Moderna's COVID vaccine scheduled for FDA review on Dec. 17

 

• Moderna (NASDAQ:MRNA) +6.9% post-market after soaring to another all-time high in today's trade, as the company asked U.S. and European health regulators to authorize use of its COVID-19 vaccine, which was shown to be 94.1% effective - with 100% efficacy in preventing severe COVID - in a full analysis of a pivotal study.
• A panel of outside experts advising the U.S. Food and Drug Administration will meet Dec. 17 to review the evidence for Moderna's vaccine and vote on whether to recommend that the agency authorize its emergency use; a similar meeting has been set for Dec. 10 for the Pfizer-BioNTech vaccine.
• It is unclear how long the FDA will take to make a decision on allowing use, but Moderna CEO Stéphane Bancel says it is possible the agency could decide within a few days of the advisory panel meeting, or between Dec. 18-20.
• Both vaccines have shown more than 90% efficacy, and mRNA-1273's less-rigorous distribution and shipping requirements give the Moderna drug a slight edge, though both will be used given current production constraints.
• Moderna's market value has now reached a record $60B, topping pharma heavyweights such as Vertex and Regeneron, even though it has yet to bring a drug to market.
• https://seekingalpha.com/news/3640180-modernas-covid-vaccine-scheduled-for-fda-review-on-dec-17

Release of immature blood cells from bone marrow signature of severe COVID-19

 In severe cases of COVID-19 disease, not only classic immune cells play a role. In particular, the release of immature precursor cells from the bone marrow into the blood indicates a particularly severe course of the disease and could contribute to complications. This has been shown by an international research team involving the DFG Cluster of Excellence "Precision Medicine in Chronic Inflammation" (PMI). The team included physicians and researchers from Kiel University (CAU), the University Medical Center Schleswig-Holstein (UKSH) and the Universities of Bonn, Cologne, Luebeck, Tuebingen and Nijmegen as well as the Research Center Borstel—Leibniz Lung Center and the German Centre for Neurodegenerative Disorders (DZNE), together with colleagues from the national DFG research association DeCOI. The findings have been published in the journal Immunity on Thursday, November 26th.

In search of a biomarker for a severe COVID-19 course

Infections with the novel coronavirus SARS-CoV2 may result in highly heterogeneous clinical pictures. While many of the infections are mild or even asymptomatic, the disease can become life-threatening, especially in older people. In these severe cases, other organs such as the heart or kidneys can be affected in addition to the lung. A immunological misfiring plays an important role, but findings are accumulating that damage to small blood vessels and over-activated blood clotting are decisive factors for a severe course. One of the most common direct causes of death from COVID-19 is blood clots in the lungs.

"Despite numerous studies, we actually know relatively little about the course of the disease over time. Which cell types play an important role here and when? And can we identify early molecular signatures in the blood that point to severe course of the disease later on? These were questions we asked ourselves at the beginning and we got surprising answers," explains one of the lead authors of the study, Professor Philip Rosenstiel, Director of the Institute for Clinical Molecular Biology (IKMB) at the CAU and the UKSH and member of the steering committee of the Cluster of Excellence PMI.

Two immature blood cell types characteristic of severe course

The team examined blood samples from COVID-19 patients who were hospitalized at the university hospitals in Kiel, Bonn, Cologne and Nijmegen. In a group of 14 patients, circulating blood cells were analyzed in a time series. Blood samples from healthy people were used as a comparison. " The special feature is that we were able to analyze hundreds of thousands of cells in parallel with the help of so-called single cell genomics and were thus able to identify rare cell types," explains Dr. Joana Pimenta Bernardes, young scientist of the Cluster of Excellence PMI and postdoc at the IKMB, who is one of the first authors of the study together with the other two young researchers Dr. Florian Tran, Clinician Scientist of the Cluster of Excellence PMI, and Dr. Neha Mishra. Mishra, who is also researching at the IKMB as a postdoc, explains further: "Together with other data such as clinical laboratory values and measurements of inflammatory messengers, we were able to create a kind of fingerprint, a signature, of the altered functioning of these cells and track it over time."

Signatures of two immature cell types are therefore particularly characteristic of severe COVID-19 disease: platelet precursor cells, so-called megakaryocytes, and immature red blood cells. "This is particularly surprising because these precursor cells are normally not in the blood but in the bone marrow, where they mature as needed," explains Tran. "We know of such progenitor cells being washed out into the blood of seriously ill patients, for example in bacterial sepsis (blood poisoning). This has not yet been described for COVID-19," Tran continues.

"With the help of high-precision cellular genomic analyses, we were able to draw a very detailed picture of the cellular changes throughout the course of the disease. While previously we mainly looked at immune cells, we were now able to find cell types that had previously been overlooked," says Joachim Schultze, professor at the University of Bonn and research group leader at the DZNE, one of the last authors of the study.

Possible explanation for coagulation problems with COVID-19 found

The scientists gained important insights from a group of 39 COVID-19 patients who had been treated in the intensive care unit in Nijmegen, i.e. had particularly severe courses of disease. In this group of patients, a signature of the megakaryocytes and red blood cell progenitor cells was particularly strong in patients who died of the disease compared to patients who recovered. "The megakaryocytes reflect a well-known COVID-19 problem: blood platelets are responsible for blood coagulation. One of the most common direct causes of death from COVID-19 is coagulation problems. The emergency-activated megakaryocytes in the blood may produce platelets that aggregate more easily and thus lead to the coagulation problems," assumes Rosenstiel . The increase in red blood cell progenitor cells indicates a lack of oxygen and is known as an emergency reaction in severe lung diseases.

Together to success

The study has been made possible by the nationwide consortium—the "German COVID-19 OMICS Initiative" (DeCOI) - and was carried out in cooperation with partners from the "Human Cell Atlas," an international consortium for single cell analysis. "It was only through this teamwork that the complex analyses and interpretation of the data could be mastered in the short time available," says Schultze, who is also the coordinator of the DeCOI consortium.

"With the present work, we have now created the basis for validating novel biomarkers at an early stage of COVID-19 disease to identify patients at risk for a severe course of the disease. This would enable us to improve the care of particularly severely affected patients even more specifically," says Professor Stefan Schreiber, Director of the Clinic for Internal Medicine I, UKSH, Campus Kiel, Director at the IKMB and spokesperson of the Cluster of Excellence PMI. "I am particularly pleased that three young researchers from the PMI Cluster of Excellence have been significantly involved in this work as lead authors, including one of our Clinician Scientists. This shows how the young researchers in the cluster are already doing excellent research with relevance for society."

More information: Joana P. Bernardes et al. Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells and plasmablasts as hallmarks of severe COVID-19 trajectories, Immunity (2020). DOI: 10.1016/j.immuni.2020.11.017

https://medicalxpress.com/news/2020-11-immature-blood-cells-bone-marrow.html

Pandemic to delay cancer advances nearly 18 months, researchers fear

 Cancer researchers fear advances for patients could be delayed by almost a year and a half because of the effects of the COVID-19 pandemic, a new survey reveals.

Scientists at The Institute of Cancer Research, London, told the survey that their own research advances would be pushed back by an average of six months by the initial lockdown, subsequent restrictions on laboratory capacity and the closure of national scientific facilities.

With broader effects on charity funding, disruption of collaboration and personal interaction between scientists, and diversion of research efforts to COVID-19, the respondents estimated that major advances in cancer research would be delayed by an average of 17 months.

But the researchers said science had now adapted in many ways to the pandemic and that long-lasting damage to cancer research could be mitigated through extra funding from charitable donations or Government support—calling for investment in staffing, new technology such as robotics and computing power.

Making up for lost time

The Institute of Cancer Research (ICR), which has discovered more cancer drugs than any other academic center in the world, has like many research organizations been hit by cuts to its own fundraising income and to grants from other charities. The ICR had to pause much of its work during the initial lockdown, and is now running a major fundraising appeal to help kick-start its research and make up for lost time.

The ICR surveyed 239 of its researchers in order to detail the impact the pandemic has had on its research and to point towards ways of moving research forward again as quickly as possible.

Respondents said they had lost an average of 10 weeks of research time to the first lockdown itself, and that their own scientific advances would be pushed back by an average of six months. Almost all said COVID-19 had had an impact on their work—with 36 percent saying it had had a 'moderate' impact, another 36 percent a 'substantial' impact and 5 percent an 'extreme' impact.

Some 91 percent said the biggest problem had been the closure of labs during lockdown and subsequent restrictions in access to facilities and equipment—citing, for example, closure of major, national research facilities. The average ICR researcher spent 53 percent of their working time in a lab before lockdown, plummeting to 5 percent during lockdown and since recovering to 34 percent.

The next most cited impacts were inability to enroll patients on clinical trials (60 percent), to access clinical samples (46 percent) or to interact in person with colleagues (41 percent) – with video conferencing seen as a poor substitute for meeting in person at conferences and other events.

Keeping labs open to prevent further disruption

Many researchers were, however, able to use the time productively—for example through doing training (48 percent), or carrying out desk-based (62 percent) or computational (33 percent) research. Some carried out research into COVID-19 (5 percent), including studies that have given us greater insight into the effects of COVID-19 on cancer treatment pathways.

But the survey nevertheless laid bare the emotional impact of the pandemic on researchers. Some 69 percent of researchers said the impact of the pandemic on their work had left them 'frustrated," 39 percent had been 'saddened' and 25 percent 'depressed."

The respondents were strongly supportive of efforts to keep labs open to prevent any further disruption to research advances for cancer patients. The ICR's labs have managed to stay open during the second lockdown period while taking significant measures to help prevent risk of spread.

The ICR's researchers did feel that science had adapted to COVID-19 and that there were various ways to make up for lost time—over 60 percent felt funding for extra staff time would help; almost 40 percent wanted upgrades in technology, for example for robotics, and 29 percent increased computing power.

Inspiring to see how researchers have adapted

Professor Paul Workman, chief executive of The Institute of Cancer Research, London, said:

"Our researchers are passionate about making advances to benefit patients, so it has been hugely frustrating that their work has been so disrupted, although also inspiring to see how well they have adapted to the restrictions the pandemic has imposed on our lives.

"It is sobering to see that our researchers are estimating that their own research advances will be delayed by six months—and that the wider impact, because of the interconnectedness of science, is likely to push back major advances for patients by nearly a year and a half.

"Our survey though does provide solutions to mitigate the impact—in the form of investment in staffing, new technologies and computing power. For that, we need more of the generous donations we have been receiving to our emergency appeal, along with a commitment from the Government to help fill the funding gap for the life sciences left by the pandemic."

Impossible to replace the light bulb moments from being together

Dr. Sebastian Guettler, deputy head of structural biology at The Institute of Cancer Research, London, said:

"Our work is reliant on access to shared infrastucture in London and nationally, and during the first lockdown this became impossible. These facilities have now introduced or widened remote access—we can control experiments hundreds of miles away from our own homes, with good broadband internet speeds. But we continue to be limited when it comes to preparing samples in the lab, which are then shipped to these facilities for experiments. It's been an intensely frustrating time, and some teams are much more affected than others—depending on which facilities they need.

"The coronavirus has also reduced or stopped the spontaneous interactions with colleagues that science is so dependent on for generating new ideas. Video conferencing has helped us stay connected as a lab and a community, but it's not a true replacement for those light bulb moments you might get from chatting with someone at a conference or over coffee in the canteen.

"There are some positives from this period. Being able to access shared facilities remotely will be helpful in the future, and we know we can make up for some of the lost time if we have more funding for people and equipment to catch up on the lost laboratory work."

Improving clinical research after COVID

Professor Emma Hall, deputy director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, said:

"Our work relies on new clinical trials starting up and existing ones continuing to happen—and COVID-19 has made that incredibly challenging. The pandemic has meant that it will take longer to answer the questions asked in our trials, and that will delay new treatments getting to patients.

"During the initial lockdown, non-COVID clinical research pretty much shut down within the NHS. A lot of our trials were effectively paused because the hospitals that host them had to redeploy resources to COVID-19 research or treatment.

"COVID-19 has forced some changes in how we work that are for the better though. We can capture and manage data remotely rather than relying on paper. The COVID-19 trials have also shown how research can benefit from easier access to routine medical data—hopefully this will be translated to other clinical research and mean more streamlined, simpler to run trials.

"I hope we can use this experience to benefit cancer patients in the long term, but that will only be possible with more support or future advances will be delayed."

The impact of the pandemic on patients

Mother of two Sally Steadman-South, from Sheffield, is living with stage 4 melanoma. She was first diagnosed in 2014 at the age 35, after having a mole removed on her chest. Despite trying numerous treatments including surgery, radiotherapy and immunotherapy, the cancer continued to spread.

For the last two years she has been on the targeted drugs, dabrafenib—a treatment underpinned by the ICR's science—and trametinib, and currently has no evidence of disease.

This year Sally celebrated her 40th birthday with her family—a milestone she never thought she would reach.

Sally shared her concerns about the impact of COVID-19 on cancer patients:

"The coronavirus has been especially devastating for many cancer patients—I have been lucky my treatment has been unaffected but we know many have not and their care has been affected. It's also clear that future research advances have also been delayed.

"I feel lucky that my treatment has worked well so far but I know that the cancer could become resistant to the drugs at any time. When you get a diagnosis like mine it changes what time means to you—maybe this pandemic has made many more people value and appreciate quality time with family and loved ones. I want to be around for school plays and sports days, see my daughter go to secondary school and see my son enjoy his time there too and start planning his own future.

"We recently went to pick our Christmas tree and they are planting fields of new trees which will be ready in 2028. We agreed that this would be our new goal. I would be there to see this new field of Christmas trees and we would go as a family to pick one. We need to make up for the time lost to this virus so people like me can live longer and make important memories like these."

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Explore further

Nearly one in five cancer patients less likely to enroll in clinical trials during pandemic

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https://medicalxpress.com/news/2020-11-pandemic-cancer-advances-months.html

To prevent Alzheimer's, edit key gene in human nerve cells?

 A team of researchers at Laval University has found evidence that it might be possible to the chances of developing Alzheimer's disease by editing a key gene in nerve cells. In their paper uploaded to the bioRxiv preprint server, the group describes experiments they conducted that involved editing genes and what they learned from them.

Prior research has shown that one of the factors involved in the development of Alzheimer's disease is a buildup of beta-amyloid—a type of protein—on brain cells. Prior research has also shown that some people have a gene variant called A673T—those who express it are four times less likely than the general populace to develop Alzheimer's disease. In this new effort, the researchers looked into the possibility of editing human brain cells to give people the gene variant A673T and thereby reduce their chances of developing Alzheimer's disease.

The team noted that the A673T mutation differs from its cognate in those who do not express it by a single DNA letter, suggesting it might be relatively easy to add the mutation. They next tried editing brain cells using a CRISPR technique. And while that attempt proved relatively successful, other aspects of the technique drove the researchers to try another—prime editing. This relatively new technique allows for directly converting one base letter to another. Using this technique, the researchers found that they were able to edit approximately 40% of the brain cells in vitro. They note that such an amount is likely not high enough to prevent buildup of beta-amyloid, and thus not enough to slow the onset of Alzheimer's disease. But more research might lead to better results.

The researchers also note that such editing of brain cells in humans would require early diagnosis because by the time symptoms present, it might be too late to conduct gene editing to prevent the buildup of beta-amyloid. They note that future efforts might instead involve editing the DNA of only those who are deemed at risk of developing the disease while they are still young.

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Explore further

Uncovering potential pathway to slowing Alzheimer's

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More information: Antoine Guyon et al. Base editing strategy allows insertion of the A673T mutation in APP gene to prevent the development of Alzheimer's disease, bioRxiv (2020). DOI: 10.1101/2020.10.27.357830

https://medicalxpress.com/news/2020-11-alzheimer-disease-key-gene-human.html

Docs Can Prescribe Opioids Via Telemedicine, for Now

 In the COVID-19 era, under relaxed federal emergency orders, licensed clinicians have been able to prescribe opioid analgesics for their patients even if they've only ever seen the patient via telehealth, rather than in person.

For providers like Stephen Bekanich, MD, a palliative care physician for Ascension Texas in Austin, this provision allows him to help seriously ill patients without requiring in-person visits that may be difficult for them or could expose them or their caregivers to the virus.

Still, he worries, given ongoing national concerns about prescription drug overdoses, that this privilege might be on shaky ground, although he is not aware of opioid prescribers being targeted by regulators during the current crisis.

But what happens when the current COVID emergency order issued by the Department of Health and Human Services (HHS) expires? Palliative care doctors who have learned how to manage patients remotely via telemedicine may have to return to old ways -- including a requirement that they see a patient in person before prescribing opioids.

The Prescribing Situation

The Ryan Haight Online Pharmacy Consumer Protection Act, passed in 2008, included a prohibition on writing prescriptions for controlled substances such as opioids by means of the internet unless the clinician first conducted an in-person exam. It came with a number of exceptions and carve-outs, one of which is for public health emergencies such as the one declared by HHS Secretary Alex Azar, MD, on Jan. 31. It effectively put the Ryan Haight Act provision on hold for the duration of the emergency.

The Drug Enforcement Agency issued an exception allowing prescribing of controlled substances via telemedicine without a prior in-person visit during the pandemic, though it specifies that telephone-only communications are not part of that exception.

CMS has indicated that it will revisit guidelines around telehealth services generally at the time when the emergency order is phased out, Bekanich noted. "But will it address the prescribing situation?"

This question plays out in the context of the other, ongoing national epidemic of prescription opioid overdoses, with federal agencies trying to curb excessive opioid prescribing, said attorney Sarah Churchill Llamas, chair of the healthcare industry group at the law firm Winstead PC in Austin.

"Doctors in general are concerned about prescribing opioids," she said. The Texas Medical Board has rules for how to establish the patient-doctor relationship, and it should still meet the same standard of care whether virtually or in person. For some regulators, it's an ongoing question whether it's even possible to establish a professional relationship with a patient via telemedicine.

Because every state is different, both for opioids and telehealth, Llamas encourages providers to take a close look at existing state law. Patients receiving hospice or palliative care and those with cancer may be treated differently in the regulations, but that is no guarantee the prescribing physician won't draw regulatory scrutiny, she added. For those who want to practice across state lines, it's even more complex.

"At the end of the day, even if doctors do everything they're supposed to, they could still get reviewed by their state medical board. Now that you're overlaying telemedicine on top of opioid prescribing, I could see where a physician might say: 'I just don't feel comfortable going out on a limb with this,'" she said. "My advice, do what's best for your patients' care, but plan for the future. You have to know that the relaxation of regulations due to the emergency orders is going to end, and that may be tough for your patients."

Not a Viable Future Strategy

Llamas recently consulted with Iris Plans, a telehealth-based advance care planning firm, regarding the future of opioid tele-prescribing.

"At Iris, we are doing (virtual) advance care planning for many patients, but some of them could also benefit from medical management," explained Bekanich, who is a cofounder of Iris Plans. "We wondered if there is a way we could start to do that via telehealth, in multiple states. But we wouldn't want to start a tele-palliative practice if we couldn't prescribe opioids remotely for seriously ill patients. After obtaining legal advice from Sarah (Llamas) we decided it won't be a viable business model."

Bekanich said his advocacy for tele-prescribing goes only as far as the population he normally sees, patients with a firmly established diagnosis of serious illness. Research suggests they are unlikely to become addicted to opioids in the absence of a prior history of opioid use disorder.

He is also familiar with the mitigation strategies of the addiction management field, such as urine drug screening and patient contracts aimed at minimizing the potential for abuse while still allowing for pain management -- which can be incorporated into virtual practice.

"For those facing serious illness who could benefit from opioids, I generally do not start with a urine drug screen. For me it's more about establishing trust and rapport, getting to a place of comfort with my patients where they'll talk honestly with me. I want that to be an open conversation, not punitive," he said, although in a small handful of cases something more prescriptive may be needed.

"The exception for telehealth should be made permanent, for the sake of the patients, not just the convenience of the prescriber," he added. "Telemedicine is an important capability to have for patients you haven't seen face-to-face, even though it's not for everyone. I worry about what happens after COVID. That creates a lot of uncertainty -- which is bad for our work."

https://www.medpagetoday.com/practicemanagement/telehealth/89881

Colchicine Approval Took a Huge Toll on CMS

 Colchicine, the old gout drug often cited as a cheap anti-inflammatory, hasn't been such a good deal since FDA approval, a study showed.

The inflation- and rebate-adjusted Medicaid price per pill jumped from $0.24 in 2008 to $4.20 after the FDA officially approved a branded form, Colcrys, through the agency's Unapproved Drug Initiative pathway in 2009.

As subsequent authorized generics emerged with only "marginally lower" prices, the price per pill actually rose further to $4.66 in 2015, reported Natalie McCormick, PhD, of Massachusetts General Hospital in Boston, and colleagues in JAMA Internal Medicine.

"Accordingly, Medicaid spending on single-ingredient colchicine rose 2833%," they wrote, and "58% of this increase was attributable to price increases alone."

Their study used Medicaid and Medicare data files through 2017, when combined Medicaid and Medicare claims exceeded $340 million for colchicine.

"Colcrys's manufacturer, which conducted a 1-week trial (n=185), received 3 years' market exclusivity for treatment of acute gout, and the unapproved formulations were soon ordered off the market, resulting in a virtual monopoly," McCormick's group noted.

"Furthermore, Colcrys was granted patents for this centuries-old drug until 2029. Thus, although more than six independent generics have FDA approval to date, only authorized generics with price points set by brand-name companies are currently available to treat acute gout, pericarditis, and now potentially millions with myocardial infarction" following the COLCOT trial.

The issue could gain even more relevance as colchicine looks promising for severe COVID-19. The drug has been added as a potential therapy for COVID-19 in the pragmatic RECOVERY trial that uncovered the survival benefit of dexamethasone.

"Only a fraction of an investment was required for Colcrys, a product that has provided no increased value and an unnecessary, long-term cost burden to the health care system," argued B. Joseph Guglielmo, PharmD, of the University of California San Francisco, in an accompanying editorial. "The current study findings illustrate that we can never allow such an egregious case to take place again."

Disclosures

McCormick reported grants from Canadian Institutes of Health Research.

Guglielmo disclosed no relevant relationships with industry.

Primary Source

JAMA Internal Medicine

Source Reference: McCormick N, et al "Prolonged increases in public-payer spending and prices after unapproved drug initiative approval of colchicine" JAMA Intern Med 2020; DOI: 10.1001/jamainternmed.2020.5017.

Secondary Source

JAMA Internal Medicine

Source Reference: Guglielmo BJ "The colchicine debacle revisited" JAMA Intern Med 2020; DOI: 10.1001/jamainternmed.2020.5044.

https://www.medpagetoday.com/rheumatology/generalrheumatology/89927

Possible benefit of regular use of potent mouthwashes in treatment of COVID-19

  

View ORCID ProfileKhalid Mukhtar, Suelen Qassim, Ibn-Masud Danjuma, Mohamed Elhassan Babiker, Mohamed Mohamedali, Housamaddeen Alfarhan, Abdel Rehim El-Tayeh, Mohammed Fakhri Khudhair, Muna Al.Maslamani, Mohammed Al-Dosari, Rumaisa Mohamed Elmustafa, Ahmed Hassib, Wesal Elhadary, Morwan Abdulkarim, Rajvir Singh

doi: https://doi.org/10.1101/2020.11.27.20234997

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.11.27.20234997v1.full.pdf

Abstract

As recently more in vitro studies demonstrated bactericidal and virucidal role for some of the over-the-counter mouthwash solutions. Meanwhile, Game theory and Evolutionary Biology suggests that inhibiting cooperation -reciprocal altruism- between two organisms can negatively affect their survival. Based on a set of relevant publications, it is proposed here that 2019-nCoV may be relying on a complicit; be it a certain organism (e.g. bacterial species), or a state of dysbiosis in general. On this premise, the regular use of potent disinfectant, (Hydrogen peroxide 2% and chlorhexidine gluconate mixed solution) for oral rinsing and gargling three times daily, through the repeated reduction in microbial load, was tested to determine whether it is able to induce a strain sufficient to inhibit reciprocal altruism, and hence halt the progression of the disease. through an RCT, (n = 93, intervention group: 47, control group: 46) the outcome tested in terms of in relation to the PCR/CT test of nasopharyngeal-oropharyngeal swabs from the baseline (at diagnosis), changes in the clinical category (improvement Vs. deterioration), and the final disposition (discharge Vs. Death) in different disease categories. Our findings showed, upon the regular use of mouthwash, more symptoms improvement after 2 days of treatment, higher rate of conversion to COVID19-negative PCR by 5 days of treatment, and less intubation and mortality, with all P-value < 0.05. There was also a trend of improvement in other outcome variables, though with no significant statistical difference; namely shorter hospital stay, less progression in Oxygen requirements, less rate of plasma transfusion, and extent of improvement in terms of disposition in relation to the clinical category on admission. were that can be justified by the complicit hypothesis, predict a rather preventive than therapeutic advantage, suggestive for a possible role for the regular use of potent mouthwash as an additional control measure in the community level.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

ISRCTN10197987 https://doi.org/10.1186/ISRCTN10197987

Funding Statement

The study is funded by Hamad Medical Corporation's Medical Research Center

https://www.medrxiv.org/content/10.1101/2020.11.27.20234997v1

BioNTech slips post-market following BofA downgrade

 

• BioNTech (NASDAQ:BNTX) falls as much as 4.4% after-hours as Bank of America advises investors to cash in profits from the stock's run higher, saying the company now faces heightened competition from peers that also are developing coronavirus vaccines.
• There's limited room for additional gains with the inevitable approval for the COVID-19 vaccine developed with partner Pfizer, which are now reflected in BNTX's 268% YTD rally, BofA analyst Tazeen Ahmad says in downgrading shares to Neutral from Buy with a $126 price target.
• https://seekingalpha.com/news/3640169-biontechminus-2-post-market-following-bofa-downgrade

Powell: 'Challenging' months until vaccine clears production, distribution hurdles

 A slowing recovery and a surging pandemic mean the United States is entering a “challenging” few months, with the potential deployment of a vaccine still facing the hurdles of production and mass distribution before its impact on the economy becomes clear, Fed chair Jerome Powell said on Monday.

“The rise in new COVID-19 cases, both here and abroad, is concerning and could prove challenging for the next few months,” Powell said in remarks prepared for delivery to a congressional hearing on Tuesday morning.

“Recent news on the vaccine front is very positive for the medium term. For now, significant challenges and uncertainties remain, including timing, production and distribution, and efficacy across different groups. It remains difficult to assess the timing and scope of the economic implications of these developments with any degree of confidence.”

Powell’s remarks are his most detailed yet on how the potential arrival of a vaccine may influence the Fed’s outlook, and the evolution of a recovery that the Fed chair acknowledged is slowing.

That, in turn, could shape opinions about how much more government support may be needed to help families and businesses bridge the gap between the current recession and the post-pandemic economy.

Vaccinations could begin before Christmas, U.S. Health Secretary Alex Azar said on Monday. [L1N2IG1LN]

In separate testimony to be delivered at the same hearing, Treasury Secretary Steven Mnuchin said the economy had made “remarkable progress” recovering ground lost due to the pandemic, and that any further government help should be targeted to “workers and small businesses that continue to struggle,” as opposed to spread broadly in the economy.

Mnuchin recently told the Fed to shut down several emergency lending programs, and suggested that $455 billion remaining for those facilities be reallocated for such a program.

With the vaccine on the horizon, some analysts say they expect a strong bounce in the economy in coming months as Americans are inoculated and broad immunity to the coronavirus is achieved.

However, Powell said the fate of the economy will remain hinged to the success of that process, and until then the impact of the pandemic will remain - and fall particularly hard on women, minority groups and those in the service sector.

“A full economic recovery is unlikely until people are confident that it is safe to re-engage in a broad range of activities,” Powell said.

https://www.reuters.com/article/us-usa-fed-powell/powell-challenging-months-until-vaccine-clears-production-distribution-hurdles-idUSKBN28A2ZS

COVID R&D Alliance launches trial of Amgen, UCB, Takeda drugs

 Amgen Inc, UCB SA and Takeda Pharmaceuticals Inc on Monday launched a global trial to identify whether any of three different drugs can reduce the severity of COVID-19 in hospitalized patients by moderating the immune system's response to the disease.

The drugmakers are part of the COVID Research & Development Alliance, a group of more than 20 pharmaceutical and biotechnology companies cooperating to speed development of therapies for the disease that has killed more than 1.4 million people worldwide.

The study initially will test whether Amgen’s psoriasis drug Otezla, Takeda’s experimental anti-inflammatory lanadelumab, and UCB's experimental immune system-inhibitor zilucoplan can prevent the body's own defenses from overreacting to the coronavirus, which can lead to serious, sometimes fatal, tissue and organ damage.

The three compounds "have a plausible biologic rationale in terms of effect on immune response or the hyper-immune response that some people develop," said Amgen research chief David Reese.

"We hope to find options that could potentially save lives ... before widespread availability of a vaccine,” he said.

Health experts do not expect vaccines to be available to most people until well into 2021. Meanwhile, COVID-19 hospitalizations are at record levels in the United States, threatening to overwhelm health systems.

The multiple candidates will be tested against a placebo with all trial patients also receiving standard care. Other drugs that work in a variety of ways, including antivirals, medicines that also modulate immune response and vascular agents may enter the study in coming months.

So far, only a generic class of steroids used since the 1960s to reduce inflammation in diseases such as arthritis has been shown in a controlled study to improve survival for severely ill hospitalized COVID-19 patients. Steroids are not recommended for patients with less severe illness.

The COVID R&D trial will enroll both hospitalized intensive care unit and non-ICU patients.

In anticipation of a rise and fall of COVID-19 cases in various geographic regions, the trial will include sites in the United States, Brazil, Mexico, Russia, South Africa and other countries.

“COVID is not confined to one country ... We have included a broad range of different countries," said Dhavalkumar Patel, UCB's chief scientific officer. 

https://www.marketscreener.com/quote/stock/AMGEN-INC-4847/news/COVID-R-D-Alliance-launches-trial-of-Amgen-UCB-Takeda-drugs-31903555/