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Monday, July 26, 2021

Protection by BNT162b2, mRNA-1273 COVID vaccines in fully vaccinated cohorts with/without prior infection

 

Laith J Abu-RaddadHiam ChemaitellyHoussein H. AyoubHADI M. YASSINEFatiha BenslimaneHebah A. Al KhatibPatrick TangMohammad Rubayet HasanPeter CoyleZaina Al KanaaniEinas Al KuwariAndrew JeremijenkoAnvar Hassan KaleeckalAli Nizar LatifRiyazuddin Mohammad ShaikHanan F. Abdul RahimGheyath NasrallahMohamed Ghaith Al KuwariAdeel A ButtHamad Eid Al RomaihiMohamed H. Al-ThaniAbdullatif Al KhalRoberto Bertollini

Rapid mass vaccination against SARS-CoV-2, Variants-of-Concern: Evidence from early VoCs hotspot

 

joerg paetzold, Florian Krammer, Dorothee von Laer, Hannes winner, Janine Kimpel, Katie Bates, Michael Hummer

DOI: 
10.21203/rs.3.rs-741944/v1
PDF: https://www.researchsquare.com/article/rs-741944/v1.pdf?c=1627163208000

We studied the real-life effect of an unprecedented rapid mass vaccination campaign. Following a large outbreak of B.1.351 and B.1.1.7/E484K in the district of Schwaz/Austria, 100,000 BNT162b2 doses were procured to mass vaccinate the entire adult population (16+) of the district between the 11th and 16th of March 2021. This made the district the first widely inoculated region in Europe. We examined the effect of this unique campaign on the number of infections including VoCs, hospital and intensive care unit (ICU) admissions. We compared Schwaz with (i) a control group of highly similar districts, and (ii) with populations residing in municipalities along the border of Schwaz which were just excluded from the campaign. We find large and significant decreases for all outcomes after the campaign, including VoCs cases. The reduction relative to the control regions was largest for younger age cohorts, which were mostly non-vaccinated in the rest of the country due to the age-gradient in the national vaccination plan. Our results demonstrate that rapid population-wide mass vaccination can be an effective tool to curb overall infections as well as VoCs.

https://www.researchsquare.com/article/rs-741944/v1

New understanding of cell stability with potential to improve immune cell therapies

 Research in mice, published today in Science Immunology by researchers at the Babraham Institute, UK and VIB-KU Leuven, Belgium, provides two solutions with potential to overcome a key clinical limitation of immune cell therapies. Regulatory T cells have potential in treating autoimmunity and inflammatory diseases yet they can switch from a protective to damaging function. By identifying the unstable regulatory T cells, and understanding how they can be purged from a cell population, the authors highlight a path forward for regulatory T cell transfer therapy.

Cell therapy is based on purifying cells from a patient, growing them up in cell culture to improve their properties, and then reinfusing them into the patient. Professor Adrian Liston, Immunology group leader at the Babraham Institute, explained their therapeutic potential: "The leading use of cell therapy is to improve T cells so that they can attack and kill a patient's cancer, however the incredible versatility of the immune system means that, in principle, we could treat almost any immune disorder with the right cell type. Regulatory T cells are particularly promising, with their ability to shut down autoimmune disease, inflammatory disease and transplantation rejection. A key limitation in their clinical use, however, comes from the instability of regulatory T cells -- we just can't use them in cell therapy until we make ensure that they stay protective."

T cells come in a large variety of types, each with unique functions in our immune system. "While most T cells are inflammatory, ready to attack pathogens or infected cells, regulatory T cells are potent anti-inflammatory mediators," Professor Susan Schlenner, University of Leuven, explains. "Unfortunately this cell type is not entirely stable, and sometimes regulatory T cells convert into inflammatory cells, called effector T cells. Crucially, the converted cells inherit both inflammatory behaviour and the ability to identify our own cells, and so pose a significant risk of damage to the system they are meant to protect."

The first key finding of this research shows that once regulatory T cells switch to becoming inflammatory, they are resistant to returning to their useful former state. Therefore, scientists need to find a way to remove the risky cells from any therapeutic cell populations, leaving behind the stable regulatory T cells.

By comparing stable and unstable cells the researchers identified molecular markers that indicate which cells are at risk of switching from regulatory to inflammatory. These markers can be used to purify cell populations before they are used as a treatment.

In addition to this method of cell purification, the researchers found that exposing regulatory T cells to a destabilising environment purges the unstable cells from the mixture. Under these conditions, the unstable cells are triggered to convert into inflammatory cells, allowing the researchers to purify the stable cells that are left. "The work needs to be translated into human cell therapies, but it suggests that we might be best off treating the cells mean," says Professor Adrian Liston. "Currently, cell culture conditions for cell therapy aim to keep all the cells in optimal conditions, which may actually be masking the unstable cells. By treating the cultures rougher, we may be able to identify and eliminate the unstable cells and create a safer mix of cells for therapeutic transfer."

Dr Steffie Junius, lead author on the paper who undertook the research as a PhD student at the University of Leuven, commented: "The next stage in the research is to take the lessons learned in mice and translate them into optimal protocols for patients. I hope that our research contributes to the improved design and allows the development of effective regulatory T cell therapy."

Establishing a thorough process to improve cell population stability in mice helps to lay the groundwork for improved immune cell therapies in humans, although the methods described in this work would require validation in humans before they were used in cell therapy trials. Dr Timothy Newton, CEO of Reflection Therapeutics, a Babraham Research Campus-based company designing cell therapies against neuro-inflammation, who was not involved in this study, commented on the translational potential of the study: "This research makes a significant impact on regulatory T cell therapeutic development by characterising unstable subsets of regulatory T cells that are likely to lose their desirable therapeutic qualities and become pro-inflammatory. The successful identification of these cells is of great importance when designing manufacturing strategies required to turn potential T cell therapeutics into practical treatments for patients of a wide range of inflammatory disorders."


Story Source:

Materials provided by Babraham InstituteNote: Content may be edited for style and length.


Journal Reference:

  1. Steffie Junius, Adamantios V. Mavrogiannis, Pierre Lemaitre, Margaux Gerbaux, Frederik Staels, Vanshika Malviya, Oliver Burton, Václav Gergelits, Kailash Singh, Raul Yhossef Tito Tadeo, Jeroen Raes, Stephanie Humblet-Baron, Adrian Liston, Susan M. Schlenner. Unstable regulatory T cells, enriched for naïve and Nrp1neg cells, are purged after fate challengeScience Immunology, 2021; 6 (61): eabe4723 DOI: 10.1126/sciimmunol.abe4723

Quebecers can get 3rd COVID vaccine ‘at their own risk’ to travel to country that requires it

 Quebec travellers can get a third shot of the COVID-19 vaccine if they are travelling to a destination that requires it, the provincial government says.

The health department announced Saturday that third doses of the mRNA vaccines (Pfizer and Moderna) are available but people who wish to get an additional shot should seek advice and weigh the associated risks.

“This measure is exceptional and the person should be properly counselled to be informed of the potential risks associated with this additional dose, compared to the benefits of the planned trip,” the statement from the health department reads.


The Quebec government says fully vaccinated residents who have received both doses of the Oxford-AstraZeneca COVID-19 vaccine can receive a third dose of an mRNA vaccine.

Quebec says it is offering the extra shot because some countries don’t recognize Covishield, the Oxford-AstraZeneca vaccine made at the Serum Institute of India, and Canadians who have received it could find themselves barred from entry.

Some countries are also currently mulling the recommendation and possible requirement of a third vaccine dose, including France, Britain and Finland.

A spokesman for the Health Department said Monday a third dose doesn’t necessarily provide more protection compared with two doses, adding that the safety of receiving two shots of AstraZeneca mixed with an mRNA vaccine is still unclear.

Officials say the two vaccine doses that the provincial government currently recommends for Quebecers provides “adequate protection.”


There is, however, no international consensus on how many vaccine doses are necessary to limit the spread of the novel coronavirus and its variants.

Virologist Benoit Barbeau describes Quebec’s new policy as morally concerning. He told Global News the third dose won’t increase immunity, only travel eligibility.

According to him, using extra doses for that purpose is not right when other countries are still waiting to vaccinate their population. Barbeau said countries shouldn’t start being picky about which vaccines they prefer.

People that wish to get a third dose can get it at any of Quebec’s walk-in vaccination centres or they can make an appointment on the Clic Santé website.

As of last Thursday, 83 per cent of Quebecers over the age of 12 had received at least one dose of the vaccine and 59.8 per cent were fully vaccinated with two doses, according to Quebec’s public health institute.

https://globalnews.ca/news/8058856/quebec-third-covid-vaccine-travel/

Covid Long-Haulers Get Disability Civil Rights Protections

 Covid-19 survivors with lingering symptoms, who call themselves long haulers, can be protected under the Americans with Disabilities Act, according to guidance put out Monday by the Justice Department and the Department of Health and Human Services.

People with long Covid can have symptoms such as fatigue, difficulty breathing, muscle and joint pain, headaches, depression or anxiety, and difficulty thinking or concentrating, which has become known as “brain fog,” according to the Centers for Disease Control and Prevention.

Long Covid is classified as a disability “if the person’s condition or any of its symptoms is a ‘physical or mental’ impairment that ‘substantially limits’ one or more major life activities,” the guidance said.

Some studies indicate about 10% of Covid-19 patients may become long haulers. Disability rights activists say the Covid-19 pandemic could lead to the largest rise in the number of disabled people in the U.S. in decades.

The announcement was made as President Joe Biden celebrated the 31st anniversary of the landmark disability rights law with lawmakers.

“We’re bringing agencies together to make sure Americans with long Covid who have a disability have access to the rights and resources that are due under the disability law, which includes accommodations and services in the workplace and school and our health-care system so they can live their lives in dignity and get the support they need as they continue to navigate these challenges,” Biden said at the White House.

Some reasonable accommodations for people whose long Covid qualifies as a disability include allowing a person with dizziness to be accompanied by their service animal, providing additional time on a test for a student with difficulty concentrating, and pumping gas for a customer with joint or muscle pain, the guidance said.

Disability rights advocates praised the move by the Biden administration.

“We are glad that the White House recognizes that many COVID long haulers will now be part of the disability community, and therefore are protected under the Americans with Disabilities Act,” Nicole Jorwic, senior director of public policy at the Arc, a nonprofit that advocates for people with intellectual and developmental disabilities, said in an email.

“Guidance from the federal government on COVID as a disability is something that advocates have been asking for,” Jennifer Mathis, director of policy and legal advocacy at the Bazelon Center for Mental Health Law, said in an email.

“COVID has presented important disability rights concerns, including the need for reasonable accommodations and modifications in a variety of contexts, so we were pleased to see the government issue guidance explaining how long COVID may be a disability protected by the Americans with Disabilities Act,” Mathis said.

The CDC released interim guidelines in June to help doctors diagnose and treat long Covid. However, “post-COVID conditions are not yet well understood,” the agency said at that time.

The CDC said it is “challenging” to define long Covid because it is associated “with a spectrum of physical, social, and psychological consequences, as well as functional limitations that can present substantial challenges to patient wellness and quality of life.”

These patients have struggled to get insurance companies to cover their medical treatment and find mental health support after the challenges associated with the disease.

Attorneys expect to see litigation against health insurance companies for failing to pay disability benefits to people with long Covid.

Workplace Accommodations

The ADA requires employers with 15 or more employees to make reasonable accommodations for people with a disability. However, what employers and employees define as reasonable can differ.

blog post published by the Department of Labor earlier this month said that workers experiencing long Covid may be entitled to workplace accommodations under the ADA.

However, the U.S. Equal Employment Opportunity Commission enforces anti-bias laws, including the ADA, in private workplaces, and the agency hasn’t specifically provided guidance on ADA considerations for workers experiencing long Covid. An agency spokesman said the EEOC doesn’t have information on the timing of new guidance on Covid-19, but the agency is monitoring relevant developments.

“We will continue to update the public when we have information that would assist employees and employers with their COVID-related workplace questions,” the spokesman said in an email.

To qualify as having a disability under the ADA, a worker must have, must be regarded as having, or have a record of a condition that substantially limits one or more major life activities, such as caring for oneself, or communicating, or affecting the function of a major bodily function.

The ADA allows workers to sue an employer to allege discrimination or a failure to accommodate a disability.

The Education Department is releasing guidance on how schools may need to modify services for students with long Covid.

https://news.bloomberglaw.com/daily-labor-report/covid-long-haulers-get-disability-civil-rights-protections

‘Mixing and matching’ Covid vaccines over concerns about delta variant

 Dr. Angela Rasmussen, a virologist at Georgetown University, received a booster shot of Pfizer and BioNTech’s Covid-19 vaccine in late June, two months after she got Johnson & Johnson’s single dose.

Rasmussen picked J&J in April, when she was living in Seattle, because she was soon moving to Canada. She was concerned she wouldn’t be able to get the Pfizer vaccine, which requires two doses, due to the supply constraints in Canada at the time. J&J’s vaccine only requires one dose and recipients are considered fully vaccinated two weeks after receiving the shot.

But Rasmussen quickly changed her mind about getting Pfizer’s vaccine once she arrived in Canada. Delta, the highly transmissible variant first found in India that’s now in at least 124 countries, had begun making headlines, and studies at the time suggested a single dose of a Covid vaccine wouldn’t be enough protection.

“Once the supply issues were addressed here in Canada and there really wasn’t a supply shortage of the mRNA vaccines, I decided to go get a Pfizer shot just because I thought that at the very worst, it couldn’t hurt,” she told CNBC in a phone interview.

Some Americans say they are finding ways to get additional doses of the Covid vaccines, with some even going as far as receiving the extra shots from different companies. The thought is that by “mixing and matching” vaccines that use different platforms, people may be able to get broader protection against the coronavirus and its new variants. J&J’s vaccine uses an adenovirus, while Pfizer’s and Moderna’s two-dose vaccines use mRNA technology. It highlights the growing anxiety many Americans have over variants, including delta, already the dominant form of the disease in the U.S.

The practice is nothing new in other parts of the world. Last month, Germany’s government said Chancellor Angela Merkel received Moderna’s shot in June after getting AstraZeneca’s in April. Other countries, such as Italy, are also allowing those under the age of 60 who received a first dose of AstraZeneca’s vaccine to get a different shot when they get their second dose. South Korea said last month it would allow some 760,000 people to get different jabs because of shipment delays there.

Executives from Pfizer, Moderna and J&J have said they expect Americans will need booster shots, and Pfizer has said it plans to ask the FDA to authorize boosters as it sees signs of waning immunity. The Centers for Disease Control and Prevention does not currently recommend Americans mix Covid shots in most circumstances, and federal health officials say booster doses of the vaccines are not needed for otherwise healthy people at this time, although they may recommend it for the elderly or people with compromised immunity.

Since Rasmussen received her booster shot, a new study has suggested the J&J vaccine is much less effective against the delta and lambda variants than against the original virus. The researchers who led the study, which has not yet been peer-reviewed, now say they hope J&J recipients will eventually receive a booster shot of the Pfizer or Moderna vaccines.

To be sure, the new research is at odds with a study from the company, which found the shot is effective against delta, especially against severe disease and hospitalization, even eight months after inoculation. It is likely to reignite the debate of mixing and matching shots in the U.S. as the highly contagious delta variant continues to spread across the U.S.

“I would guess that those who received a single dose of Johnson & Johnson may need a booster of an mRNA vaccine than other people need boosters,” said Dr. Isaac Bogoch, an infectious disease professor at the University of Toronto, who was not involved in either study.

It’s important for scientists and public health officials to be “open-minded” about it, Bogoch said, adding he’s waiting for real-world data to back up the new study.

Israel also released preliminary data last week that showed the Pfizer vaccine is just 39% effective against the virus there, which officials attributed to the rapidly spreading delta variant. Its effectiveness against severe disease and death remained high, the data showed. U.S. and world health officials said they are looking at the Israeli research, which was not peer-reviewed and was scant on details.

The National Institutes of Health began an early stage trial in June looking at mixing and matching Covid vaccines. The trial will include adults who have received one of the three Covid vaccine regimens currently available in the U.S.: J&J, Moderna or Pfizer. Scientists there are trying to determine whether there are any advantages or drawbacks to using different boosters, according to the NIH.

Separate research from the United Kingdom published last month found mixing doses of the AstraZeneca vaccine, which shares similar technology to J&J’s, and an mRNA vaccine produced a stronger immune response against the coronavirus spike protein than just getting two doses of AstraZeneca. The study, called Com-COV, compared mixed two-dose schedules of Pfizer and AstraZeneca vaccines.

Another study, published in Nature Medicine on Monday, found adding the Pfizer or Moderna vaccines as a second dose to J&J led to a better immune response than just two doses of the J&J vaccine and was well tolerated. The vaccinations were performed between Jan. 10 and April 8.

Immunologically, it “makes sense” to follow up one vaccination with another shot that uses a different platform, according to Yale immunologist Akiko Iwasaki.

“The reason for this is because if you’re using a vectored vaccine, like the J&J or AstraZeneca, which use adenovirus, you generate antibodies against the vector so that your second shot with the same vector makes it less likely to induce a robust immune response,” she said.

Aside from Covid, mixing and matching vaccines that use different platforms is not something unusual, Iwasaki said. Looking at vaccine studies and trials for HIV, it’s “almost standard that people use different platforms to prime and boost,” she said.

Mixing vaccines may prevent the body from causing a sort of “mediated clearance of the vaccine itself,” where the shot is less effective, Iwasaki said.

“The spike protein that is used for the J&J and Moderna and Pfizer vaccines are virtually identical, so it is not like you’re getting cross-reactive protection against different variants,” she said. “But if you generate much higher levels of neutralizing antibodies, it will find epitopes in the variant that can also protect against the variant.”

Mixing the Covid vaccines appears to be safe but at the same time “we don’t know what we don’t know,” according to Dr. Dan Barouch, an immunologist at Harvard Medical School who helped develop the J&J vaccine.

“There’s limited data on the safety or efficacy of the approach, but theoretically, there is no reason that I can see that raises major safety concerns,” Barouch said. “But there are theoretical benefits in terms of the immune responses and potential improvement of efficacy.”

The World Health Organization’s chief scientist, Dr. Soumya Swaminathan, recently advised individuals against mixing and matching Covid vaccines from different manufacturers, saying the practice is a “data-free zone” and immunogenicity and safety both still need to be evaluated further.

“It’s a little bit of a dangerous trend here,” Swaminathan said during an online WHO briefing on July 13.

Still, some doctors are already suggesting immunosuppressed populations, such as patients living with cancer or those who have had organ transplants, might benefit from an extra dose of the same or another Covid vaccine, Barouch said.

A CDC advisory group on Thursday considered whether fully vaccinated Americans with weakened immune systems need a booster dose of a Covid vaccine after data shows they are less likely to have antibodies to fight the disease and more likely to suffer from a so-called breakthrough infection.

“The hardest to vaccinate people are those who are immunosuppressed,” Barouch said, adding early data shows the approach of mixing and matching vaccines may be safe and effective for those populations.

Rasmussen, the virologist at Georgetown University, said she didn’t experience any safety concerns or side effects, besides a sore arm, after getting a booster of Pfizer’s vaccine.

Matthew, a retired photographer from Los Angles, also said he didn’t experience any bad side effects after receiving a booster shot. Similar to Rasmussen, Matthew received a single dose of Pfizer’s vaccine several weeks after getting a single dose of J&J.

He said he decided to get a booster shot because he worried about his level of protection against variants. After speaking with his doctor about mixing and matching inoculations, Matthew concluded it was safe to get his second shot from Pfizer.

“When I got Johnson & Johnson I was tired for maybe a couple of days and I had intense pain in my calves for almost 48 hours,” said Matthew, 70, who asked that his last name not be used to protect his privacy. “I felt fine after the second dose.”

Dr. Paul Offit, who advises the FDA on Covid vaccines, said the CDC should provide “more direction” and create guidelines for how providers should be thinking about mixing and matching vaccines. Though he said he doesn’t expect the CDC to endorse the practice until there is more data and the U.S. studies are complete.

“It would be helpful to have some guidelines from the CDC on how to think about this,” he said. “More importantly, it would be helpful to have studies that are in hand, that are perfectly done that we can actually answer some of these questions.”

Likewise, Barouch said he doesn’t expect any new recommendations until there is more data.

“There’s going to be a lot of data soon and then there will be data-driven recommendations,” he said.

https://www.cnbc.com/2021/07/26/delta-people-are-mixing-and-matching-covid-vaccines-over-concerns-about-variant.html