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Monday, December 7, 2020

Ash 2020 – US academics target the Car-T relapse problem

 Lack of persistence remains a problem for BCMA-targeted Car-T therapy, but the US NCI reckons it has an answer. The group is working on FHVH-BCMA-T, a construct that uses as the binding region a heavy chain antibody domain, which is smaller and simpler that the usual ScFv domain that most others use. At Ash Dr Lekha Mikkilineni reported an impressive 90% overall remission rate in 20 multiple myeloma subjects across all five FHVH-BCMA-T doses, of which the fourth, six million cells/kg, was determined to have the best mix of efficacy and safety. Dr Mikkilineni said FHVH-BCMA-T could avoid unwanted immune system responses against linkers and ScFv junctions, because heavy chains do not have any, and the fact that a fully human binder is used could further reduce alloreactivity and cut relapse while cells continue to express BCMA. Nevertheless, only 10 of the 18 remissions are ongoing, patients presumably relapsing because of loss of the BCMA antigen. The lack of durability problem is far from solved.

Over Half of FDNY Firefighters Won't Get Vaccinated: Union Poll

More than half of the FDNY firefighters who answered an internal survey said they won't take the coronavirus vaccine once it becomes available to first responders in a couple of weeks, the union representing New York City's firefighters said over the weekend.

Uniformed Firefighters Association President Andrew Ansbro said of the 2,053 firefighters surveyed in recent days, roughly 55 percent said they would not get the vaccine. Ansbro believes a large number of the firefighters resistant to the vaccine share concerns of trying a new vaccine or have limited information of its effectiveness.

"You also have to keep in mind that 35 percent of New York City firefighters have been infected and have overcome the virus. A lot of these members feel that they have antibodies and are not an at-risk category," Ansbro said at a press conference Sunday.

The surveyed firefighters represent approximately a quarter of the union's overall membership.

An internal FDNY memo obtained by NBC News last week told firefighters to prepare for the first vaccine in a matter of weeks.

The memo, issued by Commissioner Daniel Nigro and the Chief of Department stresses that the vaccine either from Moderna or Pfizer will “NOT” be mandatory “but the Department recommends that members consider the overall health benefits.”

"As a union we are encouraging our members to get the vaccine but we are defending their right to make that choice," Ansbro said. "I personally feel this vaccine is safe, I've done my own research, I will be getting the vaccine and I will be encouraging other members to do so. In the end, it is their own personal choice."

The FDNY, particularly the paramedics and EMTs, were particularly hard hit by the virus this spring with as many as 1 in 4 medics out sick during the height of the pandemic (so far) in NYC.

The Department also handled a record 6,500+ 911 calls for nearly a week as hospitalizations and deaths from COVID-19 exploded citywide.

https://www.nbcnewyork.com/news/coronavirus/more-than-half-of-fdny-firefighters-wont-get-vaccinated-union-poll-suggests/2764027/

Cyclosporine A plus low-dose steroid in moderate to severe COVID-19 improves outcomes

 Jose Luis Galvez-Romero 1Oscar Palmeros-Rojas 2Fernando Antonio Real-Ramírez 3Saúl Sánchez-Romero 3Ramiro Tome-Maxil 3María Patricia Ramírez-Sandoval 3Rosaura Olivos-Rodríguez 3Salvador Eduardo Flores-Encarnación 3Ana América Cabrera-Estrada 3José Ávila-Morales 3Víctor Cortés-Sánchez 3Gonzalo Sarmiento-Padilla 3Sandra Elizabeth Tezmol-Ramírez 3David Aparicio-Hernández 3Mario Iván Urbina-Sánchez 3Miguel Ángel Gómez-Pluma 3Surizadith Cisneros-Méndez 3Dinorah Ivonne Rodríguez-Rivas 4Sergio Reyes-Inurrigarro 5Gilberto Cortés-Díaz 5Carlos Cruz-Delgado 5Jaqueline Navarro-González 6José Deveaux-Homs 7Sigifredo Pedraza-Sánchez 8



  • DOI: 
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    Abstract

    Background: COVID-19 pandemic causes high global morbidity and mortality, and better medical treatments to reduce mortality are needed.

    Objective: To determine the added benefit of Cyclosporine-A (CsA), to low-dose steroid treatment, in patients with COVID-19.

    Methods: Open-label, non-randomized pilot study of patients with confirmed infection of SARS-CoV2, hospitalized from April to May 2020 at a single center in Puebla, Mexico. Comparative treatment with steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days.

    Results: 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ±13.3; 69% men), and 104 steroids alone (age 54.06 ±13.8; 61% men). All patients received clarithromycin, enoxaparin, and methylprednisolone or prednisone up to 10 days. Patient´s death was associated with hypertension (RR=3.5) and diabetes (RR=2.3). Mortality was 22 and 35% for CsA and control groups (p=0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (p=0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, p=0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, p=0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, p=0.0003) for all patients.

    Conclusion: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

    https://pubmed.ncbi.nlm.nih.gov/33274479/                  

    Despite Biden pledge, coronavirus bill in Congress now may be all Americans get

     President-elect Joe Biden has called the $908 billion coronavirus aid bill taking shape in Congress a “downpayment” toward a bigger stimulus next year, but if it passes, that is all U.S. businesses and workers should count on, economists and political analysts say.

    There is likely to be little appetite among Republicans for supporting a second round of $1 trillion-plus spending after Biden takes office on Jan. 20 - a task that would be made more difficult if Republicans retain control of the Senate in Jan. 5 runoff elections in Georgia - said John Lieber, managing director of the Eurasia Group political risk consultancy.

    “If they do the full bipartisan $900 billion, then I think it’s a big ask to do anything new after Biden takes office,” said Lieber, a former adviser to Senate Majority Leader Mitch McConnell.

    Additional stimulus “would only become possible in a downside scenario where the vaccine rollout doesn’t go smoothly and the economy continues to drag well into 2021, leading to serious strains” on households, small businesses and local governments,” Lieber said.

    And even if Democrats take the Georgia seats, they would achieve a majority only with a tie-break vote from Vice President-elect Kamala Harris, leaving them far short of the 60 votes needed for most major spending legislation outside of normal budget reconciliation rules.

    Congressional leaders had hoped to unveil a near-term coronavirus aid package based on a $908 billion bipartisan proposal as early as Monday. Negotiations are hung up on differences over aid to state and local governments and COVID-19 liability protections for businesses.

    Moody’s Analytics Chief Economist Mark Zandi said members of Congress were under pressure to pass a stimulus bill now “because if they don’t, the economy is going to evaporate and that will be too much to bear politically.”

    He added that his baseline outlook for the economy assumes that Congress will pass “little of consequence” to stimulate economic growth after Biden takes office. As a result, it will take three full years - until the end of 2023 - to recover all of the jobs lost during the pandemic this year.

    By contrast, it took eight years to recover the jobs lost from the 2008-2009 Great Recession, another situation where Congress prematurely withdrew fiscal support, he said.

    Annual federal deficits had nearly doubled to the $1 trillion range during President Donald Trump’s term before the pandemic hit. After passing over $2 trillion in coronavirus-related stimulus earlier this year, a pivot back to fiscal restraint is “already starting to happen here in the middle of the pandemic,” Zandi said.

    Widespread distribution of the coronavirus vaccines is expected next spring, making Republican lawmakers reluctant to support another round of stimulus, said Michael Strain, director of economic policy studies at the American Enterprise Institute, a pro-business conservative think tank in Washington.

    Many will want to wait and see if the vaccine works and the economy starts to recover. In addition, Republicans, even if they lose control of the Senate, will be reluctant to give Biden an early victory, he said.

    "I expect that there will be difficulty in passing another economic stimulus measure in February," Strain told a Brookings Institution forum here last week. Democrats who hold out for a better deal after Biden takes office are likely making a "significant mistake."

    https://www.reuters.com/article/usa-economy-coronavirus-stimulus/despite-biden-pledge-coronavirus-bill-in-congress-now-may-be-all-americans-get-analysts-idUSL1N2IN1S5

    Moderna, Pfizer CEOs Skip White House COVID Vaccine Summit After Leaking Data To Biden

     Despite repeatedly pledging to be apolitical, Pfizer and Moderna have been criticized for waiting to release their 'Phase 3' trial data until just days after the Nov. 3 vote, while shooting down Trump's insistence that a vaccines would be approved in a matter of weeks as extreme hyperbole, if not an outright lie.

    More than a month later, Pfizer and Moderna have revealed that they remain in close contact with the Biden team. As it turns out, Biden may have been briefed on the initial Pfizer and Moderna data before President Trump, even though, at that point, Biden's victory had been decided by the media, and the media alone, STAT News reports.

    Now, both Pfizer and Moderna are skipping a White House vaccine summit, despite taking billions in taxpayer dollars for their vaccines. Unlike Moderna, which benefited directly from "Operation Warp Speed" funds, Pfizer self-financed the development of the vaccine, before striking a deal with OWS to supply the US with millions of doses.

    Both companies, and their executives, have benefited from these Trump Administration programs. But now, it seems, they're trying to send a message to the public: The Trump Administration doesn't deserve credit for the vaccines.

    The summit, first reported last week, has been derided by the Administration's critics as a PR stunt intended to try and 'take credit' for rolling out COVID-19 vaccines.

    It's not the first time that Pfizer, in particular, has tried to distance itself from Operation Warp Speed. Back on Nov. 10, Kathrin Jansen, a Pfizer executive, attempted to distance the company from OWS by insisting Pfizer had never taken any money from it, a line the company has continued to repeat, despite striking the deal noted above. It sure is a lot easier to bootstrap vaccine development when you're a resource-rich pharma giant like Pfizer, and you know you can fall back on $1.95BN from the federal government right out the gate.

    Other companies involved in vaccine distribution logistics, but not in vaccine development itself, are still expected to attend, including FedEx, UPS, CVS, Walgreens, and McKesson. Though most will likely send lower-ranking executives as opposed to their CEOs.

    Additionally, Peter Marks, the FDA official in charge of overseeing vaccine approvals, might attend, though the FDA is reportedly "uneasy" about the political connotations.

    And the Democrats complain that Trump has been "sabotaging" the transition - yet, executives tacitly aligned with his political opponents won't even deign to meet with the president and his team.

    https://www.zerohedge.com/markets/moderna-pfizer-ceos-skip-white-house-covid-vaccine-summit-after-leaking-data-biden

    China Spreads Misinformation On COVID Origins As WHO Probe Lingers

     Something strange is going on at the New York Times, in that the paper all of a sudden seems keen on digging hard into the truth about the origins about Covid-19. In fact, as of last week, CNN appears to be doing the same. 

    This weekend the Times published a lengthy piece that looked into how China is peddling different stories to try and cover up the origins of the Covid pandemic. These efforts come as the World Health Organization readies an investigation into how the virus jumped from animals to humans. 

    In addition to reporting on China's misinformation, the piece also seemed to lend credence to the idea that the "official narrative" out of China (that got us banned from Twitter for some time) may not be the gospel the mainstream media once thought it was.

    The NYT refutes deflections from China, where officials are now blaming everybody but themselves as the culprit for Covid. The article noted that "state news media has published false stories misrepresenting foreign experts" in order to suggest the virus came from outside of China. 

    One non-peer reviewed paper from the state run Chinese Academy of Sciences suggested that India could be to blame. It states: “Wuhan is not the place where human-to-human SARS-CoV-2 transmission first happened.” The paper was submitted to, and then mysteriously pulled by its authors from The Lancet. 

    The country is also pushing a narrative that frozen food from other countries could have started the pandemic. Wu Zunyou, the chief epidemiologist at the Chinese Center for Disease Control and Prevention said recently: “More and more evidence suggests that the frozen seafood or meat products probably spread the virus from countries with the epidemic into our country.”

    But experts have said "packaged food alone cannot explain why the first major outbreak took place in Wuhan."

    Erin Baggott Carter, an assistant professor of political science at the University of Southern California, said the misinformation is to try and skirt blame, plain and simple. She said: “If Xi is able to escape blame for the coronavirus, that reduces one major source of discontent with his rule.”

    The ramp up of misinformation comes as the World Health Organization (WHO) is starting an investigation into Covid's origins. China has "tightly controlled" the WHO's efforts in the past, the NYT notes:

    The party also appears eager to muddy the waters as the World Health Organization begins an investigation into the question of how the virus jumped from animals to humans, a critical inquiry that experts say is the best hope to avoid another pandemic. China, which has greatly expanded its influence in the W.H.O. in recent years, has tightly controlled the effort by designating Chinese scientists to lead key parts of the investigation.

    WHO emergency director Michael Ryan said: “We need to start where we found the first cases and that is in Wuhan in China.”

    Recall, about 10 months after Zero Hedge was suspended from Twitter and ridiculed by those peddling the "official" narrative about Covid-19 for an article we published asking critical questions about the origins of the coronavirus pandemic, the Washington Post also did the same thing.

    As a reminder, in January 2020, shortly after we asked if "This [Is] The Man Behind The Global Coronavirus Pandemic", referring to Wuhan Institute Of Virology scientist Peng Zhou (who three months later was being investigated by western spy agencies for his role in creating Covid) and some low-grade "reporter" from Buzzfeed decided to report us to Twitter for "doxxing" Zhou using publicly available information, Twitter told us our account had been suspended.

    Recall, in September 2020, Twitter also nuked the account of "rogue" Chinese virologist, Dr. Li-Meng Yan, who "shocked" the world of establishment scientists and other China sycophants, by publishing a "smoking gun" scientific paper demonstrating that the Covid-19 virus was manmade.

    It was not immediately clear what justification Twitter had to suspend the scientist who, to the best of our knowledge, had just 4 tweets - none of which violated any stated Twitter policies - and the only relevant tweet being a link to her scientific paper co-written with three other Chinese scientists titled "Unusual Features of the SARS-CoV-2 Genome Suggesting Sophisticated Laboratory Modification Rather Than Natural Evolution and Delineation of Its Probable Synthetic Route" which laid out why the Wuhan Institute of Virology had created the covid-19 virus.

    For those who missed it, here is our post breaking down Dr. Yan's various allegations which twitter saw fit to immediately censor instead of allowing a healthy debate to emerge.

    133 days after Twitter "permanently" banned Zero Hedge on January 31, the network reinstated us after admitting it made an error. 167 days after that, the Washington Post asked the questions that got us banned in the first place. Now, 309 days since our initial "permanent" ban, it appears The New York Times isn't sold on the official narrative either. 

    Of course, there are numerous theories as to why the NYT cares so much all of a sudden.

    ...but regardless of whether or not the mainstream media embraces it - and, if they do, regardless of for what reason - the truth will eventually make its way out.

    https://www.zerohedge.com/geopolitical/china-spreading-misinformation-about-covids-origins-who-investigation-lingers

    Bluebird bio reports group in LentiGlobin study had no severe VOEs

     

    • Bluebird bio (NASDAQ:BLUE) says new data from group C of its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin gene therapy for adults and adolescents patients with sickle cell disease show a complete elimination of severe vaso-occlusive events and VOEs between six and 24 months of follow-up.
    • Also reports positive patient-reported quality of life outcomes assessed with validated PROMIS-57 demonstrate clinically meaningful reductions in pain intensity at month 12 post-LentiGlobin for SCD treatment.
    • "Now with more than two years of data, we continue to observe promising results in our studies of LentiGlobin for SCD that further illustrate its potential to eliminate the symptoms and devastating complications of sickle cell disease," said bluebird bio Chief Medical Officer David Davidson, MD. "In addition to these clinical outcomes, for the first time with a gene therapy we now have patient-reported outcomes through the validated PROMIS-57 tool, showing reduction in pain intensity at 12 months after treatment with LentiGlobin for SCD."
    • Nineteen patients treated in group C had a history of severe VOEs, defined as at least four severe VOEs in the 24 months prior to informed consent (annualized rate of severe VOE min-max: 2.0 – 10.5 events) and at least six months follow-up after treatment with LentiGlobin for SCD.
    • There have been no reports of severe VOEs in these group C patients following treatment with LentiGlobin for SCD. In addition, all 19 patients had a complete resolution of VOEs after month 6.
    • https://seekingalpha.com/news/3642313-bluebird-bio-reports-group-in-lentiglobin-study-no-severe-voes