them, with notes about how to find those who had received one dose of Moderna's vaccine. Locations included "tent city," or sometimes just a street corner, "Chicago and Sacramento."

Back at the transient hotel in Chicago, rooms have open ceilings -- like cubicles -- and bathrooms are shared. One man created a makeshift ceiling with plastic trash bags to protect himself from Covid-19, said Michael Bush, the hotel's manager. The hotel tries to circulate air with ceiling fans to minimize the risk of infection, he said. Others left the hotel to seek shelter elsewhere, adding to the challenge of locating those who had started a two-dose regimen, weeks after their first dose.

The Night Ministry managed to dispense a 10-dose vial of Moderna that recent day at the hotel, but on other days, with no viable way to make appointments, the group turned people away if there weren't enough takers to avoid wasting portions of a vial.

"We have some people making some very complicated calendars to try to map these shots out," said Adrienne Trustman, chief medical officer at Health Care for the Homeless in Baltimore, which is trying to move exclusively to J&J's one-dose regime. If not enough people show up for a second dose, they end up giving more first doses of the vaccine, adding to the list of people they need to track down for a second dose, she said. "When does it end?" she asked.

The five-dose J&J vial has changed everything, healthcare workers say.

"With Janssen, we can vaccinate twice as many people," Dr. Trustman said. "We have limited resources. And that math is pretty simple."

Outside the hotel, Rafael Fernandez, 41, walked up to the Night Ministry van to get a meal with his friend Dan Palmer, 35. He ended up being vaccinated after learning he would need only one shot.

https://www.marketscreener.com/quote/stock/JOHNSON-JOHNSON-4832/news/Johnson-Johnson-s-Covid-19-Vaccine-Emerges-as-Preferred-Shot-for-Homeless-32883632/

Troubling 'Eek' variant found in most Tokyo hospital COVID cases

 Around 70% of coronavirus patients tested at a Tokyo hospital last month carried a mutation known for reducing vaccine protection, Japanese public broadcaster NHK said on Sunday.

The E484K mutation, nicknamed “Eek” by some scientists, was found in 10 of 14 people who tested positive for the virus at Tokyo Medical and Dental University Medical Hospital in March, the report said.

For the two months through March, 12 of 36 COVID patients carried the mutation, with none of them having recently travelled abroad or reporting contact with people who had, it said.

Hospital officials were not immediately available for comment.

Ahead of the summer Olympics scheduled to begin in July, Japan is grappling with a new wave of infections. Health experts are particularly concerned about the spread of mutant strains, even as large-scale vaccinations of the general population have not yet begun.

On Friday, 446 new infections were reported in Tokyo, although that is still well below the peak of over 2,500 in January.

In Osaka, a record 666 cases were reported. Health experts have expressed concern about the spread around that western metropolis of a mutant strain known to have emerged in Britain.

NHK said none of the patients at the Tokyo hospital carried the British strain.

https://www.reuters.com/article/us-health-coronavirus-japan/troubling-eek-variant-found-in-most-tokyo-hospital-covid-cases-nhk-idUSKBN2BR03W