Mutation-mapping tool could yield stronger COVID boosters, universal vaccines

 Researchers at the University of Colorado Boulder have developed a platform which can quickly identify common mutations on the SARS-CoV-2 virus that allow it to escape antibodies and infect cells.

Published today in Cell Reports, the research marks a major step toward successfully developing a universal vaccine for not only COVID-19, but also potentially for influenza, HIV and other deadly global viruses.

"We've developed a predictive tool that can tell you ahead of time which antibodies are going to be effective against circulating strains of virus," said lead author Timothy Whitehead, associate professor of chemical and biological engineering. "But the implications for this technology are more profound: If you can predict what the variants will be in a given season, you could get vaccinated to match the sequence that will occur and short-circuit this seasonal variation."

The research team's secret ingredient? Baker's yeast.

They developed a genetically modified version of this innocuous material to express some of SARS-CoV-2's viral spike proteins along the yeast's surface, with which they can map resulting mutations that form and escape neutralizing antibodies. The resulting roadmap could inform the development of more effective booster vaccines and tailored antibody treatments for patients with severe cases of COVID-19, said Whitehead.

The key to the crown

Spike proteins are sharp bumps that stick out from the surface of viruses in the coronavirus family. Under a microscope, they can appear like a crown, which is where coronaviruses— corona being Latin for "crown"—gain their name, and how they bind to cells like a key in a lock. When antibodies recognize them, latch on, and prevent them from binding to cells, they prevent infection.

But when spike proteins mutate, antibodies do a double take.

"There are mutations on the spike protein that prevent an antibody from going in and recognizing it. Just like getting a new haircut, you look like a different person; this looks like a different virus to that antibody," said Whitehead.

In the case of the more contagious Delta variant that emerged in 2021, mutations on the spike proteins have made it more contagious and reduced the efficacy of some antibody therapies.

What if there was a way to predict which mutations could emerge next—and therefore prepare for them? Earlier this year, Whitehead's team set out to find a way.

What comes after Delta?

Some antibodies which can bind to different locations have been used in treatment cocktails given to COVID-19 patients. But the strains of the virus now circulating within the U.S. are different enough that some of these antibody therapies no longer seem effective, said Whitehead.

So first, the researchers needed to identify mutations on the spike protein that could prevent these antibodies from working. Then they wanted to predict what mutations are likely to occur next—what could become the zeta, eta or theta variant?

"When the pandemic started, we saw the opportunity to apply techniques mastered by our lab to make a contribution," said Irene Francino-Urdaniz, co-author on the paper, graduate student in chemical and biological engineering and a Balsells fellow. "When a new variant was detected, based on my research, I could most of the times guess which mutations were present. I am very excited to have contributed with my work not only to this pandemic but possibly to future vaccines."

Francino-Urdaniz developed a genetically engineered strain of common baker's yeast, which could display different portions of the viral spike protein on its surface. She then discovered how to screen through thousands of mutations in a single test tube to find the ones that evaded neutralizing antibodies.

As some home-bound bakers discovered in 2020 while experimenting with sourdough starters, yeast grows quite quickly. This means that the researchers can see a wide variety of mutations develop at the same speed at which the yeast can grow—leaps and bounds faster than the rate at which mutations will emerge in real time. This could give scientists an invaluable head start.

A universal vaccine

The researchers have already found some of the same mutations now circulating the globe, as well as identified more mutations with the potential to evade our immune systems. They will also provide all their libraries of information, methods and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2.

This means the next COVID-19 vaccine or booster shot produced for the public could have the ability to pack the most punch possible. It also gives hope for those who are immunocompromised or remain at a higher risk of contracting a bad case, as this research can be applied to proactively prepare antibody cocktails for specific mutations, giving them a better chance at survival and recovery.

But the promise doesn't stop there. Due to the adaptability of new mRNA vaccines which work with spike proteins, the applications of this research are not limited to one virus, said Whitehead.

"You can use it for mapping trajectories for influenza and for HIV potentially; for other viral diseases that are known, and also potentially emerging pandemic ones," he said.

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New 'atlas' charts how antibodies attack spike protein variants

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More information: Irene M. Francino-Urdaniz et al, One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.109627

https://medicalxpress.com/news/2021-08-mutation-mapping-tool-yield-stronger-covid.html

Global eradication of COVID-19 probably feasible

 The global eradication of COVID-19 is probably feasible, and more so than it is for polio, although considerably less so than it was for smallpox, suggests a comparative score of technical, sociopolitical, and economic factors for all three infections, published in the online journal BMJ Global Health.Vaccination, public health measures, and global interest in achieving this goal as a result of the huge financial and social havoc wrought by the coronavirus pandemic, all make eradication possible.

But the main challenges lie in securing sufficiently high vaccine coverage and being able to respond quickly enough to variants that may evade immunity, say the authors.

To estimate the feasibility of COVID-19 eradication, defined as 'the permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts', the authors compared it with two other viral scourges for which vaccines were/are available—-smallpox and polio—using an array of technical, sociopolitical, and economic factors that are likely to help achieve this goal.

They used a three point scoring system for each of 17 variables. These included: factors such as the availability of a safe and effective vaccine; lifelong immunity; impact of public health measures; effective government management of infection control messaging; political and public concern about the economic and social impacts of the infection; and public acceptance of infection control measures.

Smallpox was declared eradicated in 1980 and two out of the three serotypes of poliovirus have also been eradicated globally.

The average (total) scores in the analysis added up to 2.7 (43/48) for smallpox, 1.6 (28/51) for COVID-19, and 1.5 (26/51) for polio.

"While our analysis is a preliminary effort, with various subjective components, it does seem to put COVID-19 eradicability into the realms of being possible, especially in terms of technical feasibility," they write.

They acknowledge that relative to smallpox and polio, the technical challenges of COVID-19 eradication include poor vaccine acceptance, and the emergence of more highly transmissible variants that may evade immunity, potentially outrunning global vaccination programmes.

"Nevertheless, there are of course limits to viral evolution, so we can expect the virus to eventually reach peak fitness, and new vaccines can be formulated," they explain.

"Other challenges would be the high upfront costs (for vaccination and upgrading health systems), and achieving the necessary international cooperation in the face of 'vaccine nationalism' and government-mediated 'antiscience aggression'," they admit.

The persistence of the virus in animal reservoirs may also thwart eradication efforts, but this doesn't appear to be a serious issue, they suggest.

On the other hand, there is a global will to tackle the infection. The massive scale of the health, social and economic impacts of COVID-19 in most of the world has generated "unprecedented global interest in disease control and massive investment in vaccination against the pandemic," they point out.

And unlike smallpox and polio, COVID-19 also benefits from the added impact of public health measures, such as border controls, social distancing, contact tracing and mask wearing, which can be very effective if deployed well.

The upgrading of health systems to get rid of the virus could also aid the control of other infections and even help eradicate measles, they suggest.

"Collectively these factors might mean that an 'expected value' analysis could ultimately estimate that the benefits outweigh the costs, even if eradication takes many years and has a significant risk of failure," they write.

Elimination of COVID-19, defined as 'reduction to zero of the incidence of infection caused by a specific agent in a defined geographical area as a result of deliberate efforts', has been achieved and sustained for long periods in several jurisdictions in the Asia-Pacific region, providing proof-of-concept that global eradication is technically possible, they note.

They acknowledge that their study is preliminary, and more extensive in-depth work is required. The World Health Organization, or a coalition of national-level agencies working collaboratively, needs to formally review the feasibility and desirability of attempting COVID-19 eradication, they conclude.

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Herd immunity appears unlikely for COVID-19, but CDC says vaccinated people can ditch masks in most settings

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More information: We should not dismiss the possibility of eradicating COVID-19: comparisons with smallpox and polio, BMJ Global Health (2021). DOI: 10.1136/bmjgh-2021-006810

https://medicalxpress.com/news/2021-08-global-eradication-covid-feasible-polio.html

Senate Democrats seek to overhaul nursing home industry

 Senate Democrats on Tuesday introduced legislation aimed at bolstering nursing home staffing, transparency, accountability and oversight, after COVID-19 wreaked havoc on seniors in long-term care facilities.   

The bill, from a group led by Sens Ron Wyden (D-Ore.) and Bob Casey (D-Pa.), proposes a series of comprehensive changes to an industry that advocates and lawmakers have said is in need of reform.

Nursing home residents make up only a tiny fraction of the U.S. population, but they were disproportionately killed by COVID-19. According to federal figures,almost one in three COVID-19 deaths in the U.S. were connected to nursing homes. 

Nursing homes across the country essentially locked down in March 2020, but health experts believe staff still unwittingly brought infections into the facilities, unleashing rapid outbreaks. Residents were not truly protected until vaccines became available, almost a year since the first reported outbreak.

Even now, low vaccination rates among nursing home staff are threatening the progress the nation has made in protecting the vulnerable elderly. 

“Families must have faith that loved ones receiving long-term care or care after a hospital stay will be safe and receive good-quality care,” Wyden said in a statement. 

“The pandemic, myriad reports of abuse, and critical failures during natural disasters have shattered that foundation of trust and safety. This legislation represents a big step towards nursing home care that is safer, higher quality, more accountable and more supportive of the workers who care for our most vulnerable."

Among other provisions, the legislation would end the practice of advance binding arbitration agreements, where nursing homes require families and residents to waive their rights to sue over disputes involving care, as a condition of admittance and residency.

The bill would also require nursing homes to meet minimum staffing standards to avoid quality problems. It would require a registered nurse to be available 24 hours a day instead of the current eight, and require nursing homes to hire a full-time infection control and prevention specialist.

The bill would provide temporary additional federal resources through Medicaid to increase wages and support the recruitment and retention of staff, as well as support improvements in resident care. 

The American Health Care Association and National Center for Assisted Living (AHCA/NCAL), a leading nursing home trade group, has been lobbying for more federal funding in order to fix what they say are chronic issues facing the industry. In a statement, AHCA said it welcomed "the initial steps offered in this bill," particularly the enhanced Medicaid funding, but said more is needed.

Specifically, the group questioned the effectiveness of minimum staffing requirements without a permanent funding source.

"Providers will not be able to meet staffing requirements if we can’t find people to fill the open positions. There must be a comprehensive approach to staffing beyond just numbers."  Mark Parkinson, the group's president and CEO, said in a statement. 

The group also said it was strongly opposed to the restrictions on arbitration agreements, which are in place in the majority of nursing homes across the country. 

Advocates argue that arbitration agreements largely favor the corporations that operate nursing homes, as the hearings are held behind closed doors and the results are often obscured by privacy clauses. 

The industry argues arbitration is more efficient and less costly than civil trials.

In 2016, the Obama administration banned nursing homes from including arbitration agreements as part of admissions paperwork. Legal challenges from the industry prevented the rule from taking effect, and President Trump formally revoked the ban shortly after taking office.

https://thehill.com/policy/healthcare/567238-senate-democrats-seek-to-overhaul-nursing-home-industry

Mass. covid breakthrough deaths: 73% had underlying conditions, median age 82.5

 New data from Massachusetts public health officials reveals that a significant majority of fully vaccinated people who died after a coronavirus breakthrough infection had underlying conditions that made them more likely to have a severe case.

Also, the median age of Massachusetts vaccine breakthrough cases who died has been 82.5 years, according to the new data from the state Department of Public Health.

There have been 100 breakthrough case deaths in the Bay State, which is 0.002% of all fully vaccinated individuals, or about two for every 100,000 residents who got their shots. More than 4.3 million people in the state have been fully vaccinated.

Of the 100 breakthrough case deaths, 73% of these cases were reported to have underlying conditions that made them more likely to have severe disease.

Overall, there have been 395 breakthrough hospitalizations, which is 0.009% of all fully vaccinated individuals. Of the 395 hospitalizations, 57% of these patients were reported to have underlying conditions.

This new data is comparable to the data of breakthrough cases in other countries, said Davidson Hamer, a Boston University specialist in infectious diseases.

“The breakthrough cases that are sick enough to be hospitalized is generally older people and those with underlying conditions and who are immunocompromised,” Hamer said. “So the people who need to be really careful right now is older people and those who have underlying conditions and those who are immunocompromised.”

Breakthrough cases have been rising in Massachusetts in recent weeks amid the spread of the more highly contagious delta variant.

The state last week reported that 7,737 fully vaccinated people have tested positive for COVID-19, a jump of 1,364 cases in one week, or a daily average of 195 cases.

The 7,737 breakthrough cases is 0.18% of the 4.3 million fully vaccinated people in Massachusetts.

“Breakthrough cases in Massachusetts are incredibly low, and those hospitalized or who have died are even lower,” the DPH said in a statement. “All available data continue to support that all 3 vaccines used in the US are highly protective against severe disease and death from all known variants of COVID-19. The best way to protect yourself and your loved ones is to get vaccinated.”

Deaths from breakthrough infections is “very uncommon,” said Todd Ellerin, director of infectious diseases at South Shore Health.

“But when it happens, it’s usually those who are elderly or immunocompromised,” Ellerin said, stressing, “The vaccine has shown that it’s been extremely protective in the elderly.”

Booster shots could be coming soon for certain groups.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said on “Meet The Press” Sunday that those who are immunocompromised and got vaccinated, “likely never got a good response to begin with.”

“For those individuals, I am strongly in favor of getting them that additional shot as soon as possible,” said Fauci, who serves as chief medical adviser to President Biden.

Those who are elderly will likely get a booster before other groups, Fauci said, based on data of the vaccine’s effectiveness over time.

https://www.bostonherald.com/2021/08/08/massachusetts-coronavirus-breakthrough-deaths-73-had-underlying-conditions-median-age-was-82-5/

18% of migrant families leaving Border Patrol custody tested positive for Covid

 More than 18 percent of migrant families and 20 percent of unaccompanied minors who recently crossed the U.S. border tested positive for Covid on leaving Border Patrol custody over the past two to three weeks, according to a document prepared this week for a Thursday briefing with President Joe Biden.

Some flights scheduled to deport migrants had more than 25 percent of passengers test positive before departure, leading Immigration and Customs Enforcement to remove those migrants from the flights for quarantine in the U.S., according to the document.

The Department of Homeland Security document does not give precise dates or say how many migrants were tested.

Migrants are not tested for Covid in Border Patrol custody unless they show symptoms, but all are tested when they leave Border Patrol custody, according to DHS officials. Immigrants who are allowed to stay in the U.S. to claim asylum are given tests when they are transferred to ICE, Health and Human Services or non-governmental organizations. Deportees who are scheduled to be put on planes out of the U.S. are tested for Covid and other infectious diseases by ICE.

As of Wednesday, more than 15,000 migrants were in Border Patrol custody, according to Customs and Border Protection data obtained by NBC News.

Former federal employees allege 'hundreds' of children contracted Covid at overcrowded HHS shelter

JULY 28, 202103:48

If a migrant who is about to be deported by ICE tests positive for Covid, the migrant is quarantined and deportation is delayed, according to DHS. The document refers specifically to those migrants chosen for "expedited removal," meaning they were deported soon after they crossed or attempted to cross the U.S. border.

"In the last 2-3 weeks, the percent positivity rates among all demographics has increased," the document says.

The document also recommends DHS provide more medical staffing at border processing facilities, citing one in the Rio Grande Valley where three EMTs were responsible for 3,000 migrants.

A second DHS document prepared this week for the White House says high positivity rates are "straining the capacity of the NGOs and local governments that DHS currently partners with to care for them."

That document attributes the rise of Covid among undocumented immigrants to "the highly transmissible Delta variant combined with lengthier stays in crowded [Customs and Border Protection] facilities."

The high rates have triggered emergency meetings between the White House, HHS and DHS this week, according to two sources with knowledge of the discussions.

Border Patrol makes 210,000 apprehensions in July

AUG. 4, 202102:19

The briefing materials make clear that the high number of Covid-positive migrants is slowing down the deportation of families, an effort the administration ramped up in late July.

In a statement, a White House spokesperson said, "DHS and CBP takes its responsibility to prevent the spread of Covid-19 and other diseases very seriously. CBP provides migrants who can't be expelled...or are awaiting processing with PPE from the moment they are taken into custody, and migrants are required to keep masks on at all times, including when they are transferred or in the process of being released. If anyone exhibits signs of illness in CBP custody, they are referred to local health systems for appropriate testing, diagnosis, isolation and treatment."

The Biden administration is considering testing all migrants in Border Patrol custody, according to the second document, but CBP, the Border Patrol's parent agency, does not currently have the testing capability.

Deputy Border Patrol Chief Raul Ortiz, who will soon take over as chief, told NBC News on Wednesday that such testing would lead to further bottlenecks in the Border Patrol's facilities.

"As you can see, we're already overwhelmed," Ortiz said, standing next to a bridge in Del Rio, Texas, where hundreds of migrants have been held at a time, sleeping on the ground, as border processing facilities are stretched six times past their capacity

On Tuesday, CBP stopped 6,725 undocumented immigrants crossing into the U.S., according to internal data obtained by NBC News, keeping with the daily pace of July, which saw 210,000 total apprehensions, a 21-year high.

Of the more than 6,700 stopped, more than 900 were unaccompanied children, a demographic that continues to increase, according to the data.

https://www.nbcnews.com/news/ncna1276244

Gottlieb: Covid delta surge may be ‘final wave’ in U.S.

 Dr. Scott Gottlieb told CNBC on Monday the current surge in Covid infections caused by the more contagious delta variant may be the “final wave” of the virus in the United States.

“I don’t think Covid is going to be epidemic all through the fall and the winter. I think that this is the final wave, the final act, assuming we don’t have a variant emerge that pierces the immunity offered by prior infection or vaccination,” the former Food and Drug Administration commissioner said on “Squawk Box.” “This is probably going to be the wave of infection that ends up affecting the people who refuse to get vaccinated.”

Gottlieb said Americans have a couple months remaining where they need to take pandemic-related precautions, particularly in northern U.S. states as cases begin to peak in the South, until the wave of infections begins to decrease again.

“I think this is going to be a difficult period right now,” he said. However, Gottlieb said the contagious nature of the delta variant and increased vaccination rates could change the trajectory of future infections.

“We’re going to reach some level of populationwide exposure to this virus, either through vaccination or through prior infection that’s going to stop circulating at this level, at this rate,” said Gottlieb, who led the FDA from 2017 to 2019 under the Donald Trump administration.

The seven-day average of new daily coronavirus cases in the U.S. is 108,624, according to a CNBC analysis of Johns Hopkins University data. That’s up 36% compared with one week ago. The highly transmissible delta variant, first identified in India, is estimated to comprise 83% of all sequenced Covid cases in the country, according to Centers for Disease Control and Prevention estimates.

With the surge in infections coinciding with school reopening plans in the fall, Gottlieb warned that schools may need to begin the year with heavier mitigation measures in place like mask-wearing, testing, physical distancing and gathering through pods. 

“The goal has to be to get schools open and keep them open, and we can’t expect to change all the behaviors in terms of what we’re doing with respect to mitigation in schools and get the same result, especially with this new delta variant which is more contagious, and is inevitably going to be hard to control in the schools,” said Gottlieb, who serves on the board of Covid vaccine maker Pfizer.

Large amounts of vaccinated people can still gather in a venue if there is some “semblance of a bubble” around it, he said. Vaccinated people who are getting infected are likely contracting the virus from unvaccinated people, and then spreading it to close contacts after being contagious for a brief window of time, the former FDA chief said.

Gottlieb said wearing a higher-quality mask, like the KN95 mask, is more important now as the virus is known to spread through aerosols and not droplets. A high-quality cloth mask affords only 20% protection from transmission, and most people don’t wear them well, he said.

“We are taking sort of an alpha mindset into a delta world, and it’s not going to work,” Gottlieb said, referring to the alpha coronavirus variant first detected in the U.K. last year. “We’re going to see that this delta variant is more difficult to control,” he said.

https://www.cnbc.com/2021/08/09/dr-scott-gottlieb-says-the-covid-delta-surge-may-be-the-final-wave-in-us.html

Kidney Transplant Recipients Need 3rd COVID Vax Dose? NIH Starts Pilot Study

 

• A trial has been launched to assess the antibody response of the third dose of COVID-19 messenger RNA vaccine in kidney transplant recipients who did not respond to two doses of the Moderna Inc MRNA 5.72% or Pfizer Inc PFE 4.81% - BioNTech SE BNTX 6.87% COVID-19 vaccine. 
• The Phase 2 trial is funded by the NIH’s National Institute of Allergy and Infectious Diseases.
• The pilot study, called COVID Protection After Transplant (CPAT), will enroll up to 200 people aged 18 years or older who received a kidney transplant one year or more before enrollment and have had no recent organ rejection or change in immunosuppression. 
• All participants will have had a low or no detectable antibody response to two doses of an mRNA vaccine.
• The lifelong immunosuppressive therapy that organ transplant recipients must take to prevent organ rejection blunts their immune response to pathogens and vaccines. 
• Research has shown that many organ transplant recipients do not develop antibodies against the COVID-19 vaccine regimen. 
• The purpose of the new study is to determine whether a third dose of one of the mRNA COVID-19 shots could overcome this problem for at least some kidney transplant recipients. 
• The study team will follow participants for one year after enrollment. Preliminary results are expected in September 2021.

https://www.benzinga.com/general/biotech/21/08/22428468/will-kidney-transplant-recipients-need-third-covid-19-vaccine-dose-nih-starts-pilot-study