TB vaccine could assist future COVID-19 vaccine development

 Despite unprecedented efforts to develop COVID-19 vaccines in record time amid the global pandemic, SARS-CoV-2 continues to spread rapidly with the emergence of new variants, such as delta and omicron, making the development of new therapeutic strategies critically important.

Preliminary studies early in the pandemic found evidence that countries with Bacillus Calmette-Guérin (BCG) vaccination programs, which fights tuberculosis, could be associated with a reduced number and/or severity of COVID-19 cases. While clinical trials are ongoing to further investigate, a University of Houston computational biology researcher is reporting cross reaction between the two illnesses that might help explain what could be driving immunity brought on by the BCG vaccination.

"The protection against SARS-CoV-2 induced by BCG vaccination may be mediated by cross-reactive T cell lymphocytes, which recognize peptides displayed by class I Human Leukocyte Antigens (HLA-I) on the surface of infected cells," reports Dinler Amaral Antunes, assistant professor of computational biology and a corresponding author of the work published in the journal Frontiers in Immunology.

The researchers from UH, Pontifical Catholic University of Rio Grande do Sul and Rice University, implemented a large-scale computational screening to identify potential targets with biochemical similarities between the two illnesses.

T cell lymphocytes develop from stem cells and help protect the body from infection. T cell responses to SARS-CoV-2 are vital for helping resolve viral infections and protecting against reinfection by providing long-lasting immunity. Peptides are chains of amino acids connected to one another which can be derived from proteins of the virus, as well as from proteins of the host. HLAs are receptors that display these peptides to the immune system.

The research team screened over 13.5 million possible cross-reactive peptide pairs from BCG and SARS-CoV-2. The analysis produced a large dataset of cross-reactive clusters, which ultimately led to the identification of 40 peptide pairs with potential cross-reactivity with BCG peptides.

The top 40 list includes SARS-CoV-2-derived peptides GEAANFCAL, GEVITFDNL and FIAGLIAIV which have been independently shown to induce T cell response, Interferon Gamma (INF-γ) production and lymphocyte proliferation in COVID-19 patients. INF-γ is a critical component of immunity against viral and some bacterial infections.

"In addition, multiple peptides from our top 40 list have been reported to induce T cell activation in recent studies analyzing aspects of cellular immunity in COVID-19 patients," said Antunes. "The development of peptide-based vaccines targeting coronaviruses and presenting cross-reactivity with existing pools of memory T cells, could be an interesting strategy to complement and extend the protection conferred by existing COVID-19 vaccines."

The research team includes co-author André Fonseca, a postdoctoral researcher working in the Antunes lab; Ana Paula D. De Souza, Tiago C. Ferreto, Renata F. Tarabini, Rafael Bele and Felipe Rubin of Pontifical Catholic University of Rio Grande do Sul, Brazil; and Lydia E. Kavraki, Mauricio Menegatti Rigo of Rice University.

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Story Source:

Materials provided by University of Houston. Original written by Laurie Fickman. Note: Content may be edited for style and length.

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Journal Reference:

1. Renata Fioravanti Tarabini, Mauricio Menegatti Rigo, André Faustino Fonseca, Felipe Rubin, Rafael Bellé, Lydia E Kavraki, Tiago Coelho Ferreto, Dinler Amaral Antunes, Ana Paula Duarte de Souza. Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2. Frontiers in Immunology, 2022; 12 DOI: 10.3389/fimmu.2021.812176

https://www.sciencedaily.com/releases/2022/01/220113151359.htm

Heart disease causes early brain dysfunction, can treble key Alzheimer’s protein

 Heart disease can directly cause brain dysfunction early on which could lead to dementia and can treble the amount of an Alzheimer's protein in the brain, say scientists.

The new research, published in eLife, has found that heart disease causes a breakdown of a key brain function which links brain activity and blood flow, meaning the brain gets less blood for the same amount of activity.

This is happening in heart disease patients before the build up of fat in the brain's blood vessels (atherosclerosis) and is a prelude to dementia. Until now it has been unclear how some forms of vascular dementia can happen years before atherosclerosis in the brain.

The researchers also discovered that the combination of heart disease and a genetic predisposition for Alzheimer's Disease trebles the amount of beta-amyloid, a protein that builds up and triggers Alzheimer's, and increases the levels of an inflammatory gene (IL1) in the brain.

Dr Osman Shabir, lead author of the study from the University of Sheffield's Neuroscience and Healthy Lifespan Institutes, said: "Alzheimer's Disease is the most common form of dementia worldwide and heart disease is a major risk factor for both Alzheimer's and dementia. The new findings are key to furthering our understanding of the links between heart disease and dementia.

"We've discovered that heart disease in midlife causes the breakdown of neurovascular coupling, an important mechanism in our brains which controls the amount of blood supplied to our neurons. This breakdown means the brain doesn't get enough oxygen when needed and in time this can lead to dementia."

The team have since been awarded a three year grant by the British Heart Foundation to look at the use of an arthritis drug which targets IL1 to see if it could reverse or reduce the brain dysfunction seen to be caused by heart disease.

The team also found that brain injuries can also worsen brain blood flow regulation, supporting observations that patients' symptoms often worsen after injuries or falls.

Story Source:

Materials provided by University of Sheffield. Note: Content may be edited for style and length.

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Journal Reference:

1. Osman Shabir, Ben Pendry, Llywelyn Lee, Beth Eyre, Paul S Sharp, Monica A Rebollar, David Drew, Clare Howarth, Paul R Heath, Stephen B Wharton, Sheila E Francis, Jason Berwick. Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease. eLife, 2022; 11 DOI: 10.7554/eLife.68242

https://www.sciencedaily.com/releases/2022/01/220113120734.htm

Mass. gov keys new hospital policies to combat staffing shortages

 Massachusetts Gov. Charlie Baker (R) implemented new hospital policies on Friday to combat staffing shortages and maintain hospital capacity amid a surge in coronavirus cases.

The governor's administration in a press announced adjustments amid a "critical staffing shortage" that has played a part in the loss of hundreds of hospital beds since the the beginning of 2021.

The administration said that under the new policy, qualified physician assistants will be allowed to practice independently, greater staffing flexibility will be given to dialysis units, foreign-trained physicians will be able to obtain their licensure more easily and nonemergency visits to emergency departments will be discouraged.

"Our healthcare system continues to experience significant workforce and capacity constraints due to longer than average hospital stays, separate and apart from the challenges brought on by COVID,” said Massachusetts Secretary of Health and Human Services Marylou Sudders. 

“Working closely with our hospital leaders, these additional actions by DPH will allow for flexibility to preserve our hospital capacity in the coming weeks,” Sudders added.

The state's Department of Public Health said that hospitals have seen an increase in patients, with a majority from non-COVID-19 related issues.  

Some health experts believe hospitals are seeing an increase in non-coronavirus-related visits because these patients did not seek medical attention previously due to the pandemic. 

Other hospitals in the country have been overwhelmed by an influx of COVID-19 patients amid the rapid spread of the omicron variant, first identified in South Africa last November. 

According to Department of Health and Human Services data released this week, at least 18 states have less than 15 percent capacity in their ICUs. 

The states include Delaware, Georgia, Massachusetts, Mississippi, Missouri, Nevada, New Mexico, North Carolina, Ohio, Oklahoma, Pennsylvania, Rhode Island, Texas, Vermont, Kentucky, Alabama, Indiana and New Hampshire.  

New Hampshire has deployed National Guard personnel to help relieve hospitals and longterm care facilities amid the spike in cases. Federal teams are expected to deploy to other ailing states for assistance. 

https://thehill.com/homenews/state-watch/589865-massachusetts-governor-implements-new-hospital-policies-to-combat

Omicron hits sanitation workers as garbage pick-ups suffer

 

• Cities across the country are struggling to pick-up garbage and recyclables due to staffing shortages driven by the rapid rise of COVID-19 cases.
• In Nashville, the city had to completely stop picking up recyclables because of staffing and fleet issues.
• In Baltimore, the Department of Public Works at one point had 340 employees out over a seven-day period during the holidays.

Industries across the board are suffering from staffing shortages due to rising cases of COVID-19 fueled by the omicron variant, and that’s caused garbage and recycling to pile up on curbsides across the country as states suffer from a lack of sanitation workers. 

The Solid Waste Association of North America (SWANA) warned localities last month that an increase in delays in garbage collection were likely to occur over the holidays and into the new year, due to a sharp rise in new COVID-19 infections. SWANA said staffing shortages were likely and that local sanitation departments could suffer. 

“A substantial percentage of front-line collection workers are not vaccinated, and some may get sick from COVID in the coming weeks. This could make it difficult for some haulers or local sanitation departments to fulfill all of their collection obligations,” said SWANA CEO David Biderman. 

That seems to be the precise position many cities are in, as they announce adjusted pick-up schedules because of the lack of staff.  

This week the Baltimore City Department of Public Works (DPW) announced it would move to a bi-weekly recycling schedule until further notice due to staffing challenges. Jason Mitchell, director of DPW, said the agency has experienced “severe” staffing shortages over a seven-day period during the holidays and averaged 228 employees out of work. The peak was when 340 employees were out during that same period. 

“This change to bi-weekly recycling collections will help the department manage for the long-term. These modifications are essential to stabilize operations and ensure consistent, predictable, and sustainable services for residents,” said Mitchell. 

The city of Philadelphia found itself in a similar situation, with its Streets Department announcing on Twitter that it anticipated collection delays the first week of January due to a high number of COVID-19 infections among staff. 

Liliana Bakhtiari, Atlanta City Council member, told The Associated Press that because of worker shortages, recycling and yard waste will be picked up “as staffing allows.”  

The staffing shortages and pickup disruptions come just as Americans come off the holiday season involving lots of trash, from Christmas gifts that involved boxes, wrapping paper and more. 

According to the AP, sanitation workers in New York City, which has the largest municipal sanitation force in the world, are working longer hours to clear the backlog of waste, as the city has not suspended any services.  

In Nashville, where staffing shortages and delays have gotten so severe that the city is completely stopping recycling pick-up for now, city officials are urging residents to use reusable plates and dishes to minimize waste, among other tips. The city has offered residents to drop off their recyclables themselves at drop-off sites. 

https://thehill.com/changing-america/enrichment/education/589837-omicron-hits-sanitation-workers-as-garbage-pick-ups

Supreme Court handcuffs Biden on vaccinations

 The Supreme Court’s ruling against vaccine-or-test rules for businesses dealt a major blow to the Biden administration's efforts to combat the pandemic, leaving them without many more tools to boost the number of people vaccinated against COVID-19. 

Private businesses can decide for themselves whether to impose a mandate, but without the legal cover, it's unlikely there will be many more doing so, especially in GOP-led states that have made mandates illegal. A federal rule would have preempted state policy, allowing businesses to keep their mandates in place.

Congressional Republicans and GOP state officials celebrated the ruling, saying the Supreme Court stood up for the freedoms of individual people.

“The Supreme Court just BLOCKED Biden's authoritarian vaccine mandate for businesses,” tweeted House Minority Whip Rep. Steve Scalise (R-La.). “But let's be clear: This doesn’t go far enough. Health care workers should NOT be subjected to this tyrannical mandate either.”

Health experts say there’s clear evidence that mandates work in getting more people vaccinated, and they fear that without one for nearly 80 million workers, more people will be at risk of getting hospitalized and dying.

“It is now highly unlikely that the U.S. will hit the 85-90% of Americans vaccinated to get to the other side of the pandemic,” tweeted Celine Gounder, an infectious disease specialist and former member of the Biden administration's transition team. 

President Biden has indicated he is running out of patience with Americans who refuse to get vaccinated against the coronavirus. Cash giveaways, dating app partnerships and even free college tuition were barely moving the needle, so the rules were necessary to force the issue and make workplaces safer. 

But the Supreme Court said the largest stick is unconstitutional, and it's not clear that the White House has any tools left that officials want to use. 

Lawrence Gostin, a public health law professor at Georgetown University, said President Biden should mandate COVID-19 vaccines for domestic travel.

“He has wide authority over regulating the travel industry, and he’s already lawfully required masks in airports and on planes. He could do the same thing with vaccines, just like he requires it for international travelers,” Gostin said.

But airlines and other business groups oppose any vaccine and testing requirement for domestic air travel, and White House chief medical adviser Anthony Fauci recently suggested that the administration isn’t going to implement anything to get more people vaccinated.

According to Centers for Disease Control and Prevention data, about 67 percent of the eligible U.S. population is fully vaccinated. The remaining group of unvaccinated holdouts is in large part fueling the more than 1,700 deaths a day from COVID-19 occurring in the U.S. 

As the omicron variant rips through the country, hospitals and health systems are being overwhelmed in many places because of unvaccinated patients. 

“Public health shows that mandates are the only thing that really boost vaccination. We've tried encouragement and pleading, we've tried incentives. The only thing that works is a well-targeted mandate,” Gostin said.

An analysis from the Kaiser Family Foundation found recently there were a total of 690,000 vaccine-preventable COVID-19 hospitalizations from June through November 2021, a period that overlaps with the delta variant surge. The costs of treating these patients over that six-month period was $13.8 billion.

“That [cost] could have been prevented if people had chosen to get vaccinated. It's hard to project how the pandemic sort of plays out. But prevention measures do reduce longer term costs. These are preventable deaths and hospitalizations,” said Krutika Amin, a KFF associate director. 

Health officials stress that the more people get vaccinated who are eligible, the quicker the pandemic will end. During remarks at the White House on Thursday, President Biden continued to characterize the strain on hospitals as a “pandemic of the unvaccinated.”

“Right now, both vaccinated and unvaccinated people are testing positive,” Biden said, “but what happens after that could not be more different.”

Republicans are also attacking Biden for not getting the pandemic under control. The ruling gives them more ammo to wield after 27 Republican-led states sued along with businesses to effectively end the employer rules.

“The Supreme Court has spoken, confirming what we all knew: Biden's disastrous mandates are unconstitutional. Biden promised to shut down the virus, not the economy but he has failed miserably on both — and mandates would have further destroyed the economy. We are proud of the Supreme Court for not backing down. No mandates!" said former President Trump in a statement Thursday.

Gostin said he wishes the Supreme Court and politicians stayed out of public health. 

“The Supreme Court really handcuffed the president's COVID response and I think that's disgraceful. You're in the middle of a pandemic. And I think it'll come back to haunt us when the next crisis arises,” Gostin said.

https://thehill.com/policy/healthcare/589855-supreme-court-handcuffs-biden-on-vaccinations

Legendary Bayer is Reinventing its Story with Cell and Gene Therapy

 For the past few years, pharma giant Bayer has transformed its pipeline by acquiring multiple cell and gene therapy companies to create new opportunities. This has allowed the company to provide life-saving and life-altering therapies to patients with different disease types.

The new approach has energized the Germany-based life sciences giant known for inventing aspirin, its leading position in chemistry and the advancement of small molecules. Through multiple acquisitions, Bayer has bolted on new cutting-edge programs in four key areas of focus—iPSC, allogenic CAR-T, genome mutations, and gene editing. One year ago, Marianne De Backer, Ph.D., head of business development & licensing in Bayer’s pharmaceuticals division, told BioSpace that Bayer had to find pioneers in these fields and bring them into the fold to achieve its transformative goal. The move is beginning to show the fruit that will validate that decision.

On Tuesday, Christian Rommel, Ph.D., head of research and development t at Bayer, told BioSpace that he credits the Bayer leadership team for the “courage and vision” to lead the storied company through a new era. Rommel joined Bayer in early 2021 after spending seven years at Roche in various roles, including global head of oncology pharma research & early development. He was attracted to the company’s changes with the launch of the cell and gene therapy platform developed within its pharmaceutical division. The 150-year-old company established the platform to advance new approaches to treating a myriad of diseases.

“We are reinventing our story and becoming strong in new areas of the sciences,” Rommel said. “We look very different than we did a year ago.”

Rommel spoke to BioSpace the day after the company forged a collaboration with Mammoth Biosciences for their CRISPR technology expected to be used to develop in vivo gene-editing therapies. The companies plan to harness the CRISPR technology across five preselected in vivo indications, with the first focus on liver-targeted diseases. Rommel expressed his excitement about the potential of CRISPR technology and the promise that it can provide for patients with rare diseases.

“The Mammoth technology is a therapeutic approach in its own right. We will consider enabling that approach and plan to build a pipeline with them,” he said.

The potential that technology like CRISPR and other cell and gene therapy approaches offers to patients has had Bayer excited enough to open the purse strings and bolster its pipeline.

“You need a little bit of financial resources to keep innovating,” Rommel quipped. He then noted that these kinds of approaches have broken new ground in medicine and offer a glimmer of hope in developing cures for devastating diseases. “There is high risk in cell and gene therapy. But the rewards are promising.”

Rommel pointed to Bayer subsidiary BlueRock Therapeutics, acquired in 2019, and its pluripotent stem cell-derived dopaminergic neuron study in Parkinson’s disease. Last week, BlueRock closed out its first two cohorts in an open-label Phase I study. Ultimately, the company hopes its approach will replace lost neurons in the midbrain region of Parkinson’s disease patients. This could regenerate lost function in the brain and potentially reverse the disease.

“With BlueRock, we’re doing something that makes a lot of sense, but is so hard to do,” Rommel said. He said they are committed to the program but recognize that there are still hurdles to overcome. 

In addition to BlueRock, Bayer also acquired AskBio in 2020 and partnered with Atara Biotherapeutics to develop off-the-shelf T-cell immunotherapies for high mesothelin-expressing tumors. And, just a few months ago, Bayer snapped up San Diego-based Vividion Therapeutics and its protein surface screening program. Rommel said the acquisition of Vividion will become a cornerstone of its new strategy to develop innovative therapies. Vividion’s technology platform uses chemoproteomics, chemistry and biology to find drug targets in previously “undruggable” proteins.

Rommel is keen on Vividion’s position under the Bayer umbrella. He said the innovation taking place at Vividion combined with the muscle of Bayer would lead to the development of first-in-class drug candidates that can provide new therapies for patients who are not well-served by existing treatments.

“It’s a very good strategic fit,” he said.

As part of its evolution, Bayer has taken a different approach with its recent acquisitions. The companies are brought under the Bayer umbrella, but they operate independently, at arm’s length. This approach aims to let companies maintain that sense of independence to foment entrepreneurial and scientific cultures. And that’s an approach that is paying off. Rommel disclosed that Bayer’s “arm’s length” approach appealed to Vividion. The company had been in the midst of an initial public offering when Bayer approached them with the acquisition offer. The San Diego company ultimately dropped the plans to go public to come under the Bayer umbrella.

“Vividion can be Vividion. They can do the innovative discovery work they set out to do,” he said.

While Bayer continues to assess mergers and acquisitions to advance its new cell and gene therapy division, Rommel noted that the coming months will be crucial as data come in from various programs the company has bought into with its aggressive investment strategy. He noted the company would have successes and failures, but what they learn from both will lead to better innovations for patients.

“For any R&D organization, it’s important to do this kind of work because it’s so inspirational and aspirational,” he said.

https://www.biospace.com/article/with-multiple-cell-and-gene-therapy-deals-bayer-looks-to-a-promising-horizon/

SCOTUS Says Biden Can't Enforce A Vaccine Mandate, But Blackstone Will Anyway

 The Supreme Court Thursday blocked the Occupational Safety and Health Administration's nationwide worker vaccine mandate, but some U.S. employers are still moving forward with requiring employees to get Covid-19 booster shots, with Blackstone the latest to join a league of Wall Street firms announcing new vaccine mandates. 

Unsplash/Chenyu Guan

The New York-based investment firm with a huge commercial property portfolio told employees they must get boosters “as soon as practically possible,” according to a Bloomberg report. Employees will not be able to return to the office if they fail to do so. The company said it will also be testing employees in the office three times a week. 

Other Wall Street firms taking similar measures include Goldman Sachs Group, which announced its booster mandate last month. JPMorgan Chase CEO Jamie Dimon said this week the firm is not allowing unvaccinated workers in the office, and “we’re not going to pay you not to work in the office.” 

An emergency measure by OSHA went into effect this week in which workers at businesses with 100 or more employees must get vaccinated or submit to weekly Covid testing to enter the workplace. The Supreme Court has blocked the Biden administration from enforcing these measures, which could result in an easing of rules for U.S. companies that aren’t creating their own mandates.

Blackstone is one of several companies that has delayed its return-to-office plans. It first asked U.S. staff to return to the office full time by June 2021, and that date has been kicked to Jan. 28 after several variants, the newest being omicron, prompted employers to rethink timelines. 

Facebook’s parent company, Meta, delayed its U.S. office reopening date to March 28 from Jan. 31, and it will be mandating booster shots for those returning to the office, according to Reuters. 

“Employees who take no action can face disciplinary measures, including termination. Obviously, this would be a last resort,” a spokesperson told Reuters. 

Google told employees last month they could lose their job if they don’t comply with vaccination policies. 

There were 740,594 Covid cases reported each day on average over the week leading to Jan. 10, its highest point yet, according to NBC News. The U.S. reported about 1.3 million cases in total on Monday, beating the previous record of 1 million set on Jan. 3. 

This surge in cases in part prompted dissension from liberal Justices Stephen Breyer, Sonia Sotomayor and Elena Kagan regarding the Supreme Court ruling. 

“In the face of a still-raging pandemic, this Court tells the agency charged with protecting worker safety that it may not do so in all the workplaces needed,” they said in their dissent.

https://www.bisnow.com/national/news/office/get-boosted-or-dont-come-to-work-blackstone-joins-wall-street-firms-in-vaccine-mandate-111505