Minn. Gov Restricts Social Gatherings, Restaurants, Gyms, Youth Sports

 Minnesota Gov. Tim Walz has announced new COVID-19 restrictions that will impact social gatherings, restaurants, gyms and sports for four weeks.

The restrictions are in effect between Friday at 11:59 p.m. and Friday, Dec. 18. In-person social gatherings with people outside of your household are prohibited. Bars and restaurants will have to go take-out only. Gyms and entertainment spaces will need to close, and wedding receptions, private parties and celebrations will also be restricted. Adult and youth sports will be put on pause, but college and pro sports are exempt.

Schools will continue to operate under Walz’s Safe Learning Plan, which shifts students between in-person, distance and hybrid learning depending on the local spread of the virus.

Retail businesses and grocery stores will remain open at full capacity, while salons, barbershops and places of worship will stay open at half capacity.

All outdoor recreation areas like skating rinks, ski hills and parks can still operate, but their indoor areas will be closed.

Walz said that while the state has built up its bed capacity and supplies of personal protective equipment since the lockdown, doctors, nurses and other care staff are now increasingly falling ill because of community spread.

“I understand it’s not easy and it’s not fair,” Walz said. “But it’s a sacrifice that we need to make. If we don’t do that, and we continue to spread, we will with absolute certainty put our hospitals at risk, and those that need the care, as well as the care providers.”

Walz has said repeatedly that the decisions are based on data. Research shows that COVID spreads rapidly in places where people gather for extended periods of time, especially when they do not wear masks.

“I know the upcoming holidays make it incredibly difficult to stay home and stay apart, but this is how we keep the people we love safe and healthy,” Lt. Gov. Peggy Flanagan said. “Take it from me, no celebration is worth an empty seat that will never be filled.”

Originally, the restrictions began in March to prepare hospitals so that they could care for those ill with the virus. Now, months later, Walz says one of the major reasons for the new restrictions is because of the immense strain placed on health care workers.

Late Wednesday morning, Minnesota health officials reported 67 deaths due to COVID, and the state’s death toll crossed 3,000. The rate of hospitalizations has also never been higher; there were 27 hospitalizations per 100,000 residents as of Nov. 9.

It took 29 weeks to reach 100,000 infections in the state, and just six weeks after that to reach 200,000. The state projects it will hit the 300,000 case mark sometime next week.

“The velocity that this is moving now compared to any other time is simply stunning,” Walz said. “It would be easy to tell you this is going to be over but it is not. It’s going to be a very difficult four weeks.”

Walz also sent a letter Wednesday to Congressional leaders for federal aid.

https://minnesota.cbslocal.com/2020/11/19/coronavirus-restrictions-mn-gov-walz-announces-restrictions-on-social-gatherings-restaurants-gyms-and-youth-sports/

BeiGene's Xgeva OK'd in China for bone metastases due to cancer

• BeiGene's (NASDAQ:BGNE) XGEVA (denosumab) has been approved in China for the prevention of skeletal-related events in patients with bone metastases from solid tumors and in patients with multiple myeloma (MM).
• XGEVA is developed by Amgen (NASDAQ:AMGN) and licensed to BeiGene in China under a collaboration inked in October 2019 to develop cancer therapies.
• In October 2019, BeiGene in-licensed XGEVA from Amgen (AMGN).
• XGEVA targets the RANKL pathway to prevent the formation, function and survival of osteoclasts, which break down bone.
• https://seekingalpha.com/news/3638223-beigenes-xgeva-okd-in-china-for-bone-metastases-due-to-cancer

Plastic film used to protect foods and surfaces inactivates novel coronavirus

 Transparent stretchable PVC film for use in packaging meat, fruit, cold cuts, and other foods, and to protect surfaces, can inactivate the novel coronavirus.

Marketed by Brazilian plastics manufacturer Alpes, the material contains silver and silica nanoparticles, a technology developed and licensed by Nanox.

Nanox is a Brazilian company based in São Paulo, Brazil, and supported by FAPESP's Innovative Research in Small Business Program (PIPE).

In tests conducted at the Biosafety Level III (BSL-3) laboratory in the University of São Paulo's Biomedical Sciences Institute (ICB-USP), the PVC film proved capable of eliminating 79.9% of the particles of SARS-CoV-2 in three minutes and 99.99% in up to 15 minutes.

"Elimination of the virus by the material was extremely effective and fast. It's a very different application from the more than 40 products that attack the novel coronavirus tested by us since the start of the pandemic," said Lucio Freitas Junior, a researcher at ICB-USP.

The film was tested against ISO 21702:2019, the technical standard governing measurement of antiviral activity on plastic and other non-porous surfaces, and requiring demonstration of this capability within four hours.

Samples of the material with and without silver-silica nanoparticles were kept in direct contact with SARS-CoV-2 for varying amounts of time. After the stipulated periods, the viral particles found in the material were removed and placed in contact with Vero cells to measure the infection and replication rate after exposure to the film. Vero cells are derived from the kidney of an African monkey and widely used in microbiological cultures.

The viral genetic material was quantified by PCR, showing a reduction of almost 100% in copies of SARS-CoV-2 after 15 minutes of exposure to the film.

"Considering its use in wrapping for food products that are exposed and handled in supermarkets, 15 minutes for the film to eliminate the virus completely from the surface of the material is satisfactory," said Nanox CEO Luiz Gustavo Pagotto Simões.

Application in plastic

The stretch-wrap film is the third plastic material containing silver-silica nanoparticles to be marketed by Nanox to provide protection against COVID-19.

In partnership with toymaker Elka, the firm developed a reusable face-covering made of flexible thermoplastic material similar to rubber and coated with the additive as a surface layer. The mask promises to confer a higher level of protection against the novel coronavirus.

An adhesive plastic film containing the additive for protection of surfaces was launched in September by Promaflex and shown in testing to eliminate 99.84% of SARS-CoV-2 particles in two minutes.

The stretch-wrap film differs from the other two products in terms of the concentration of silver-silica nanoparticles in its composition. Given its use in food packaging, it has to contain a smaller amount of the additive.

"Our silver nanoparticles are registered with the FDA [US Food and Drug Administration] and whitelisted by ANVISA [Brazil's national health surveillance agency], which establish an upper limit on the amount that can be added to materials used as food packaging in order to ensure that the silver doesn't get into the food. So the concentration of the additive in this film has to be slightly lower," Simões explained.

Upgrades made by Nanox in recent years to the process whereby it produces ceramic nanoparticles with silver have enabled film manufacturers to improve the dispersion of the additive. As a result, the amount of silver can be much smaller, according to Simões. At the same time, the antimicrobial efficiency of the additive has been enhanced while maintaining transparency.

"PVC film must be very transparent. If the concentration of silver particles is high, the film can become yellow or gray. Our technology avoids this problem," he said.

The technology has proved effective to inactivate the novel coronavirus in other applications besides plastic-based products, such as fabric made of a blend of natural and synthetic fibers.

The additive has been used in apparel and fabric made by several Brazilian firms under license of the Nanox brand.

"We've also obtained good responses in studies to appraise the application of the solution in raw materials used by the construction industry, such as MDF in laminate flooring or paints," Simões said.

New markets

Alpes has marketed the plastic film with silver nanoparticles for food packaging to protect products against fungi and bacteria in supermarkets and the home since 2014. With the onset of the COVID-19 pandemic, it decided to see if the material could also eliminate SARS-CoV-2.

"Plastic film is considered a commodity, and the consumer's decision to buy is based mainly on price. By incorporating Nanox's additive, we aimed to offer a superior product with an extra benefit for the consumer," said Alessandra Zambaldi, head of foreign trade and marketing at Alpes.

The firm is one of Brazil's three largest manufacturers of PVC film, currently producing 450 metric tons per month. It is planning a 20% increase in production by mid-2021.

In response to COVID-19, the firm identified new markets for application of the product, including protection of surfaces such as debit and credit card machines, doorknobs, handrails, keyboards, and touch screens.

The product is also used to cover the skin after tattooing or cosmetic procedures. "When we identified the use of our plastic film for this purpose, we conducted tests to make sure it's hypoallergenic," Zambaldi said.

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https://phys.org/news/2020-11-plastic-foods-surfaces-inactivates-coronavirus.html

How Pfizer's and Moderna's 95% effective mRNA Covid shots work

 The COVID-19 pandemic has driven a massive allocation of resources towards producing solutions, from identifying life-saving medications, tracking how the virus spreads and ultimately to preventing infection with vaccines.

As a physician scientist, I study how the virus has evolved over the pandemic, since any changes in the virus could also change the effectiveness of current treatments. On Nov. 9, Pfizer announced preliminary trial results showing that a vaccine it developed with BioNTech was about 90 percent effective. That was followed up nine days later with final trial results and two months of safety data, indicating a 95 percent effectiveness rate.

Pfizer announced on Nov. 18 that it intends to file for emergency authorization with the U.S. Food and Drug Administration.

Meanwhile, on Nov. 16, Moderna announced preliminary results for its own vaccine, developed with the U.S. National Institutes of Health, which also indicated effectiveness of about 95 percent.

This is good news, but we need to understand what it means so life can ultimately go back to normal.

DNA, messenger RNA and proteins

Both Pfizer's and Moderna's vaccines are mRNA-based. In each of our cells, DNA produces messenger RNA (mRNA) containing the templates for making proteins. It's called messenger RNA because it carries that information to other parts of the cell, where the instructions are read and followed to produce specific proteins.

When a patient is injected with mRNA in a vaccine, their cells use the information in that mRNA to create a protein: in this case, a version of the spike protein from the coronavirus that causes COVID-19. The immune system recognizes that protein as a signal to produce antibodies and immune cells.

An mRNA vaccine has some advantages for mass vaccination. It can produce robust immunity, can be made rapidly at low cost, and, like inactivated and subunit vaccines, it is impossible for it to cause someone to develop the illness.

Building immunity

This vaccine has the potential to protect many people from this devastating virus. When it is said that a vaccine is 90 percent effective, this means that if 100 people received the vaccine and were then exposed to the virus, 90 would be unlikely to get sick. While 10 would be at risk of still developing the infection, fortunately protection from vaccines is not all-or-nothing. These 10 individuals could have milder disease than someone who did not receive the vaccine.

It takes time for immune systems to prepare to fight infections. Think of building immunity to SARS-CoV-2, the virus that causes COVID-19, like preparing to run a marathon. First, the runner must register, just as the immune system must be exposed to the infectious agent. Then, they need to build stamina. For the immune system, this means making antibodies and immune cells. Finally, they run the marathon: the bolstered immune system now removes the infectious agent from the body, or prevents it from doing further damage.

In both the Pfizer and Moderna clinical trials, subjects received the vaccine in two doses, three or four weeks apart, respectively. That's about how much time it takes for the stimulated immune system to produce meaningful protection. A booster vaccine was given to produce even more antibodies and immune cells. In terms of the marathon example, this is like doing a practice marathon around three weeks into training. The runner will do better than they would have on day one, but more training is likely still needed. The booster vaccine provides that extra training.

The beginning of the end

Should we expect the pandemic to be over once a vaccine is available for public use? Not exactly. A vaccine will not be perfect, and it takes time for the immune system to be ready to protect us.

In addition, it is possible that the vaccines will be less effective than cited. Clinical trials are carefully set up, but it is possible that the virus will have evolved enough since the vaccines were designed so they will provide less benefit. It will also take time for enough vaccine to be made and administered for the population to achieve herd immunity.

Masks and social distancing will still most likely be necessary throughout 2021 because it takes time to accomplish such large-scale projects. We cannot expect herd immunity from our neighbors getting sick to get the world back to normal, even while neighbors are receiving vaccines. The human cost is unacceptable and the virus is too infectious for this to produce meaningful results unless 67 percent of the population is infected, with a lot of people dying up to that point and afterwards.

We are in a scary time but have reason to have hope. The news of the Pfizer and Moderna vaccines is good news and could potentially bring the world back to something more normal. We must not forget that it will take time and all of us working together. Masks and social distancing are our reality right now, and will remain so until at least next year. We must persevere with these measures, even when we find them frustrating. There is a light at the end of the tunnel and we can all reach it if we work together.

https://medicalxpress.com/news/2020-11-covid-vaccines-pfizer-moderna-effective.html

Anti-COVID-19 nasal spray 'ready for use in humans'

 A nasal spray that can provide effective protection against the COVID-19 virus has been developed by researchers at the University of Birmingham, using materials already cleared for use in humans.

A team in the university's Healthcare Technologies Institute formulated the spray using compounds already widely approved by regulatory bodies in the UK, Europe and the US. The materials are already widely used in medical devices, medicines and even food products.

This means that the normal complex procedures to take a new product to market are greatly simplified, so the spray could be commercially available very quickly.

A pre-print (not yet peer-reviewed) study describes cell culture experiments designed to test the ability of the solution to inhibit infection. They found cell-virus cultures inhibited the infection up to 48 hours after being treated with the solution and when diluted many times.

The spray is composed of two polysaccharide polymers. The first, an antiviral agent called carrageenan, is commonly used in foods as a thickening agent, while the second a solution called gellan, was selected for its ability to stick to cells inside the nose.

The gellan, is an important component because it has the ability to be sprayed into fine droplets inside the nasal cavity, where it can cover the surface evenly, and stay at the delivery site, rather than sliding downwards and out of the nose.

Lead author on the paper, Dr. Richard Moakes, said: "This spray is made from readily available products that are already being used in food products and medicines and we purposely built these conditions into our design process. It means that, with the right partners, we could start mass production within weeks."

The spray works in two primary ways. Firstly, it catches and coats the virus inside the nose, from where it can be eliminated via the usual routes—either nose-blowing or swallowing. Secondly, because the virus is encapsulated in the spray's viscous coating, it is prevented from being uptaken by the body. That means it will reduce the viral load in the body, but also even if virus particles are passed on to another person via a sneeze or cough, that person is less likely to be infected by active virus particles.

Co-author Professor Liam Grover, says: "Although our noses filter thousands of liters of air each day, there is not much protection from infection, and most airborne viruses are transmitted via the nasal passage. The spray we have formulated delivers that protection but can also prevent the virus being passed from person to person."

The team believe the spray could be particularly useful in areas where crowding is less avoidable, such as airplanes or classrooms. Regular application of the spray could significantly reduce disease transmission.

"Products like these don't replace existing measures such as mask wearing and handwashing, which will continue to be vital to preventing the spread of the virus," adds Dr. Moakes. "What this spray will do, however, is add a second layer of protection to prevent and slow virus transmission."

More information: Richard J. A. Moakes et al. Formulation of a composite nasal spray enabling enhanced surface coverage and prophylaxis of SARS-COV-2, (2020). DOI: 10.1101/2020.11.18.388645

https://medicalxpress.com/news/2020-11-anti-covid-nasal-ready-humans.html

Weill Cornell Researchers ID Specific Lung Changes in COVID-19

 Researchers at Weill Cornell Medicine identified a specific and unique kind of immune cell activity in the lungs of COVID-19 patients. This activity, they found, is different from the type of immune cell activity found in other respiratory infections.

They leveraged Fluidigm Corporation’s Imaging Mass Cytometry (IMC™) on the company’s Hyperion Imaging System™ to conduct spatial analysis of lung tissue at the single-cell level throughout a broad range of the disease. The data is currently available on the medRxiv pre-print service, and had not been peer-reviewed.

The data suggests that infiltration of neutrophils, a specific type of immune cells, increased in acute respiratory distress syndrome (ARDS) and early COVID-19 compared to normal lungs, but this is known to be more of a sign of bacterial pneumonia. More inflammation, infiltration of interstitial macrophages—another type of immune cell—and complement activation, a part of the innate immune system, as well as fibrosis (scarring) was typically found in COVID-19.

They also found that although late COVID-19 disease shows signs of tissue healing, the high mortality rate suggests damage to the lungs caused by complement activation with other immunological activities that can cause abnormal blood clotting in the lungs. In contrast, the study found that the hyperinflammatory activity as evaluated by cytokine levels in the peripheral blood is specific to COVID-19.

The researchers believe that early interventions that decrease off-target immune responses or that activate the complement cascade might improve outcomes for COVID-19 patients.

The investigators leveraged high parameter imaging mass cytometry to target the expression of 36 proteins in order to investigate the cellular composition and spatial architecture of human acute lung injury including COVID-19 at the single cell level. The authors wrote, “This spatially resolved single-cell data allowed us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint.”

“Understanding the pathology of COVID-19 lung disease is essential for developing interventions and treatment regimens that can improve patient outcomes and reduce mortality,” said Chris Linthwaite, president and chief executive officer of Fluidigm. “This study adds to a growing body of data underscoring the importance of tissue architecture and three-dimensional cell-to-cell interactions in critical biologic and pathophysiologic process.”

Olivier Elemento, director of the Englander Institute for Precision Medicine and Cornell University Professor of Physiology and Biophysics team, said, “The unique spatial aspects of Imaging Mass Cytometry enabled us to view not only the structure of the tissue but also the interplay between infected cells and the immune system in COVID-19 patients. The diverse range of tissue samples offered incredible insight into the mechanisms of disease progression in these patients, and the rich dataset provided our computational biologists with an opportunity to interpret changes in tissue architecture as well as detect and understand patterns that may provide insights into future approaches to therapies.”

Additional findings from the study demonstrated a significant decrease in alveolar lacunar space, increased immune infiltration, and apoptosis-mediated cell death. The authors wrote, “We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyper-inflammatory cell state associated with lung damage. By leveraging the temporal range of COVID-19 severe fatal disease in relation to the time of symptom onset, we observe increased macrophage extravasation, mesenchymal cells, and fibroblasts abundance concomitant with increased proximity between these cell types as the disease progresses, possibly as an attempt to repair the damaged lung tissue.”

Which is to say, macrophages, a specific type of immune cell, moved from the circulatory system into the lung tissue. Macrophages respond to bacteria and other invasive pathogens, but they also present antigens to T cells and initiate inflammation by releasing cytokines. Other types of cells, such as mesenchymal cells and fibroblasts, which, in particular are involved in wound healing, were also observed.

Linthwaite noted, “Our robust IMC platform is uniquely suited to exploring these interactions with single-cell resolution. Significantly, in this study, IMC analyses uncovered novel interactions and cellular phenotypes that add important new insights into mechanisms of COVID-19 pathology, and these insights may help drive clinical practices that can improve patient outcomes.”

https://www.biospace.com/article/weill-cornell-researchers-id-specific-lung-changes-in-covid-19/

FDA Grants EUA to Olumiant-Remdesivir Combo for Hospitalized COVID-19 Patients

 The U.S. Food and Drug Administration granted Emergency Use Authorization to a combination of Eli Lilly’s and Incyte’s Olumiant (baricitinib), a rheumatoid arthritis treatment, and Gilead Sciences’ remdesivir as a treatment for hospitalized patients diagnosed with COVID-19 who require supplemental oxygen or ventilation.

The FDA granted EUA to the treatment based on clinical data that showed baricitinib, in combination with remdesivir reduced time to recovery within 29 days following treatment compared to remdesivir alone. The safety and effectiveness of this investigational therapy for use in the treatment of COVID-19 continues to be evaluated, the FDA said. Specifically, the EUA was authorized for patients two years of age and up with “suspected or laboratory confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).” Olumiant has not been approved by the FDA to treat COVID-19, and the efficacy, safety and optimal duration of treatment of baricitinib for COVID-19 have not been established. Remdesivir was granted EUA in May. This is the first combination regimen for COVID-19 authorized by FDA.

For Eli Lilly, the EUA marks the second asset given the green light as a treatment option for the novel coronavirus. Earlier this month, Indianapolis-based Eli Lilly and partner AbCellera won EUA for the investigational neutralizing antibody bamlanivimab (LY-CoV555). Bamlanivimab is a neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, which should neutralize the virus, and potentially prevent and treat COVID-19. Bamlanivimab is derived from the blood of a recovered patient and was first discovered by AbCellera from the blood of one of the first recovered COVID-19 patients in the United States.

Eli Lilly Chief Executive Officer David Ricks said the EUA for Olumiant and remdesivir is an important milestone for hospitalized patients on oxygen. He said the addition of baricitinib may help speed the recovery of patients.

Olumiant is a once-daily, oral JAK inhibitor approved in the U.S. for the treatment of adults with moderately to severely active rheumatoid arthritis. It’s thought that inhibition of JAK 1 and JAK 2 may also play a role in reducing the cytokine storm associated with the most severe complications of COVID-19. In addition, Eli Lilly suspects Olumiant may have a role in inhibiting the host cell proteins that assist in viral reproduction, reducing the ability of infected cells to make more of the virus.

Data from the ACTT-2 study showed patients treated with the combination improved their median time to recovery from eight to seven days compared to remdesivir alone, a 12.5% improvement. The one-day reduction was considered statistically significant, Eli Lilly said when it announced the results. Also, the data showed the proportion of patients who progressed to ventilation, or died by Day 29, was 23% lower in the combination arm compared to remdesivir alone. Death by day 29 for these patients was reduced by 35% for the combination treatment compared to the Gilead drug alone.

The study also met a key secondary endpoint comparing patient outcomes at Day 15 using an ordinal 8-point scale ranging from fully recovered to death.

Incyte CEO Hervé Hoppenot said the company is pleased the FDA authorized the EUA to the combination treatment. He said the company is working toward other treatments for the global pandemic which had infected more than 56 million people across the globe and more than 11 million in the United States. There have been 1,356,952 people who have died from the disease, including 251,970 in the U.S.

https://www.biospace.com/article/fda-grants-eua-to-combination-of-olumiant-and-remdesivir-in-hospitalized-covid-19-patients/