A new study led by scientists at La Jolla Institute for Immunology (LJI) suggests that T cells try to fight SARS-CoV-2 by targeting a broad range of sites on the virus—beyond the key sites on the virus's spike protein. By attacking the virus from many angles, the body has the tools to potentially recognize different SARS-CoV-2 variants.
The new research, published January 27, 2021 inCell Report Medicine, is the most detailed analysis so far of which proteins on SARS-CoV-2 stimulate the strongest responses from theimmune system's "helper" CD4+ T cells and "killer" CD8+ T cells.
"We are now armed with the knowledge of which parts of the virus are recognized by the immune system," says LJI Professor Alessandro Sette, Dr. Biol. Sci., who co-led the new study with LJI Instructor Alba Grifoni, Ph.D.
Sette and Grifoni have led research into immune responses to the virus since the beginning of the pandemic. Their previous studies, co-led by members of the LJI Coronavirus Task Force, shows that people can have a wide range of responses to the virus—some people have strong immune responses and do well. Others have disjointed immune responses and are more likely to end up in the hospital.
As COVID-19 vaccines reach more people, LJI scientists are keeping an eye on how different people build immunity to SARS-CoV-2. They are also studying how T cells could combat different variants of SARS-CoV-2. This work takes advantage of the lab's expertise in predicting and studying T cell responses to viruses such as dengue and Zika.
"This is even more important with COVID-19 because it is a global pandemic, so we need to account for immune responses in different populations," says Grifoni.
The immune system is very flexible. By re-scrambling genetic material, it can make T cells that respond to a huge range of targets, or epitopes, on a pathogen. Some T cell responses will be stronger against some epitopes than others. Researchers call the targets that prompt a strong immune cells response "immunodominant."
For the new study, the researchers examined T cells from 100 people who had recovered from SARS-CoV-2 infection. They then took a close look at the genetic sequence of the virus to separate the potential epitopes from the epitopes that these T cells would actually recognize.
Their analysis revealed that not all parts of the virus induce the same strong immune response in everyone. In fact, T cells can recognize dozens of epitopes on SARS-CoV-2, and these immunodominant sites also change from person to person. On average, each study participant had the ability to recognize about 17 CD8+ T cells epitopes and 19 CD4+ T cell epitopes.
This broad immune system response serves a few purposes. The new study shows that while the immune system often mounts a strong response against a particular site on the virus's "spike" protein called the receptor binding domain, this region is actually not as good at inducing a strong response from CD4+ helper T cells.
Without a strong CD4+ T cell response, however, people may be slow to mount the kind of neutralizing immune response that quickly wipes out the virus. Luckily, the broad immune response comes in handy, and most people have immune cells that can recognize sites other than the receptor binding domain.
Among the many epitopes they uncovered, the researchers identified several additional epitopes on the SARS-CoV-2 spike protein. Grifoni says this is good news. By targeting many vulnerable sites on the spike protein, the immune system would still be able to fight infection, even if some sites on the virus change due to mutations.
"The immune response is broad enough to compensate for that," Grifoni says.
Since the announcement of the fast-spreading UK variant of SARS-CoV-2 (called SARS-CoV-2 VUI 202012/01), the researchers have compared the mutated sites on that virus to the epitopes they found. Sette notes that the mutations described in the UK variant for the spike protein affect only 8% of the epitopes recognized by CD4+ T cells in this study, while 92% of the responses is conserved.
Sette emphasized that the new study is the results of months of long hours and international collaboration between labs at LJI; the University of California, San Diego; and researcher's at Australia's Murdoch University. "This was a tremendous amount of work, and we were able to do it really fast because of our collaborations," he says.
The World Economic Forum is partnering with the Global CEO Initiative (CEOi) to form a coalition of public and private stakeholders – including pharmaceutical manufacturers, biotech companies, governments, international organizations, foundations and research agencies – to catalyse the fight against Alzheimer’s disease.
Dementia, including Alzheimer’s (a result of rapid ageing that causes dementia), is the most expensive chronic condition of the world’s growing ageing population. Dementia is the seventh leading cause of death worldwide, cost the world $1.25 trillion in 2018, and affected about 50 million people in 2019. According to the US Alzheimer’s Association, dementia is the sixth leading cause of death in the United States, and every 65 seconds, someone in the country develops the disease.
Despite many efforts from various actors and recent promising developments, the global response to the disease has not matched the scope and scale of the challenge, with no new drugs broadly to market in 15 years. Without major breakthroughs, the number of people affected will triple by 2050, to 152 million.
“Alzheimer’s disease is uniquely devastating, and there is urgent need to address the current hurdles to progress. This effort will bring together the necessary stakeholders to prioritize and resource an engaged, efficient health system and bring much-needed detection, diagnosis and treatments to those affected by the disease,” said Arnaud Bernaert, Head of Shaping the Future of Health and Health Care, World Economic Forum.
“Alzheimer’s is the biggest public health crisis of the 21st century, requiring this multi-stakeholder initiative to catalyze coordinated global action at the scope and scale of the response to AIDS, cancer and climate change,” said George Vradenburg, founder of the Global CEO Initiative on Alzheimer’s Disease and chairman and co-founder of UsAgainstAlzheimer’s.
The CEOi-WEF partnership will explore catalytic actions in four areas: pre-clinical research to advance the understanding of the disease in global cohorts, attract more capital by lowering the risks to investment in biomarkers, develop standing clinical trial platforms, and advance healthcare system readiness in the fields of detection, diagnosis, infrastructure and access. The main focus of the year ahead is to secure commitments from policymakers and business leaders through the development of a business plan that will include key activities and metrics for the coalition’s work.
President Joe Biden in a Thursday executive order gave the Occupational Safety and Health Administration two weeks to issue revised guidance on workplace safety during the COVID-19 pandemic.
The order also directed the agency, through the secretary of labor, to reconsider whether any emergency temporary standards on COVID-19, "including with respect to masks in the workplace," are needed. If such standards are deemed necessary, OSHA should issue them by March 15, the order said.
Biden also asked that OSHA review its enforcement efforts and conduct a multilingual outreach campaign to inform workers of their rights.
It’s not clear exactly what the first guidance might entail but Biden announced in December that he would be asking OSHA to revisit its decision on emergency temporary standards, so Thursday's executive order may come as no surprise to employers.
Specifically, Biden said in that earlier announcement that he would look for the agency to target the worst violators, increase the number of inspectors and develop strategies for addressing the most dangerous workplace hazards.
OSHA has so far declined to exercise its power to implement emergency standards — an option available to the agency under certain circumstances. Employee advocates sued last year, asking a court to require the agency to take action, but the court declined, concluding that the agency was entitled to "considerable deference."
The agency instead, under the Trump administration, opted to address pandemic-related safety through guidances. These documents were flexible and sufficient, according to the U.S. Chamber of Commerce, which represents employers.
The Biden administration's first week in office included the release of a 200-page outline for fighting the COVID-19 pandemic. Among several measures, it says the administration will provide authority, through an executive order issued Thursday, to use the Defense Production Act to "fill supply shortfalls" across 12 product categories facing shortages.
The DPA is a legal tool the federal government uses to ensure suppliers prioritize its orders. It can allow the government to direct expanded manufacturing capacity at particular companies, as it did in April, when HHS announced a $489.4 million DPA contract with General Motors to manufacture 30,000 ventilators for the Strategic National Stockpile. But it's not clear how helpful this order was, as this work was taking place prior to the DPA order.
"It can be a very powerful tool," said Aron Beezley, a partner at Bradley, in reference to the DPA, though he also said it's "not the magic cure-all that some think it is."
The six vaccine candidates being developed as part of Operation Warp Speed portfolio — Moderna, AstraZeneca, Novavax, Jannsen, Sanofi and Pfizer — have priority DPA ratings. Companies manufacturing therapeutic treatments also have priority ratings. As of Dec. 31, there were 18 priority ratings issues under the DPA,according to a post by the Defense Department.
A White House spokesperson was not able to provide Supply Chain Dive with the names of companies that have received new DPA-rated orders.
The Biden administration's strategy document notes that supply chains are facing shortages of several types of personal protective equipment and supplies related to COVID-19 vaccines and testing, including N95 masks, isolation gowns, nitrile gloves, swabs, rapid test kits and others items, as well as "all the necessary equipment and material to accelerate the manufacture, delivery, and administration of COVID-19 vaccine."
The White House has not revealed the specific products or companies on which agencies will use the DPA. But "it has been invoked," Psaki said of the DPA. "So, those processes are now rapidly ongoing."
Orders move to the front of the line
"The Defense Production Act is the government's ability to direct rated orders," Beezley said, which means its orders are a priority over commercial orders. The DPA's power comes from the fact that a company can be found guilty of a crime and fined up to $10,000 if it doesn't comply with the orders given under the law, he said.
Companies that receive DPA orders from the government will usually get some sort of advanced warning that the formal directive outlining the terms is coming, Beezley said.
The DPA also provides for allocation authority, which allows the government to direct companies to reserve materials, services or facilities in anticipation of a rated order. The DPA provides legal protection to the manufacturer so other customers whose orders are held or delayed can't sue.
"Section 707 of DPA provides immunity from suits for damages so they cannot successfully sue you, so long as your failure to supply is directly connected to your DPA order," said Sarah Rathke, a partner at Squire Patton Boggs who focuses on manufacturing litigation and supply chain disputes.
The power of the DPA can also be used to expand manufacturing capacity at private companies. The federal government would provide the funds to do this, Rathke said.
"The administration could even augment private manufacturing facilities by installing federally owned equipment if required to increase drug production," three Harvard Medical School researchers wrote inan American Journal of Public Health editorialon the use of the DPA to fight drug shortages, published in September.
It can also help the government get proprietary information from companies that they might not normally be willing to share, to help the government to understand where shortages are occurring and what's causing them.
From the outside, it can be hard to tell which products would benefit from DPA the most without knowing what the specific production or supply chain issues are, Rathke said.
"That said, the whole benefit of a DPA order is you can flow it down your entire order chain, so if there are bumps, it can be applied," she said.
Suppliers are bound, too
When a company receives a rated order under the DPA, it is legally required to let the government know if it cannot comply. If it can, then it will need to pass along the order to its suppliers, which are also legally required to comply.
"If the order directs the fulfillment of an order by a certain date, and the supplier gets that order and they physically can't do it, it's not possible, then they need to immediately notify the person ... who issued that order that they can't do it by the date specified," Beezley said.
The government has said it assists in the management of this process and the coordination with suppliers.
"In order to aggressively and legally maximize the benefit of the Defense Production Act for U.S. national defense, while minimizing impact on other companies and other products, each priority rating is meticulously managed by Operation Warp Speed leaders and logistics experts, in coordination with each company and their up-stream suppliers," Operation Warp Speed Senior Counsel Gregory Gillette said in a statement last year.
When it's communicated that a supplier doesn't have enough capacity, this is where the other tools within DPA, such as the ability to provide financing for capacity expansion, can be helpful. But this also highlights the practical limits of the DPA.
"The DPA isn't a magic wand. It can't magically solve the supply chain problems that we may encounter with a vaccine," said Rathke. "People can only do what they can do."
Another limit of the law is the fact that it only works if the company is based in the United States. This could be an issue for PPE, which is often sourced from companies outside of the country with many face masks coming from China and Taiwan and gloves imported from Malaysia.
"If a company is fully outside of the United States, and they're an integral part of a supply chain that is subject to a rated order, for instance, and that company has no interest in complying, there's not much the government can do," Beezley said.
Update 645pm ET:And just like that the infamousr/WallStreetBets subreddit which destroyed countless hedge funds and even cost legendary trader Steve Cohen 10-15% in losses in January...
COHEN'S POINT72 LOSES 10-15% AMID HEDGE FUND LOSSES THIS MONTH
... has decided to go private, which means that only people who are invited can join.
Roman Health Ventures Inc, the company behind telehealth and online pharmacy business Ro, is in talks to go public through a merger with blank-check acquisition company which could value it at more than $4 billion, according to people familiar with the matter.
The sources cautioned that the talks may not lead to a deal and the company may instead opt to pursue other options such as another fundraising round. They requested anonymity to discuss the deliberations.
The name of the SPAC involved in talks with Ro could not be learned. A spokeswoman for Ro declined to comment.
A special purpose acquisition company (SPAC) is a shell company that raises funds in an initial public offering (IPO) with the aim of acquiring a private company, which then becomes public as result of the merger. For the company being acquired, the merger is an alternative to go public through a traditional IPO.
New York-based Ro last raised $200 million in July at a $1.5 billion valuation in a round led by venture fund General Catalyst.
Investor interest in telemedicine has swelled since the pandemic began as many patients in the United States booked their first virtual doctor’s appointment due to the outbreak. Investors are betting that patients will continue to use telemedicine for its convenience.
Large deals in the sector have followed. Rival Hims & Hers Health Inc agreed to go public last year through a SPAC merger.
Ro, which began as an online pharmacy that sold erectile dysfunction drugs to men, has become a full-fledged telehealth company that treats a wide range of disorders for men and women including allergies, weight loss and smoking cessation. Its online pharmacy sells over 500 generic drugs for $5 a month without insurance.
Days before Christmas, a hospital in the North Carolina foothills of the Blue Ridge Mountains maxed out its resources.
Caldwell UNC Health Care, a 137-bed hospital in Lenoir, had planned for a surge of COVID-19 cases for months. But the facility went from treating 19 infected patients to 49 in just one week, its president and CEO Laura Easton told MedPage Today. The hospital's average daily census rose from between 60 and 80 patients to between 110 and 120.
Community spread was high, and a number of employees were also out of work, Easton said. Three out of five neighboring hospitals were similarly stretched.
The outlook was bleak, but Easton and her colleagues thought of an organization nearby.
Samaritan's Purse -- an evangelical Christian charity known for treating Ebola patients and victims of war abroad -- is based in the mountain town of Boone, just 25 miles from Caldwell UNC Health Care. Easton knew the organization had previously deployed COVID field hospitals in New York City's Central Park, Italy, and the Bahamas, and thought perhaps it could do the same for them.
The chief medical officer at Caldwell UNC Health Care made a call, and it turned out the charity had been closely watching the rising number of cases in its own backyard, Easton said.
It took just a week to stand up a 30-bed field hospital adjacent to Caldwell UNC Health Care, Easton noted. Once the charity decides to deploy a field hospital, it moves fast because it knows the need is immediate and may not be the same in just a short period of time.
"This is what they do," Easton said. "They go into crisis situations, and they execute rapidly."
The field hospital at Caldwell UNC Health Care opened Jan. 7, and has been supporting that facility as well as five other hospitals in Western North Carolina. Nine days later, Samaritan's Purse also stood up a 54-bed unit in Los Angeles County, California, next to Antelope Valley Hospital.
The Lenoir, North Carolina field hospital set up on the grounds of Caldwell UNC Health Care. Photo courtesy of Samaritan's Purse.
Both non-state-run facilities -- funded by donations and staffed with volunteers, including its doctors and nurses -- are uniquely positioned to help ease the strain on hard-hit hospitals. But they haven't evaded scrutiny.
LGBTQ activists last year opposed the COVID field hospital set up by Samaritan's Purse in New York. And as the North Carolina and California facilities opened, the charity's CEO, Franklin Graham -- son of the late evangelist Billy Graham -- found himself in hot water over his support for former President Donald Trump after the Jan. 6 attack on the U.S. Capitol.
All the while, hospitals say the charity's resources have filled a void and been critical to managing a surge of COVID cases.
Field Experience
Samaritan's Purse -- founded more than 50 years ago -- has experience transporting, setting up, and running field hospitals. It has responded to natural disasters, war, and famine, with a mission of providing humanitarian aid and promoting the Gospel of Jesus Christ in doing so.
In recent years, it has increased its focus on the treatment of infectious diseases.
In 2014, Samaritan's Purse deployed staff to care for Ebola patients in West Africa, and in 2016, the organization first flew its own field hospital in response to the massive earthquake that hit Ecuador. Less than a year later, it transported a facility to treat civilians injured during the conflict between Iraqi security forces and ISIS in Mosul.
Though the pandemic presented a new challenge, it was relatively simple to adapt the charity's existing field hospital model to one with a primary focus on respiratory support, Ken Isaacs, vice president of international programs and international relations at Samaritan's Purse, told MedPage Today.
"We need to be next to a hospital ... that allows for the easy passage of patients," Isaacs said. "We're not a receiving center. We're an extension of a co-located hospital."
COVID patients who need care, such as supplemental oxygen or treatment with medications, are transferred to the field hospital to free up beds in the co-located facility, he said. Doing so eases the burden on space and staff, and allows the primary hospital to focus on caring for COVID patients who need ventilators as well as non-COVID patients with other health concerns.
Field hospitals are primarily funded through donations, Isaacs said. The cost of setting up and running the facilities ranges from about $700,000 to $3 million. Most are in operation at a site for between six weeks and three months.
Though flying portable hospitals around the world on a moment's notice is a heavy lift, Samaritan's Purse has the resources to do so.
Samaritan's Purse reported $734 million in revenue in 2019, of which ($720 million) was from contributions and grants, according to its most recently available financial filing. Total revenue was up nearly 5% from the year prior.
Expenses were $689 million in 2019, with the majority (86%) going to program services. Just shy of 8% of expenses were for fundraising, and about 5% were administrative. The organization's top paid employee was its CEO, Graham, who made $722,403 in 2019.
Charity Navigator, a nonprofit that evaluates organizations' finances and transparency, gives Samaritan's Purse its highest rating of four stars.
No Shortage of Staff
In 2019, Samaritan's Purse employed 3,305 people, and enlisted the services of 197,000 volunteers, according to its financial filing.
That is what differentiates the organization's swift ability to set up field hospitals, said Easton of Caldwell UNC Health Care.
"Their field workers are prepared to go anywhere in the world, several times a year," Easton said of Samaritan's Purse. "They had that advantage over a state government-run hospital."
The team can put out a call on Monday night, and by Tuesday afternoon feel confident that it has enough people to staff a unit, Easton said.
"These folks are very mission-motivated ... and they do this on a regular basis," she said. "When the team came in, they knew each other. They were in Italy together. They were in the Congo together. It's really a unique set of circumstances."
The state of North Carolina has been very supportive, Easton noted. However, one challenge it faces is that, if it needs to call in members of the National Guard who are medically trained, it may have to pull individuals out of the very hospitals it is intending to help.
With Samaritan's Purse, volunteers are coming from all parts of the country.
"It didn't harm the COVID effort of any one single institution like it might have if [North Carolina] pulled some of the resources that they could have within the state," Easton said.
Keith Acree, a spokesman for North Carolina Emergency Management and the Department of Public Safety, told MedPage Today in an email that the state has not set up any field hospitals during the pandemic. He said that the state does have one recently closed hospital equipped and on standby in case it is needed for overflow. However, that facility would indeed require staffing, he added.
Easing the Strain
Last year Samaritan's Purse treated more than 680 COVID patients at its field hospitals in Italy, New York City, and the Bahamas.
At Antelope Valley Hospital in California, Samaritan's Purse has already admitted 83 COVID patients to its new field hospital, according to Cynthia Frausto, director of marketing and public relations at the hospital.
Within two-and-a half days of the charity's assessment team making an initial on-site visit, the field hospital was up and running, Frausto told MedPage Today.
"We did experience the patient surge from the holidays, especially around Halloween and Thanksgiving," Frausto said. "We're in the middle of waiting to see [what] the last of the holiday patient surge is going to bring."
That's where Samaritan's Purse has been able to alleviate stress.
"They have been incredibly helpful in terms of picking up COVID patients who otherwise would have been waiting for beds in our hospital," Frausto said. "It's not only the space," she added. "The biggest help is having the staff and the resources that come with Samaritan's Purse. They provide all of their supplies, nurses, doctors, techs. They come well-equipped to help these patients and the hospital."
Easton of Caldwell UNC Health Care concurred.
Co-located hospitals provide other support, such as patient medical records, connections to oxygen tanks, pharmaceuticals, and even malpractice insurance, Easton said.
Though it is not a profitable endeavor for Caldwell UNC Health Care, billing insurers for patient care should cover the cost, she said.
Facing Opposition
Both Easton and Frausto said that their respective communities have been supportive of Samaritan's Purse setting up field hospitals.
However, that hasn't always been the case.
After Samaritan's Purse set up a 68-bed field hospital in New York City's Central Park last April, the charity's CEO and Christian minister Franklin Graham said in a statement that it had faced backlash from eight democratic members of New York's Congressional delegation, the New York City Commission on Human Rights, and the Reclaim Pride Coalition.
Their objections focused on a statement of faith the charity asks its employees to sign and its volunteers to support. The statement notes the organization's belief that marriage is between a man and a woman.
Graham said at the time that the organization didn't believe it was the time or place to wage the debate.
"It's true, for 50 years, we have asked our paid staff to subscribe to a statement of faith -- but we have never asked any of the millions of people we have served to subscribe to anything," Graham said. "In other words, as a religious charity, while we lawfully hire staff who share our Christian beliefs, we do not discriminate in who we serve."
"We have provided billions of dollars of medical care and supplies, food and water, and emergency shelter without any conditions whatsoever," he added.
New York's Mount Sinai Health System, with which Samaritan's Purse partnered on the Central Park field hospital, declined a request for comment for this story.
Though Samaritan's Purse said that its other field hospitals have not faced similar opposition, Graham has come under fire for an unrelated reason during the most recent openings.
Following the siege on the nation's Capitol Jan. 6., Graham -- a supporter of former President Donald Trump -- made public comments against a second impeachment of Trump for inciting an insurrection.
"Shame, shame on the ten Republicans who joined with @SpeakerPelosi & the House Democrats in impeaching President Trump yesterday," Graham tweeted Jan. 14. "After all that he has done for our country, you would turn your back & betray him so quickly? What was done yesterday only further divides our nation."
In response, the nonprofit Faithful America -- which describes itself as a community of Christians committed to social justice -- launched a petition calling for Graham to be removed from his leadership positions at Samaritan's Purse and the Billy Graham Evangelistic Association. It has garnered more than 25,000 signatures.
"By appearing to legitimize Franklin Graham's hateful politics and his lies about the 2020 election results -- which were part of the disinformation campaign that provoked the deadly attack on the U.S. Capitol -- the board of Samaritan's Purse is detracting from its vital medical mission and undermining its intended message of Christian love," Nathan Empsall, an Episcopal priest and campaigns director at Faithful America, said in an emailed statement.
Empsall said that enabling conspiracy theories can also lead to a fractured news environment, misinformation, and the additional spread of COVID.
"The work of Samaritan's Purse staff members can be incredibly beneficial in spite of Franklin Graham, including in COVID-19 field hospitals from Italy to North Carolina -- yet those professionals could do even more under different, reasonable leadership," he said. "How much more love and healing would Samaritan's Purse achieve if it welcomed all qualified health-care workers?" he questioned. "And how many patients have chosen to stay away in fear of receiving biased, substandard care?"
Committed to the Cause
Paul Saber, who serves on the boards of both Samaritan's Purse and the Billy Graham Evangelistic Association, provided a statement in response to the petition, saying that Faithful America fabricated a lie that Franklin Graham incited violence at the Capitol.
"Mr. Graham was not in Washington, D.C., he didn't encourage people to go to the Capitol on January 6, and he condemned the violence at the Capitol," Saber said. "The Boards of Directors for Samaritan's Purse and the Billy Graham Evangelistic Association have expressed that they fully support Franklin Graham and are more than satisfied with the job he has done and is doing in leading these ministries to bless people in over 100 countries around the world."
Isaacs of Samaritan's Purse said that, at the current stage of the pandemic, there continues to be international interest in its COVID field hospitals.
Its resources -- though substantial -- can only stretch so far.
"We consider each situation and request on a case-by-case basis," Isaacs said. "We don't want to say no, but we can't say yes everywhere either."
He said that he expects and hopes infections will continue on a downward trajectory this year, especially with vaccinations.
"I hope that we're not needed," Isaacs said. "What we have to offer is just a small thing when you look at the magnitude of the disease," he added. "But if it's a service we can provide, we want to do that."
Easton of Caldwell UNC Health Care also said that she hopes COVID cases will continue to decline.
To date, about 80 patients have been treated at the field hospital in Lenoir, she said.
That included a husband and wife who celebrated their 49th wedding anniversary under its tents, Easton said. Most of the field hospital's patients -- including the couple -- have been successfully discharged.
