Beating COVID Is Child's Play

 In a recent video, Betsy Herold, MD, chief of the Division of Pediatric Infectious Disease at the Children's Hospital at Montefiore and Albert Einstein College of Medicine in New York City, discusses new research on why children experience less severe COVID-19 infections and how it could lead to innovative therapeutics for infection moving forward.

The following is a transcript of her remarks:

We began looking at COVID-19 back in March of 2020, when it first really became apparent this was going to be a significant problem. At that time, mostly we were focused obviously in our own region -- so in the Bronx and in New York in general. One of the first observations we made was that the disease seemed to be causing more severity in adults compared to children.

So in collaboration with colleagues here at Montefiore and Albert Einstein College of Medicine, as well as colleagues at Yale University, we began to collect samples from both adults and children who were being hospitalized with COVID to answer the question: What was different in the way children were responding to COVID compared to adults, and could we then learn from that to, perhaps in the future, help patients who are developing disease?

So we've completed and published two studies and are working on some additional ones right now. In those first studies, what we found is when you looked at the blood in the patients who were adults versus those who were children -- and we divided them essentially also based on the disease presentation -- so when we look at those three groups, the kids who do well, the adults who do well, and the adults who do poorly, there are clear differences.

The children overall had lower levels of what are called inflammatory cytokines. These are proteins that are secreted typically by immune cells, but they can be secreted by other cells in your body that cause inflammation. Now that by itself was not surprising. We already knew that clinically, that adults who were doing poorly were going to have higher levels of those proteins compared to adults who did well and compared to children.

But there were two proteins that really caught our eye and they became very interesting. And those are called IL [interleukin]-17A and interferon gamma. Now, the reason they were interesting is -- it was the opposite -- they were higher in the children compared to the adults -- compared both to the adults who did well and the adults who did poorly. So that suggested that perhaps those proteins were being protective.

Now, there are many cells that can make these proteins, but to simplify the story, let's just say that typically we think of them as being made by your T cells, which is part of your adaptive immune response. But when we collected T cells from a subset of patients, the T-cell responses to COVID – which, if that was the source of these "good guy" proteins, we'll call them – would've been higher in the children. It actually was the opposite: they were higher in the adults.

So clearly that was not the source of those proteins that looked like they potentially were being protective. The other place that those proteins can come from is something called your innate immune system. Your innate immune system is really the first part of your immune system.

The first time any of us see a pathogen that we've never seen before, we all sort of have this immediate response in our body of an innate immune response -- that can be proteins and cells that respond without having any memory of it [the pathogen]. That usually helps us in the first few days of infection.

Then our body starts to make what we call the adaptive immune response, which is specific for each different pathogen that we look at. And that includes your antibodies and your T cells. So since that interferon gamma and that IL-17A was not coming from the T cells, we thought those proteins are also made by innate cells, and maybe that's where it's coming from.

What that suggested to us was a model in which if you make a good enough innate response, then you maybe don't need to make as much of that adaptive memory response, because you've gotten rid of the virus. The model that our data suggests, and has subsequently been validated by other groups as well looking at different patient populations, is that kids make a better initial innate adaptive response, which helps them, number one, recover from the virus more quickly, but number two, leads to them not needing to make quite as much of that adaptive response.

And some of that adaptive response actually is what's contributing to the disease. When you have an "over-vigorous" – is the way I like to put it – adaptive response, too many T cells activated, maybe some of the antibodies in the process of trying to kill the infected cells can actually lead to more inflammation. And that leads to that ARDS [acute respiratory distress syndrome] kind of syndrome that we see in association with COVID.

So how do we use this knowledge to prevent or to treat infections as we move forward in the future? One concept there is to actually use the proteins that we and others have identified, some of these innate molecules, and actually administer those. And there have been a few clinical trials to look at giving interferon, for example, which is one of those families of proteins, to patients who have COVID. So far, that data has not been a home run yet.

But another way to think about this, and some people call this "trained immunity," is to think why would children have a stronger innate immune response? One theory is that every time you have a viral infection, your innate response sort of gets turned on. And so maybe because children have more frequent viral infections, just your run-of-the-mill colds, their innate system is a little bit more turned on and it's ready to go. There is some data in animal models that suggested that indeed is the case.

So some people have argued that vaccinations -- not even just specific COVID vaccines, but that in general sort of mucosal vaccines, or other ways of turning on your innate immune system -- might work to protect people against infections.

So I think this is a really important area of research. We don't have all the answers quite yet.

https://www.medpagetoday.com/infectiousdisease/covid19/97496

How Can the U.S. Preserve Its Medical Supply Chain?

 Onshoring medical manufacturing is part of a strategy to shore up the nation's medical supply chain, but it can't be the entire strategy, according to a new report from the National Academies of Sciences, Engineering, and Medicine (NASEM).

"If you are thinking about onshoring the entire global supply chain, that would be a daunting logistical task, and associated with a huge price tag as well," said Ozlem Ergun, PhD, professor of mechanical and industrial engineering at Northeastern University in Boston. "Onshoring can be part of a cost-effective strategy for increasing resiliency of our medical product supply chains -- however, it should be treated as part of a resiliency strategy, but not the one [and only] solution."

That is because supply chain shortages can arise in a number of ways, ranging from public health emergencies to reduced production or transportation capacity to failures in coordination.

"All sorts of resilience strategies, including onshoring, should be evaluated through a framework, so that we can end up with coming up with the best strategy for a given set of products that is cost effective and most impactful," said Ergun, a member of NASEM's Committee on Security of America's Medical Product Supply Chain, at an online event Thursday announcing the report's release.

Among the committee's recommendations is that the FDA make sourcing, quality, volume, and capacity information publicly available for all medical products approved or cleared for sale in the U.S. This is going to require that drug manufacturers and device makers publicly disclose their manufacturing locations and other data, explained committee member Erin Fox, PharmD, senior pharmacy director at the University of Utah, Salt Lake City.

A public database with this information can be used "in part to just better understand the vulnerabilities of where we can target the resources to shore up the most vulnerable parts of our supply chain," Fox said. The data also can be used to predict potential medication shortages, and "we can also involve third-party companies who can help with rating scales and other rating systems for rating quality that can then be used by purchasers."

"And of course, all of this truly hinges on Congress making the changes and the necessary amendments to permit the public disclosure of this information," she said.

Equipped with supply data, health systems would be able to do their part by deliberately incorporating quality and reliability -- in addition to price -- in their contracting, purchasing, and inventory decisions.

Whether they're a large system contracting on their own or part of a group purchasing organization making contracts for large numbers of hospitals across the country, "make sure to award contracts to suppliers that have superior quality and reliability, and award multiple contracts versus single-source contracts for that diversification and more reliability," Fox said. "This marketplace reward can hopefully drive companies to choose to improve their supply chains."

According to the NASEM report, FDA also needs to work with the Assistant Secretary for Preparedness and Response (ASPR) to cultivate "capacity buffering" for critical medical products as protection against long-lasting supply disruptions or demand surges.

For example, the agencies could do an "analysis of what 'crisis price lists' might look like for the supply chain of critical medical products," said committee member W. Craig Vanderwagen, MD, a manager at East West Protection and former ASPR under President George W. Bush.

"ASPR could develop and manage a database of that kind of information ... [and] FDA and ASPR should fund research and development in advanced pharmaceutical manufacturing techniques," which might help with onshoring of certain parts of the manufacturing process, he suggested.

"It begins with awareness, transparency, and the database," Vanderwagen concluded. "Without data and evidence, it's almost impossible to rationally approach the notion of how we're going to mitigate, prepare, and respond to" shortages.

The NASEM group also recommended that the ASPR develop strategies to respond to medical product shortages at the national and regional levels. This would include strategies for modernizing inventory stockpiling management for the Strategic National Stockpile and beyond, according to the committee.

Ultimately, major exporters of medical products, including the U.S., should negotiate a plurilateral treaty under the World Trade Organization that prohibits export bans and restrictions on medical product supply chains. Any country that violates the terms of this agreement should be subject to sanctions by other signatories of the agreement, explained committee member Lee Branstetter, PhD, professor of economics and public policy at Carnegie Mellon University in Pittsburgh.

"We think that a trade agreement like this is likely to be self-enforcing," he said. "Any country that seeks to restrict export of key products or components out of its borders, is likely to find itself quite vulnerable to the reaction by its trading partners to restrict its access to key products or components that it does not itself produce."

https://www.medpagetoday.com/publichealthpolicy/healthpolicy/97524

China to handle COVID clusters in a targeted, science-based manner

 China will cope with local COVID-19 outbreaks in a “science-based, targeted” manner to maintain the normal order of life, according to a government work report released at the open of the country’s annual meeting of parliament on Saturday.

China will stick to preventing inbound COVID infections and the domestic resurgence of the disease while continuing to refine its epidemic measures, according to the report.

The country will also step up research into coronavirus variants and their prevention and accelerate researching and developing vaccines and effective medicines against COVID, the report said.

In a separate document issued on Saturday, China’s state planner the National Development and Reform Commission (NDRC) said the country will organise research into COVID vaccination using products based on different technologies and increase the coverage of COVID boosters.

China will further speed up the domestic research, development and approval of COVID-19 medicines in accordance with epidemic control needs, and coordinate efforts on production, storage and quality supervision.

China will also enhance cross-border trade to ensure the unimpeded trade of vaccines and materials needed to produce them, the NDRC said in the document.

https://kfgo.com/2022/03/04/china-to-handle-covid-clusters-in-a-targeted-science-based-manner/

Dems frustrated with latest Manchin pitch on Build Back Better

 Senate Democrats are feeling exasperated with Sen. Joe Manchin’s (D-W.Va.) latest proposal on a scaled-down version of President Biden’s Build Back Better agenda that would leave out big social spending initiatives like expanded child care, universal pre-kindergarten, national paid family leave and long-term home health care.   

Manchin is proposing that his colleagues choose one 10-year program to focus on and devote the other half of revenues raised from tax reform and prescription drug reform to deficit reduction and fighting inflation.

He is suggesting limiting new spending to climate programs instead of an array of social spending initiatives that he says would likely get baked into the federal budget baseline for years to come.

Manchin says the country has to “get its fiscal house in order” before embarking on new grand spending plans, but his colleagues aren’t ready to let go of big, ambitious reforms they’ve talked about for more than a year, such as direct federal support for expanded access to child care.   

He argues that the nation can’t keep adding to the deficit when inflation is running at a 40-year high. But that stance is fueling tension with leading Democratic progressives and liberal advocacy groups. 

“If he wants to focus on an economic package, then he needs to remember child care is an economic issue,” said Sen. Elizabeth Warren (D-Mass.) when asked about Manchin’s pared-down proposal.  

“We have many, many, many parents at home today because they cannot get child care. We have people who can’t work in the child care industry because they don’t make a living wage,” she added. “If we want to have an economy that’s firing on all cylinders, we want people to be able to go back to work.”

“Let me point out, that affects inflation. When you don’t have enough workers, then prices go up,” she argued in response to Manchin’s concern about rising prices, which he has cited as a major reason not to pass Biden’s Build Back Better agenda.  

Senate Health Committee Chairwoman Patty Murray (D-Wash.), who is leading the effort to pass funding for expanded access to child care and universal pre-kindergarten, said her priorities “are all part of dealing with inflation.”   

“We all understand that and we’re all fighting for it,” she said.  

“What I feel very strongly is that Congress needs to address some of the costs that families are feeling today. Child care is a huge part of that and it is a barrier for people to be able to go back to work so they can support their families in this challenging time,” she said.  

Manchin, however, has raised doubt about the argument that spending hundreds of billions of dollars on new social programs will fight inflation by lowering costs.  

“I’ve never found out that you can lower costs by spending more,” he told reporters after Biden’s first State of the Union address Tuesday evening.

And he shrugged off Biden’s efforts Tuesday to revive the key elements of his Build Back Better agenda, such as spending hundreds of billions of dollars to reduce child care costs and establish universal pre-kindergarten. 

“It just keeps adding up and up,” he told reporters. “To me, it’s all about inflation.” 

“Inflation is the No. 1 enemy we have in America today,” he said.   

Some Democrats say they are growing tired of the back-and-forth with Manchin, which has dragged on for months, leaving them deeply frustrated over their inability to strike a deal.  

One lawmaker said, “We’re all so tired of BBB.”  

https://thehill.com/homenews/senate/596822-democrats-frustrated-with-latest-manchin-pitch-on-build-back-better

TX judge rules Biden admin can't exempt migrant minors from Trump-era order

 A Texas judge on Friday ruled that the Biden administration cannot exempt unaccompanied migrant children from a Trump-era order, a decision that could lead U.S. Border Patrol to turn children away. 

During the early part of the pandemic, former President Trump launched Title 42, a controversial public health policy that would allow the U.S. to immediately expel migrants who came to the border. The Biden administration has continued to operate under that order, but carved out an exception from unaccompanied migrant children.

However, Texas District Court Judge Mark Pittman, a Trump appointee, ruled against the Title 42 exemption, according to CBS News. 

Pittman said that the Biden administration did not thoroughly justify the Centers for Disease Control and Prevention orders that codified the exclusion of unaccompanied minors from Title 42, calling them "arbitrary and capricious," CBS reported.

Pittman also argued that Texas had been financially hit as a result of the exemptions due to education and medical costs for the migrant children now living in the state. 

The ruling comes hours after a Washington, D.C., judge ruled against the Biden administration from using Title 42 to expel migrants back to countries where they may face persecution.

The decision on Friday marks the latest instance in which Texas has successfully blocked Biden administration immigration initiatives.

A judge in the state blocked a 100-day moratorium on deportations in February, and the Supreme Court sided with the state in August in a battle to reimplement what is formally known as the Migrant Protection Protocols, one of the most controversial Trump-era immigration programs.

The Biden administration has expelled hundreds of thousands of migrants under Title 42, which they have argued is necessary for public health purposes. However, the administration has been against using the policy to expel unaccompanied children, choosing instead to transfer them to shelters run by the Department of Health and Human Services.

It's unknown whether the Biden administration will start expelling unaccompanied children at the border in light of Pittman's ruling. Around 16,000 minors were expelled under the policy during the Trump administration before a judge blocked the policy in November 2020, according to CBS. 

https://thehill.com/policy/national-security/596977-texas-judge-rules-biden-administration-cant-exempt-migrant-children

WNBA's Brittney Griner in Russian custody: report

 Russian officials have detained WNBA start Brittney Griner at an airport for after they allegedly found hashish oil among her possessions, according to a report from The New York Times.

Griner, a seven-time WNBA all-star who plays for the Phoenix Mercury, was detained by the Russian Federal Customs Service for possession of vape cartridges containing the oil at Sheremetyevo airport, according to the paper. 

The Customs Service said that its officials had detained a U.S. player who had won two Olympic gold medals, but did not release her name. Griner competed for the U.S. Women's Basketball team in 2016 and 2021. 

Russian news agency TASS later reported that it was Griner after confirmation from law enforcement. 

The Customs Service said in its statement that it had opened a criminal case into the transportation of drugs and that the player had been detained amid an investigation.

Transportation of drugs in Russia can result in a sentence of up to 10 years in prison.

Griner, like many other WNBA players compete in Russia during the off season where they can often obtain more lucrative contracts. Griner has played for UMMC Ekaterinburg for several years, according to the Times. 

Many players began to leave Russia following Russian President Vladimir Putin's announcement that the country's military would invade Ukraine.

The WNBA previously confirmed that it was “in contact with WNBA players who are in Russia, either directly or through their agents.”

The Russia-Ukraine conflict has shaken the sports world as Russian athletes in several sports have called for peace with Ukraine. 

Washington Capitals forward Alexander Ovechkin called for "no more war" with Ukraine following a practice in February. 

"Please, no more war. It doesn't matter who is in the war — Russia, Ukraine, different countries — we have to live in peace," he said at the time. 

The Hill has reached out to the WNBA, Mercury and the U.S. State Department for comment. 

https://thehill.com/policy/international/russia/596996-wnbas-brittney-griner-in-russian-custody-report

LTC small homes could become big venture, but policy, funding must catch up

 While skilled nursing construction in many parts of the country has been stagnant over the last few years, one Arkansas operator has found a development strategy that attracts both lenders and residents.

Not only did census increase at Southern Administrative Services’ Green House communities during the pandemic; managing member John Ponthie carried on with a multi-year building plan that will bring two more cottages online in the weeks ahead.

Small-house living and private room concepts were bolstered by COVID-era research that showed they reduced the risk of infection and deaths. In February, the chorus calling for better support for operators in pursuit of infrastructure changes and alternative models of care grew again.

First, Harvard Medical School’s David Grabowski, Ph.D., well-known long-term care expert, and research colleague Brian McGarry, Ph.D., assistant professor of medicine at the University of Rochester, included alternative models of care in a list of 10 key strategies that could transform the skilled nursing sector. 

“It is now clear that the congregate, hospital-like approach to caring for disabled older adults is not only inconsistent with residents’ preferences, it also may directly contribute to the spread of deadly infections and diseases,” Grabowski and McGarry wrote in a special issue of the Annals of the American Academy of Political and Social Science. “Nursing homes need new models. … Policy-makers should encourage the development of more small home, resident-centered models.”

That was followed a few days later by the announcement of the Biden administration’s new vision for nursing homes, which includes a focus on transitioning away from shared units toward private rooms.

For those who already work in the space, the idea that policy could soon begin to encourage alternative nursing home models was embraced as a “thrilling” development. The Green House Project is encouraging the administration to make private rooms a requirement of participation in Medicare and Medicaid, removing any financial incentive to maintain them.

But others have long said such alternatives work much better in theory than on the ground, citing obstacles such as low operating margins, construction and financing costs and regulatory roadblocks.

Susan Ryan, Green House Project’s senior director, pushes back against the idea that small homes aren’t financially viable. She points to operators like Ponthie who save money using smart design and less-opulent but still home-like settings. Still, she and other Green House devotees say a key piece of advancing alternative models will be cost-offsets.

“If there’s different financing and reimbursement that allows providers to invest in their homes and encourages them to do so, then I think you would see more providers start to gravitate toward Green House,” said Adam Berman, president and CEO of Massachusetts-based Legacy Lifecare. “I think that’s the No. 1 thing that needs to be solved for.”

Voting with their feet

While Green House is not the only small-house nursing home model in the U.S., its trademarked model makes it the easiest to track. The Green House Project says its homes are now in 32 states, with 83 organizations operating campuses that include 371 individual small homes.

They feature cottages of 10 to 12 residents who have private suites, share decentralized kitchens and common areas, and are cared for by CNAs trained as universal workers using a person-directed care approach.

Small house living started in rural areas, where developers could acquire, relatively inexpensively, existing nursing homes or acreage required to support multiple buildings. In many ways, it remains the province of rural and non-profit operators.

For-profit Southern Administrative operates five Green House campuses in Arkansas, along with about two dozen traditional facilities. A sixth Green House is scheduled to open in the next two weeks, with a seventh slated for Bentonville, AR. 

“Since I’ve found Green House, I’ve done exclusively Green House. It’s the right, best model,” Ponthie said. “I can’t build it fast enough.”

Peers questioned his plans to put his second Green House campus in Rison, AR, population 1,350, a rural area with little wealth and few Medicare-backed rehab admissions. During COVID, demand pushed Southern Administrative Services to add a seventh cottage to that campus.

“People vote with their feet,” Ponthie said, adding that traditional rural providers are facing unprecedented closures. “During COVID, we grew our census. Everyone else had huge declines. Drop the mic. We’re done. The demand is there.” 

A private room and suite inside the Green House Cottages of Poplar Grove, in Little Rock, AR.

Keeping beds full, and providing a workplace that discourages staff turnover, are key to the Green House model, both operationally and financially. The Green House Project reports a 29% turnover rate for CNAs, compared to the 129% found in a national Health Affairs study.

Reducing turnover — and limiting the need for ancillary staff such as housekeeping and dining services — is one of the ways Ponthie says he keeps his daily costs in check.

“The cost differential operationally between my Green House and my traditional homes is not much, less than 10%, maybe 5 to 8,” he said. “What you get for that is exponentially greater.”

One internal Green House study found costs of care could actually be lower, with Green Houses spending an average $261 per patient per day compared to the national average of $271 at traditional facilities.

Financing hurdles remain

Because he had a track record in the industry, Ponthie was able to secure private financing for each of his Green House projects. But he said some have struggled to get low-interest loans through HUD, making financing a major obstacle.

He recommended the federal government establish a lending program for construction of alternative models, provide incentive grants or pay higher differentials for private-bed care. Or the federal government could use civil monetary penalties and redistribute them to providers using alternative models.

“They’ve got untold ways they could do it,” Ponthie said.

Another option on the table: a $1.3 billion pilot program included in the stalled Nursing Home Accountability and Improvement Act. It would provide up to $39 million per facility to implement person-centered design features and workforce strategies.

Grabowski and McGarry said states also should get in the game, arguing that higher Medicaid payments would “encourage greater competition between facilities for new long-stay residents, leading to greater investments in private rooms, a more home-like setting, and high-quality staff.”

Finding ways to flourish 

Ryan said operators should be mindful of creating a property that can attract a wide payer mix. Some have found success in designating certain cottages for rehab, memory care or even patients requiring ventilators.

For now, many nonprofit organizations offset their development costs by fundraising to cover large portions of the construction cost or using municipal bonds. Legacy raised most of its own capital when constructing its original Green House, the first in an urban setting, in 2010. 

They faced another factor that has dampened interest in alternative models: certificate of need laws or nursing home moratoriums. To build, operators in many states need to acquire a license by buying an existing facility — adding millions of dollars — before renovations to private rooms even begin.

Legacy worked with legislators who were intrigued by the Green House concept; a bill later passed, clearing the way for a 10-story, 100-resident building in Chelsea, MA. The organization continues to bring elements of the Green House approach to its other five campuses, converting to private beds where possible.

Ryan hopes all the current attention will encourage others to take the first steps, anticipating that more support could be close on the horizon.

“If government will step up and say, ‘Yes, we can, and here are some of the incentives we’re going to provide,’ and the providers will step up and say ‘Our good enough wasn’t good enough’ … I think we can make achievable change and really make a lasting impact,” she said.

https://www.mcknights.com/news/ltc-small-homes-could-become-big-venture/